Novel heterocyclic compounds as KIF18a inhibitors

Abstract

The present invention relates to novel heterocyclic compounds of Formula (I), (II), (III), or (IV) as inhibitors of KIF18A inhibitors, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, isotopes, prodrugs or deuterated compounds including their isotopes thereof The present invention also provides the process of preparing the said heterocyclic compounds of Formula (I), (II), (III), or (IV). (I) (II) (III) (IV)

Description

[0001] NOVEL HETEROCYCLIC COMPOUNDS AS KIF18A INHIBITORS RELATED PATENT APPLICATION: This application claims the priority to, and benefit of Indian Patent Application No.202441007105 filed on February 02, 2024, and Indian Patent Application No. 202441019102 filed on March 15, 2024; the disclosures of which are incorporated herein by reference. FIELD OF INVENTION: The present invention relates to novel heterocyclic compounds of formula (I), (II), (III) or (IV) as KIF18A inhibitors, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, isotopes, prodrugs or deuterated compounds including their isotopes thereof. (III) (IV) The present invention also relates to a process of manufacturing the novel heterocyclic compounds of Formula (I), (II), (III), and (IV). BACKGROUND OF THE INVENTION: The protein KIF18A inhibitor is a member of the kinesin superfamily and has been shown to participate in cell cycle and mitotic cell division. The function of KIF18A is to control chromosome aggregation and suppress centromere movements, and the main function is to regulate chromosome stability and maintain the oscillation attenuation of the mitotic spindle microtubule. Accurate alignment of chromosomes at the equator region and equal chromosome separation during cell division ensures maintenance of genome integrity (Scientific reports, 2013 Sep; 3(4): 2808). This is ensured by classes of motor proteins that are associated with actin filaments or microtubules (Cold Spring Harb Perspect Biol, 2017 May; 9(5): a025817). Kinesin superfamily comprises a class of microtubule associated molecular motors that obtain the energy to regulate the microtubule dynamics by an ATP hydrolysis method (Advances in protein chemistry, 2005; 71:299-234 & PNAS, 2017; 114:10894-899). KIF18A belongs to the kinesin-8 subfamily of motor proteins that is overexpressed in chromosomally unstable (CIN+ve) tumors (Frontier in Genetics, 2022 May; 13). It acts as a motile microtubule depolymerase required for chromosome congression (Current Biology, 2007 March; 17): 488-498). KIF18A regulates the growth of mitotic spindle length and depletion of KIF18A results in abnormally long spindles with lack of tension within sister kinetochores (Current Biology, 2018; September; 28: 2685–2696). Cells bearing chromosome instability (CIN+ve) are expected to be especially vulnerable to KIF18A inhibition as compared to CIN-ve population. KIF18A inhibition causes mitotic delay, cytostasis and eventual cell death particularly in CIN+ve cancer cells (Nature communications, 2021; 12:1213). Genetic and pharmacological pre-clinical studies suggest that non-cancerous chromosomally stable (CIN-ve) cells are not that much dependent on KIF18A for their survival and proliferation. This makes KIF18A an attractive anticancer therapy target for CIN+ve cancers and inhibitors are expected to have a wide therapeutic window with minimal toxic side effects. OBJECTIVE OF THE INVENTION: The primary objective of the present invention is to provide novel heterocyclic compounds as KIF18A inhibitors of Formula (I), (II), (III), or (IV). Another objective of the invention is to provide pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof, of the novel heterocyclic compounds of Formula (I), (II), (III), or (IV). Yet another objective of the present invention is to provide a process for the preparation of novel heterocyclic compounds of Formula (I), (II), (III) and (IV). Another objective of the present invention is to prepare a pharmaceutical composition comprising the heterocyclic compounds of Formula (I), (II), (III), or (IV). Yet another objective of the present invention is to provide a method of treating cancer by using the composition comprising novel heterocyclic compounds of Formula (I), (II), (III), or (IV). SUMMARY OF THE INVENTION: Accordingly, the present invention provides novel heterocyclic compounds of Formula (I), (II), (III) and (IV) as shown below: A compound of Formula (I)

[0002] wherein, X1 , X2 and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is selected from -NR8 1 - or -O-; L is selected from -NR8 8 8 8 2 SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof. A compound of Formula (II) wherein, X1 , X2 and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is selected from 8 1 -NR - or -O-; L is selected from -NR8SO -, -SO 8 8 8 22 2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof. A compound of formula (III) wherein, X1 , X2 , X3, X4 , X5, and X6 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is sele 8 1 cted from -NR - or -O-; L 8 8 8 8 2 is selected from -NR SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof. A compound of formula (IV) wherein, ring A is substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; X1 , X2 , X3, X4 , and X5 are each independently selected from N or CR5; L1is selected from -NR6- or -O-; L is selected from -NR7SO -, -SO NR7-, -NR7CO-, 7 22 2and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R5 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R6 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2 or 4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof. The compounds of formula (I), (II), (III) or (IV) or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof, wherein the compounds are selected from the group comprising of: N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- 1 yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide (S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin- 2 2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin- 3 2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(4-methyl-6,6a,7,8,9,10- 4 hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide N-(8,8-Difluoro-4-methyl-6,6a,7,8,9,10-hexahydrobenzo [b]pyrido 5 [1,2-d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl) sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide (S)-N-(6,6a,7,8,9,10-Hexahydrodipyrido[2,3-b:1',2'-d][1,4]oxazin- 6 2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide N-(8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- 7 d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide rel-(R)-N-(8,8-difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido 8 [1,2-d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide rel-(S)-N-(8,8-difluoro-6,6a,7,8,9,10-hexahydrobenzo[b] 9 pyrido[1,2-d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)- 2-(6-azaspiro[2.5]octan-6-yl)benzamide N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-4- 10 yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 11(S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin- 4-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin- 4-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-3- yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(6-oxo-6,6a,7,8,9,10-hexa hydro-5H-pyrido[1,2-a]quinoxalin-2-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxo-1',2'-dihydrospiro [cyclopentane-1,3'-pyrrolo[2,3-b]pyridin]-5'-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclohexane- 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclohexane- 1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1-methyl-2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclohexane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'-oxospiro [cyclohexane-1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 5-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-3-(6-azaspiro[2.5]octan-6-yl)picolinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6-yl)nicotinamide 28 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)nicotinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'oxospiro 29 [cyclopentane-1,3'-indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6- yl)nicotinamide N-(4-((6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin- 30 2-yl)amino)-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-7-yl)-2- hydroxyethane-1-sulfonamide N-(4-((8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- 31 d][1,4]oxazin-2-yl)amino)-5-(6-azaspiro[2.5]octan-6- yl)quinazolin-7-yl)-2-hydroxyethane-1-sulfonamide Further, the present invention also provides the process of preparing the compounds of Formula (I), (II), (III) and (IV) as below: A process for preparing heterocyclic compound of Formula (I) wherein, X1 , X2 and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L i 8 1 s selected from -NR - or -O-; L is selecte 8 8 8 8 2 d from -NR SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including isotopes thereof, comprising the step of: treating compound (23) with compound (4) wherein R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH- or with compound (6) wherein R2 is hydrogen, X1 and X2 are -CH- or with compound (12) wherein R2 is hydrogen, X1 and X2 are -CH-, Y is CH2- or -O-, n is 1 or 2 or with compound (14) wherein R2 is hydrogen, X1 and X2 are -CH-, Y is CH2- or -O-, n is 1 or 2 by using acid amine coupling reaction to give compounds of Formula (I). A process for preparation of intermediate compound (4) as above, comprising the steps of: i) reacting compound (1); with heterocycles in presence of base in a solvent to obtain compound (2); wherein R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH- ii) the compound (2) of step i) is treated in Buchwald–Hartwig amination reaction using a base and BINAP as ligand in presence of solvent and catalyst to obtain compound (3); and iii) compound (3) of step ii) upon nitro reduction provides compound (4) wherein, R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH-. wherein the base in step (i) is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate magnesium carbonate or mixtures thereof, wherein the preferred base is caesium carbonate. wherein the solvent in step (i) is selected from the group comprising acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, tetrahydrofuran, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof, wherein the preferred solvent is acetonitrile wherein the catalyst in step (ii) is selected from the group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis (triphenylphosphine)palladium(0) and tris(dibenzylideneacetone) dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). wherein the solvent in step (ii) is selected from a group comprising toluene, 1,2- dimethoxy ethane, diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, dioxane, methanol, DMSO, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof, wherein the preferred solvent is toluene. wherein the base in step (ii) is selected from a group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, ammonium hydroxide, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride or mixtures thereof, wherein the preferred base is sodium tertiary butoxide. A process for preparing intermediate compound (23) as above, comprising the steps of: i) treating a compound (19) with heterocycles in presence of base and a solvent to obtain compound (20); wherein R3 is heterocycle, ii) the compound of formula (20) obtained in the step (i) is further treated with suitable sulfonyl chloride in presence of a base and a solvent to obtain compound (21); and iii) the resulting compound (21) obtained in step (ii) is further hydrolyzed to get the compound (23). wherein the base in step (i) is selected from a group comprising sodium carbonate, sodium tertiary butoxide, sodium hydride, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, lithium hydride, magnesium carbonate or mixtures thereof, wherein the preferred base is potassium carbonate. wherein the solvent in step (i) is selected from the group comprising toluene, 1,2- dimethoxy ethane, tetrahydrofuran, diethyl ether, chlorinated solvent, acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, tetrahydrofuran, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof, wherein the preferred solvent is DMSO. wherein the base in step (ii) is selected from a group comprising triethyl amine, sodium carbonate, sodium tertiary butoxide, sodium hydride, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, lithium hydride, magnesium carbonate or mixtures thereof, wherein the preferred base is triethyl amine. wherein the solvent in step (ii) is selected from the group comprising toluene, 1,2- dimethoxy ethane, tetrahydrofuran, diethyl ether, chlorinated solvent, acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof, wherein the preferred solvent is tetrahydrofuran. A process for preparing heterocyclic compound of Formula (III) wherein, X1 , X2 , X3, X4 , X5, and X6 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is select 8 1 ed from -NR - or -O-; L is selected from -NR8SO -, -SO NR8-, -NR8CO-, and -CON 8 22 2R -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof, comprising the steps of: i) treating compound (25)

[0003] with compound (4) wherein, R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH- to obtain compound (26) ii) the compound (26) obtained in step i) is treated with sulfonamide in Buchwald condition followed by debenzylation to obtain the compounds of formula (III). wherein the acid in step i) is selected from the group comprising acetic acid, formic acid, citric acid, phosphoric acid, oxalic acid, nitric acid, wherein the preferred acid is acetic acid. wherein the sulfonamide in step ii) is selected from the group comprising sulfamethoxazole, sulfadoxine, sulfapyridine, sulfadiazine, 2-(benzyloxy) ethane- 1-sulfonamide or mixtures thereof, wherein the preferred sulfonamide is 2- (benzyloxy) ethane-1-sulfonamide. A process for preparing heterocyclic compound of Formula (IV) wherein, ring A is substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; X1 , X2 , X3, X4 , and X5 are each independently selected from N or CR5; L i 6 1 s selected from -NR - or -O-; L i 7 7 7 7 2 s selected from -NR SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R5 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R6 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2 or 4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof and comprising the step of: reacting compound (24); with compound (10), wherein R2 is hydrogen, X1 and X2 is -CH- or with compound (16), wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, or with compound (18), wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, to obtain the compound of Formula (IV). A process for preparing compound (10), comprising the steps of: i) treating compound (7) with heterocycles in presence of a suitable base to obtain compound (8) wherein R2 is hydrogen, X1 and X2 is -CH-; ii) treating compound (8) obtained in step i) in acidic condition to obtain compound (9); and iii) treating compound (9) with heterocycles in Buchwald condition using a base and BINAP as ligand in presence of a solvent and catalyst followed by reduction to obtain compound (10); wherein R2 is hydrogen, X1 and X2 is -CH-. wherein the base in step i) is selected from the group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, or sodium t-butoxide, wherein the preferred base is caesium carbonate or sodium t-butoxide. wherein the base in step iii) is selected from the group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium t-butoxide. wherein the solvent in step iii) is selected from the group comprising toluene, 1,2- dimethoxy ethane, diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, methanol, DMSO, dioxane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof, wherein the preferred solvent is toluene. wherein the catalyst in step iii) is selected from the group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf .CH2Cl2), Palladium(II) acetate ([Pd(OAc)2]n), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) or tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), wherein the preferred catalyst is Pd(OAc)2.A process of preparing compound (16) as above wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, comprising the reduction of compound (15) wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, to obtain compound (16). A process of preparing compound (18) as above wherein R is hydrogen, X1 and X2 is -CH-, n is 1 or 2, comprising the steps of: i) methylation of compound (15) in presence of a base; wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, to obtain compound (17) ii) reduction of compound (17) to obtain compound (18). The present invention also provides pharmaceutical composition comprising a compound of Formula (I), (II), (III) and (IV) or its pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, and a pharmaceutically acceptable excipients or carriers. The present invention also provides the use of a compound of Formula (I), (II), (III) and (IV) or its pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for manufacturing of medicament for a treatment of a cancer associated with KIF18A protein. The present invention also provides the use of a compound of Formula (I), (II), (III) and (IV) or its pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for a treatment of a cancer associated with KIF18A protein. The present invention also provides a method of treating cancer by administering to a subject therapeutically effective amount of a pharmaceutical composition comprising at least one or more of the compound of Formula (I), (II), (III) and (IV) or its pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein the subject has cancer. The said cancer is associated with KIF18A protein. Further, the cancer is a solid tumor or hematopoietic tumor: wherein the solid tumor is selected from but not limited to breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, stomach cancer, rhabdomyosarcoma, fibrosarcoma, thyroid follicular cancer or Kaposi's sarcoma, melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoactanthoma or uterine cancer. wherein the hematopoietic tumor is selected from but not limited to the group comprising: (a) a hematopoietic tumor of lymphoid lineage selected from leukemia, acute lymphocitic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell-20 lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma or Burkett's lymphoma; and (b) a hematopoietic tumor of myeloid lineage selected from acute and chronic myelogenous leukemias, myelodysplastic syndrome or promyelocytic leukemia. DETAILED DESCRIPTION OF THE INVENTION: Embodiments described herein can be understood more readily by reference to the following detailed description, examples, and tables. Numerous modifications and adaptations will be readily apparent to those skilled in the art without departing from the spirit and scope of the invention. Disclosed herein is the detailed description of the present invention pertaining to novel heterocyclic compounds of Formula (I), (II), (III) or (IV) and pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use of the novel heterocyclic compounds of Formula (I) or (II) or (III) or (IV). General terms used in Formula (I), (II), (III) or (IV) can be defined as follows; however, the meaning stated should not be interpreted as limiting the scope of the term per se. The term “halogen” or “halo” means fluorine or fluoro (F), chlorine or chloro (Cl), bromine or bromo (Br), or iodine or iodo (I). The term „alkyl‟ refers to an alkane derived hydrocarbon radical that includes solely carbon and hydrogen atoms in the backbone, contains no unsaturation, has carbon atoms from one to six, i.e. C1-6, preferably carbon atoms from one to four, i.e. C1-4, 10 and is attached to the remainder of the molecule by a single bond. Unless set forth or recited to the contrary, all alkyl groups described or claimed herein may be straight chain or branched, substituted or unsubstituted. When „alkyl‟ is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=O), CN, halogen, perhaloalkyl, cycloalkyl, substituted- or unsubstituted- aryl, substituted- or unsubstituted- heterocycle, -OR9b, -SO 9a 2R , - 9 N(alkyl)R , - N(H)C(=O)R9a, -N(H)R9, and -N(alkyl)R9; The term „carbocycle‟ or „cycloalkyl‟ refers to a non-aromatic mono or multicyclic ring system having 3 to 12 carbon atoms, i.e. C3-12, preferably carbon atoms from 3 to 6. Unless set forth or recited to the contrary, all cycloalkyl groups described or claimed herein may be substituted or unsubstituted. When „carbocycle‟ or „cycloalkyl‟ is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=O), CN, halogen, alkyl, perhaloalkyl, -OR9b, -SO 9a 9b 9a 9a 2R , -C(=O)OR , -OC(=O)R , -OC(=O)OR , - C(=O)N(H)R9, -C(=O)N(alkyl)R9, -N(H)C(=O)R9a, -N(H)R9, and -N(alkyl)R9; The term „heterocycle‟, unless otherwise specified, refers to substituted or unsubstituted non-aromatic 3- to 15- membered monocyclic / bicyclic / tricyclic ring which consists of carbon atoms and with one or more heteroatom(s) independently selected from N, O or S and unless stated otherwise specifically in the specification, the heterocycle may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include spiro or fused or bridged ring system. When „heterocycle‟ is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=O), CN, halogen, alkyl, perhaloalkyl, -OR9b, - CH -OR9b -C(=O)OR9b, -OC(=O)R9a, -OC 9a 9 2 , (=O)OR , -C(=O)N(H)R , - C(=O)N(alkyl)R9, -N(H)C(=O)R9a, -N(H)R9; The term „aryl‟, as used herein, refers to a monovalent monocyclic, bicyclic or tricyclic aromatic hydrocarbon ring system. Unless set forth or recited to the contrary, all aryl ring system described or claimed herein may be substituted or unsubstituted. When „aryl‟ group is substituted, it is substituted with 1 to 4 substituents selected from halogen, alkyl, CN, perhaloalkyl, cycloalkyl, -O-alkyl, -O-perhaloalkyl, -O- C(=O)-aryl, -N(alkyl)alkyl, -N(H)alkyl, -NH2, -N(alkyl)C(=O)alkyl, - N(H)C(=O)alkyl, -C(=O)N(alkyl)alkyl, -C(=O)N(H)alkyl, -C(=O)NH2, - SO2N(alkyl)alkyl, -SO2N(H)alkyl, -SO2NH2, -C(=O)OH, -C(=O)-alkyl, and - C(=O)O-alkyl; The term „heteroaryl‟, as used herein, refers to a 5-14 membered monocyclic, bicyclic, or tricyclic ring system having 1-4 ring heteroatoms selected from O, N, or S, and the remainder ring atoms being carbon (with appropriate hydrogen atoms unless otherwise indicated). When „heteroaryl‟ group is substituted, it is substituted with 1 to 4 substituents selected from halogen, alkyl, CN, perhaloalkyl, cycloalkyl, -O-alkyl, O- perhaloalkyl, -N(alkyl)alkyl, -N(H)alkyl, -NH2, -N(alkyl)C(=O)alkyl, - N(H)C(=O)alkyl, -C(=O)N(alkyl)alkyl, -C(=O)N(H)alkyl, -C(=O)NH2, - SO2N(alkyl)alkyl, -SO2N(H)alkyl, -SO2NH2, -C(=O)OH, -C(=O)-alkyl, and - C(=O)O-alkyl; each R9 is independently selected from hydrogen, alkyl, and cycloalkyl; each R9a is independently selected from alkyl, perhaloalkyl and cycloalkyl; each R9b is selected from hydrogen, alkyl, perhaloalkyl, and cycloalkyl. Accordingly in one aspect the present invention provides a novel heterocyclic compounds of Formula (I), (II), (III) and (IV) as a KIF18A inhibitor. According to one embodiment the present invention provides a compound of Formula (I):

[0004] or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including including their isotopes thereof, wherein: X1 , X2 and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is select 8 1 ed from -NR - or -O-; L is selected 8 8 8 8 2 from -NR SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4. In another embodiment, the present invention provides a compound of Formula (II), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including including their isotopes thereof, wherein: X1 , X2 and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L1is selected from -NR8- or -O-; L is selected from -NR8SO -, -SO NR8-, -NR8C 8 22 2O-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; In yet another embodiment, the present invention provides a compound of Formula (III), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including including their isotopes thereof, wherein: X1 , X2 , X3, X4 , X5, and X6 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L1is selected from -NR8- or -O-; L is selecte 8 8 8 8 2 d from -NR SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2;R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, - 2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; In yet another embodiment, the present invention provides compounds of Formula (IV), (IV) or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof, wherein; ring A is substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; X1 , X2 , X3, X4 , and X5 are each independently selected from N or CR5; L1is selected from -NR6- or -O-; L is selected from -NR7SO - 7 7 7 22, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, - 2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R5 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R6 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2 or 4. The particular compounds obtained from compound of Formula (I), (II), (III) or (IV) without departing from the scope of the definitions given under compounds of Formula (I) to (IV) are summarized herein below in Table 1 encompassing the entirety of the scope of compounds within compound of Formula (I) to (IV). Table 1: List of compounds of Formula (I), (II), (III) or (IV) with structures Example # Structure and IPAC name 1 N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 2 (S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 3 (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 4 4-((2-Hydroxyethyl)sulfonamido)-N-(4-methyl-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide N-(8,8-Difluoro-4-methyl-6,6a,7,8,9,10-hexahydrobenzo [b]pyrido[1,2-d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl) sulfonamido)-2-(6-azaspiro[2.5]octan-6-yl)benzamide (S)-N-(6,6a,7,8,9,10-Hexahydrodipyrido[2,3-b:1',2'-d][1,4] oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro [2.5]octan-6-yl)benzamide N-(8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide rel-(R)-N-(8,8-difluoro-6,6a,7,8,9,10-hexahydrobenzo [b] pyrido[1,2-d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl) sulfonamido)- 2-(6-azaspiro[2.5]octan-6-yl)benzamide rel-(S)-N-(8,8-difluoro-6,6a,7,8,9,10-hexahydrobenzo[b] pyrido[1,2-d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl) sulfonamido)- 2-(6-azaspiro[2.5]octan-6-yl)benzamide N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-4- yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro [2.5] octan-6- yl)benzamide (S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-4-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-4-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-3- yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5] octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(6-oxo-6,6a,7,8,9,10- hexahydro-5H-pyrido[1,2-a]quinoxalin-2-yl)-2-(6-azaspiro [2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro [cyclopentane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxo-1',2'- dihydrospiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridin]-5'-yl)-2- (6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclohexane - 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro [cyclopentane- 1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro [cyclohexane- 1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1-methyl-2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'-oxospiro [cyclopentane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'-oxospiro [cyclohexane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-7'-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclohexane-1,3'-indolin]-7'-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 5-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro [cyclopentane- 1,3'-indolin]-5'-yl)-3-(6-azaspiro[2.5]octan-6-yl)picolinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro [cyclopentane- 1,3'-indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6-yl)nicotinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro [cyclopentane- 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)nicotinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'-oxospiro [cyclopentane-1,3'-indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6- yl)nicotinamide 30 N-(4-((6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4] oxazin-2-yl)amino)-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-7- yl)-2-hydroxyethane-1-sulfonamide 31 N-(4-((8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido [1,2- d][1,4]oxazin-2-yl)amino)-5-(6-azaspiro[2.5]octan-6- yl)quinazolin-7-yl)-2-hydroxyethane-1-sulfonamide In another embodiment, the present invention provides the use of the compounds of Formula (I), (II), (III), or (IV) or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. Unless specifically indicated, the general Formula (I), (II), (III), or (IV) shall encompass tautomers and all stereo, optical and geometrical isomers (e.g. enantiomers, diastereomers, E / Z isomers, etc.) and racemates thereof as well as mixtures in different proportions of the separate enantiomers, mixtures of diastereomers, or mixtures of any of the foregoing forms where such isomers and enantiomers exist, as well as salts, including pharmaceutically acceptable salts thereof and solvates thereof such as for instance hydrates including solvates and hydrates of the free compound or solvates and hydrates of a salt of the compound. Compounds disclosed herein and their tautomeric forms, atropisomers, stereoisomers, prodrugs may be prepared, for example, by techniques well known in the organic synthesis and familiar to a practitioner ordinarily skilled in art of this invention. In addition, the processes described herein may enable the synthesis of the compounds of the present invention. However, these may not be the only means by which the compounds described in the invention may be synthesized. Further, the various synthetic steps described herein may be performed in alternate sequences to furnish the desired compounds. All isotopes of any particular atom or element as specified are contemplated within the scope of the compounds of the invention, and their uses. Exemplary isotopes that can be incorporated in to compounds of the invention include but are not limited to isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine and iodine, such as 2H (“D”), 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, 32P, 33P, 35S, 18F, 36Cl, 123I and 125I. The term “pharmaceutically acceptable salt” is taken to mean an active ingredient, which comprises a compound of the Formula (I), (II), (III), (IV) in the form of one of its salts, in particular if this salt form imparts improved pharmacokinetic properties on the active ingredient compared with the free form of the active ingredient or any other salt form of the active ingredient used earlier. The pharmaceutically acceptable salt form of the active ingredient can also provide this active ingredient for the first time with a desired pharmacokinetic property which it did not have earlier and can even have a positive influence on the pharmacodynamics of this active ingredient with respect to its therapeutic efficacy in the body. Compounds having basic amine groups can form pharmaceutically acceptable salts with pharmaceutically acceptable acid(s). Pharmaceutically acceptable salts of the compounds described herein include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Compounds disclosed herein and their tautomeric forms, atropisomers, stereoisomers, prodrugs may be prepared, for example, by techniques well known in the organic synthesis and familiar to a practitioner ordinarily skilled in art of this invention. In addition, the processes described herein may enable the synthesis of the compounds of the present invention. However, these may not be the only means by which the compounds described in the invention may be synthesized. Further, the various synthetic steps described herein may be performed in alternate sequences to furnish the desired compounds. The term “tautomer” or “tautomers” refers to the compounds of Formula (I), (II), (III), or (IV) of the present invention wherein any hydrogen atom is replaced by a hydroxyl group on a carbon with a double bond. The present invention includes all possible tautomeric forms. The term “prodrugs” refers to a compound having a group that can be converted into an amino group, a hydroxyl group, a carboxyl group, or the like, by solvolysis or under physiological conditions. Examples of the group for forming a prodrug include groups as described in Prog. Med., 5, 2157-2161 (1985). The present invention further provides a pharmaceutical composition comprising at one or more compound according to Formula (I), (II), (III), or (IV) or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, and a pharmaceutically acceptable excipient or carrier. "Pharmaceutically acceptable excipient" and "pharmaceutically acceptable carrier" refer to a substance that aids the formulation and / or administration of an active agent to and / or absorption by a subject and can be included in the compositions of the present disclosure without causing a significant adverse toxicological effect on the subject. Non-limiting examples of pharmaceutically acceptable carriers and / or diluents include water, NaCl, normal saline solutions, lactated Ringer's, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions, alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and / or aromatic substances and the like that do not deleteriously react with or interfere with the activity of the compounds provided herein. One of ordinary skill in the art will recognize that other pharmaceutical excipients are suitable for use with disclosed compounds. Disclosed herein are methods of treating a disease modulated at least in part by KIF18A in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, disclosed herein. A "subject" is a mammal, preferably a human, but can also be an animal in need of veterinary treatment, e.g., companion animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, sheep, pigs, horses, and the like) and laboratory animals (e.g., rats, mice, guinea pigs, and the like). Disclosed herein is a method of treating a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, disclosed herein. The present invention provides a compound described in the above aspect of the present invention or its tautomer, meso, racemate, enantiomer, and diastereomer, or the use of mixture forms thereof, or pharmaceutically acceptable salts thereof, for the preparation of medicaments for the prevention and / or treatment of KIF18A-mediated related diseases. The related disease mediated by KIF18A is an cancer selected from the group consisting of but not limited to (a) a solid or hematologically derived tumor selected from cancer of the bladder, endometrial, lung squamous cell, breast, colon, kidney, liver, lung, small cell lung cancer, esophagus, gall-bladder, brain, head and neck, ovary, pancreas, stomach, cervix, thyroid, prostate and skin, (b) a hematopoietic tumor of lymphoid lineage selected from leukemia, acute lymphocitic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell-20 lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma and Burkett's lymphoma, (c) a hematopoietic tumor of myeloid lineage selected from acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia (d) a tumor of mesenchymal origin selected from fibrosarcoma and rhabdomyosarcoma, (e) a tumor of the central and peripheral nervous system selected from astrocytoma, neuroblastoma, glioma and schwannoma, or (f) a melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoactanthoma, thyroid follicular cancer or Kaposi's sarcoma. Pharmaceutical formulations can be adapted for administration via any desired suitable method, for example by oral (including buccal or sublingual), rectal, nasal, topical (including buccal, sublingual or transdermal), vaginal or parenteral (including subcutaneous, intramuscular, intravenous or intradermal) methods. Such formulations can be prepared using all processes known in the pharmaceutical art by, for example, combining the active ingredient with the excipient(s) or adjuvant(s). Pharmaceutical formulations adapted for oral administration can be administered as separate units, such as, for example, capsules, tablets; powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; edible foams or foam foods; or oil-in-water liquid emulsions or water-in-oil liquid emulsions. For example, in the case of oral administration as tablet or capsule, the active- ingredient component can be combined with an oral, non-toxic and pharmaceutically acceptable inert excipient, such as, for example, ethanol, glycerol, water and the like. Powders are prepared by comminuting the compound to a suitable fine size and mixing it with a pharmaceutical excipient comminuted in a similar manner, such as, for example, an edible carbohydrate, such as, for example, starch or mannitol. A flavor, preservative, dispersant and dye may likewise be present. Capsules are produced by preparing a powder mixture as described above and filling shaped gelatine shells therewith. Glidants and lubricants, such as, for example, highly disperse silicic acid, talc, magnesium stearate, calcium stearate or polyethylene glycol in solid form can be added to the powder mixture before the filling operation. A disintegrant or solubilizer, such as, for example, agar-agar, calcium carbonate or sodium carbonate, may likewise be added in order to improve the availability of the medicament after the capsule has been taken. In addition, if desired or necessary, suitable binders, lubricants and disintegrants as well as dyes can likewise be incorporated into the mixture. Suitable binders include starch, gelatine, natural sugars, such as, for example, glucose or beta- lactose, sweeteners made from maize, natural and synthetic rubber, such as, for example, acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. The lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. The disintegrants include, without being restricted thereto, starch, methylcellulose, agar, bentonite, xanthan gum and the like. The tablets are formulated by, for example, preparing a powder mixture, granulating or dry pressing the mixture, adding a lubricant and a disintegrant and pressing the entire mixture to give tablets. A powder mixture is prepared by mixing the compound comminuted in a suitable manner with a diluent or a base, as described above, and optionally with a binder, such as, for example, carboxymethylcellulose, an alginate, gelatine or polyvinyl-pyrrolidone, a dissolution retardant, such as, for example, paraffin, an absorption accelerator, such as, for example, a quaternary salt, and / or an absorbant, such as, for example, bentonite, kaolin or dicalcium phosphate. The powder mixture can be granulated by wetting it with a binder, such as, for example, syrup, starch paste, acadia mucilage or solutions of cellulose or polymer materials and pressing it through a sieve. As an alternative to granulation, the powder mixture can be run through a tableting machine, giving lumps of non-uniform shape which are broken up to form granules. The granules can be lubricated by addition of stearic acid, a stearate salt, talc or mineral oil in order to prevent sticking to the tablet casting moulds. The lubricated mixture is then pressed to give tablets. The active ingredients can also be combined with a free-flowing inert excipient and then pressed directly to give tablets without carrying out the granulation or dry- pressing steps. A transparent or opaque protective layer consisting of a shellac sealing layer, a layer of sugar or polymer material and a gloss layer of wax may be present. Dyes can be added to these coatings in order to be able to differentiate between different dosage units. Oral liquids, such as, for example, solution, syrups and elixirs, can be prepared in the form of dosage units so that a given quantity comprises a pre-specified amount of the compounds. Syrups can be prepared by dissolving the compounds in an aqueous solution with a suitable flavour, while elixirs are prepared using a non- toxic alcoholic vehicle. Suspension can be formulated by dispersion of the compounds in a non-toxic vehicle. Solubilisers and emulsifiers, such as, for example, ethoxylated isostearyl alcohols and polyoxyethylene sorbitol ethers, preservatives, flavour additives, such as, for example, peppermint oil or natural sweeteners or saccharin, or other artificial sweeteners and the like, can likewise be added. The dosage unit formulations for oral administration can, if desired, be encapsulated in microcapsules. The formulation can also be prepared in such a way that the release is extended or retarded, such as, for example, by coating or embedding particulate material in polymers, wax and the like. Pharmaceutical compounds adapted for topical administration can be formulated as ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols or oils. Pharmaceutical formulations adapted for topical application to the eye include eye drops, in which the active ingredient is dissolved or suspended in a suitable carrier, in particular an aqueous solvent. Pharmaceutical formulations adapted for topical application in the mouth encompass lozenges, pastilles and mouthwashes. Pharmaceutical formulations adapted for rectal administration can be administered in the form of suppositories or enemas. Pharmaceutical formulations adapted for nasal administration in which the carrier substance is a solid comprising a coarse powder having a particle size, for example, in the range 20-500 microns, which is administered in the manner in which snuff is taken, i.e. by rapid inhalation via the nasal passages from a container containing the powder held close to the nose. Suitable formulations for administration as nasal spray or nose drops with a liquid as carrier substance encompass active-ingredient solutions in water or oil. Pharmaceutical formulations adapted for administration by inhalation encompass finely particulate dusts or mists, which can be generated by various types of pressurized dispensers with aerosols, nebulizers or inhalers. Pharmaceutical formulations adapted for vaginal administration can be administered as pessaries, tampons, creams, gels, pastes, foams or spray formulations. Pharmaceutical formulations adapted for parenteral administration include aqueous and non- aqueous sterile injection solutions comprising antioxidants, buffers, bacteriostatics and solutes, by means of which the formulation is rendered isotonic with the blood of the recipient to be treated; and aqueous and non-aqueous sterile suspensions, which may comprise suspension media and thickeners. The formulations can be administered in single-dose or multidose containers, for example sealed ampoules and vials, and stored in freeze-dried (lyophilized) state, so that only the addition of the sterile carrier liquid, for example water for injection purposes, immediately before use is necessary. Injection solutions and suspensions prepared in accordance with the recipe can be prepared from sterile powders, granules and tablets. In addition to the above particularly mentioned constituents, the formulations may also comprise other agents usual in the art with respect to the particular type of formulation; thus, for example, formulations which are suitable for oral administration may comprise flavors. A therapeutically effective amount of a compound of the Formula (I), or (II), or (III), or (IV) and of the other active ingredients depends on a number of factors, including, for example, the age and weight of the animal, the precise disease condition which requires treatment, and its severity, the nature of the formulation and the method of administration, and is ultimately determined by the treating doctor or vet. However, an effective amount of a compound is generally in the range from 0.1 to 100 mg / kg of body weight of the recipient (mammal) per day and particularly typically in the range from 1 to 10 mg / kg of body weight per day. Thus, the actual amount per day for an adult mammal weighing 70 kg is usually between 70 and 700 mg, where this amount can be administered as an individual dose per day or usually in a series of part-doses (such as, for example, two, three, four, five or six) per day, so that the total daily dose is the same. An effective amount of a salt or solvate or of a physiologically functional derivative thereof can be determined as the fraction of the effective amount of the compound per se. In further aspect, the present invention provides a process of preparing novel compound of Formula (I), (II), (III) and (IV). The novel heterocyclic compounds of Formula (I), (II), (III) and (IV) may be prepared using the following general method and procedures. It will be appreciated that where typical or preferred experimental conditions (i.e. reaction temperatures, time, moles of reagents, solvents etc.) are given, other experimental conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvents used, but such conditions can be determined by the person skilled in the art, using routine optimization procedures. Moreover, by utilizing the procedures described in detail, one of the ordinary skills in art can prepare additional compounds of the present invention claimed herein. All temperatures are in degrees Celsius (°C) unless otherwise noted. The processes described herein may enable the synthesis of the compounds of the present invention. However, these may not be the only means by which the compounds described in the invention may be synthesized. Further, the various synthetic steps described herein may be performed in alternate sequences to furnish the desired compounds. In one embodiment the present invention provides a process for preparing the compounds of Formula (I), (II), (III) or (IV), depicted in the Schemes given hereunder. One skilled-in-the-art will recognize that any of the Schemes can be adapted to produce the compounds of Formula (I), (II), (III) or (IV) and pharmaceutically acceptable salts of compounds of Formula (I), (II), (III) or (IV) according to the present invention. All symbols / variables are as defined hereunder unless otherwise stated. General methods: In one embodiment, the present invention provides process for preparing an intermediate compound (4) from compound (1) as precursor as shown in scheme 1 comprising the steps of: Scheme 1 Step i): The starting compound (1) was commercially available and was treated with heterocycles for example piperidin-2-ylmethanol in presence of a base to obtain compound (2). The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, or sodium t-butoxide wherein the preferred base is caesium carbonate or sodium t- butoxide. Step ii): The compound (2) was treated in acidic condition as known in the literature to deprotect Boc group to obtain the compound (3). Step iii): The compound (3) as obtained in the previous step was treated with heterocycles in Buchwald condition using a base and BINAP as ligand in a solvent and by using suitable catalyst followed by reduction using methods known in the art for nitro reduction to obtain compound (4). The catalyst used in the process is selected from a group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf .CH2Cl2), Palladium(II) acetate ([Pd(OAc)2]n), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) or tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), wherein the preferred catalyst is Pd(OAc)2. The said reaction is performed in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium t-butoxide. The reaction is carried out in presence of suitable solvent selected from group comprising toluene, 1,2-dimethoxy ethane, diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, methanol, DMSO, dioxane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol and diisopropyl ether. The preferred solvent is toluene. In another embodiment, the present invention provides process for preparing an intermediate compound (6) from compound (5) as shown in scheme 2 comprising the steps of: Scheme 2 The compound (5) was prepared as per procedures reported in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1988), (7), 1997-9; and was treated under reduction conditions using methods known in the art for nitro reduction to obtain compound (6). In another embodiment, the present invention provides process for preparing an intermediate i.e. compound (10) from compound (7) as shown in scheme 3 comprising the steps of: Scheme 3 Step i): The compound (7) was commercially available and was treated with heterocycles in presence of a suitable base to obtain compound (8). The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, or sodium t-butoxide wherein the preferred base is caesium carbonate or sodium t-butoxide. Step ii): The compound (8) was treated in acidic condition as known in the literature to deprotect Boc group to obtain the compound (9). Step iii): The compound (9) as obtained in the previous step was treated with heterocycles in Buchwald condition using a base and BINAP as ligand in a solvent and by using suitable catalyst followed by reduction using methods known in the art for nitro reduction to obtain compound (10). The catalyst used in the process is selected from a group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf .CH2Cl2), Palladium(II) acetate ([Pd(OAc)2]n), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) or tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), wherein the preferred catalyst is Pd(OAc)2. The said reaction is performed in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium t-butoxide. The reaction is carried out in presence of suitable solvent selected from group comprising toluene, 1,2-dimethoxy ethane, diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, methanol, DMSO, dioxane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof. The preferred solvent is toluene. In another embodiment, the present invention provides process for preparing an intermediate i.e. compound (12) and compound (14) from compound (11) as shown in scheme 4 comprising the steps of: Scheme 4 The compound (11) is prepared as per procedures reported in prior art WO201809650 or WO2019220101; and is treated under reduction conditions using methods known in the art for nitro reduction to obtain compound (12). Alternatively, compound (11) is methylated using base by methods known in the art to obtain compounds (13) which is further reduced using methods known in the art for nitro reduction to obtain compound (14). In further embodiment, the present invention provides process for preparing an intermediate i.e. compound (16) and compound (18) from compound (15) as shown in scheme 5 comprising the steps of:

[0005] Scheme 5 The compound (15) is prepared as per procedures reported in prior art WO2000066555; and was treated under reduction conditions using methods known in the art for nitro reduction to obtain compound (16). Alternatively, compound (15) is methylated using base by methods known in the art to obtain compound (17) which is further reduced using methods known in the art for nitro reduction to obtain compound (18). In yet another embodiment, the present invention provides a process for preparing an intermediate i.e. compound (23) from compound (19) as shown in scheme 6 comprising the steps of: Scheme 6 Step i): The compound (19), methyl 2-fluoro-4-nitrobenzoate is commercially available is treated with heterocycles in presence of base and a solvent for the aromatic nucleophilic displacement followed by nitro reduction to afford compound (20). The base used in the process is selected from a group comprising sodium carbonate, sodium tertiary butoxide, sodium hydride, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, lithium hydride and magnesium carbonate, wherein the preferred base is potassium carbonate. The solvent used in the reaction is selected from the group comprising toluene, 1,2- dimethoxy ethane, tetrahydrofuran, diethyl ether, chlorinated solvent, acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, tetrahydrofuran, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol and diisopropyl ether, wherein the preferred solvent is DMSO. Step ii): The resulting compound (20) as obtained in the previous step is coupled with suitable sulfonyl chloride in presence of a base and a solvent to afford compound (21). The said step is carried in presence of suitable base selected from group comprising triethyl amine, sodium carbonate, sodium tertiary butoxide, sodium hydride, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, lithium hydride and magnesium carbonate, wherein the preferred base is triethyl amine. The solvent used in the reaction is selected from the group comprising toluene, 1,2-dimethoxy ethane, tetrahydrofuran (THF), diethyl ether, chlorinated solvent, acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol and diisopropyl ether., wherein the preferred solvent is tetrahydrofuran. Step iii): The resulting compound (21) as obtained in step ii) was further hydrolyzed by the methods known in the art to obtain the compound (22). Step iv): The compound (22) is treated under hydrogenation condition by methods known in the art to obtain the compound (23). In another embodiment, the present invention provides process for preparing the compound of Formula (I) from compound (23) as shown in scheme 7 comprising the steps of: Scheme 7 The compounds (23) were treated with above-described intermediates i.e., compound (4) or (6) or (12) or (14) by using the methods known in the art for acid amine coupling reaction to give compounds of Formula (I). In another embodiment, the present invention provides process for preparing the compound of Formula (IV) from compound (24) as shown in scheme 8 comprising the steps of: Scheme 8 The compound (24) is treated with compound (10) or (16) or (18) by using the methods known in the art for acid amine coupling reaction to give compounds of Formula (IV). In further embodiment, the present invention provides process for preparing the compound of Formula (III) from compound (25) as shown in scheme 9 comprising the steps of: Scheme 9 Step i): The compound (25) as prepared using procedures reported in prior art WO2021026101; and was treated with compound (4) in presence of to obtain the compounds (26). The acid is selected from the group comprising acetic acid, formic acid, citric acid, phosphoric acid, oxalic acid, nitric acid, wherein the preferred acid is acetic acid. Step ii): The compound (26) as obtained in the previous step i) was treated with sulfonamide is selected from the group comprising sulfamethoxazole, sulfadoxine, sulfapyridine, sulfadiazine or 2-(benzyloxy) ethane-1-sulfonamide, wherein the preferred sulfonamide is 2-(benzyloxy) ethane-1-sulfonamide in Buchwald condition followed by debenzylation using hydrogenation condition by methods known in the art to obtain the compounds of formula (III). EXAMPLES Although the invention has been illustrated by certain of the preceding examples, it is not to be construed as being limited thereby; but rather, the invention encompasses the generic area as hereinbefore disclosed. Various modifications and embodiments can be made without departing from the spirit and scope thereof. Preparation 1: tert-Butyl 2-((2-bromo-4-nitrophenoxy)methyl)piperidine-1- carboxylate To a stirred solution of 2-bromo-1-fluoro-4-nitrobenzene (2.32g, 10.57mmol) in acetonitrile (10ml) was added tert-butyl-2-(hydroxymethyl)piperidine-1- carboxylate (2.5g, 11.62mmol) followed by cesium carbonate (6.85g, 21.09mmol) at 25°C. The resulting mixture was stirred at 80°C for 16h. The reaction mixture was diluted with water (50ml) and extracted with ethyl acetate (25ml x 2). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 3.8g of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 20% of ethyl acetate in hexane to afford the title compound (3.4g) as an off white solid. LCMS m / z = 315, 317 (100%). Preparation 2: tert-Butyl (S)-2-((2-bromo-4-nitrophenoxy)methyl)piperidine- 1-carboxylate The title compound was prepared by following same reaction protocol as described in the synthesis of tert-butyl 2-((2-bromo-4- nitrophenoxy)methyl)piperidine-1-carboxylate by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 3: tert-Butyl (R)-2-((2-bromo-4- nitrophenoxy)methyl)piperidine-1-carboxylate The title compound was prepared by following same reaction protocol as described in the synthesis of tert-butyl 2-((2-bromo-4- nitrophenoxy)methyl)piperidine-1-carboxylate by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 4: tert-Butyl (S)-2-(((3-bromo-5-nitropyridin-2- yl)oxy)methyl)piperidine-1-carboxylate The title compound was prepared by following same reaction protocol as described in the synthesis of tert-butyl 2-((2-bromo-4- nitrophenoxy)methyl)piperidine-1-carboxylate by using appropriate starting materials. LCMS m / z = 316, 318 (100%). Preparation 5: tert-Butyl 2-((2-bromo-4-nitrophenoxy)methyl)-4,4- difluoropiperidine-1-carboxylate The title compound was prepared by following same reaction protocol as described in the synthesis of tert-butyl 2-((2-bromo-4- nitrophenoxy)methyl)piperidine-1-carboxylate by using tert-butyl 4,4-difluoro-2- (hydroxymethyl)piperidine-1-carboxylate (synthesized as per the procedure reported in US20150051226 A1) as a starting material instead of tert-butyl-2- (hydroxymethyl)piperidine-1-carboxylate. LCMS m / z = 451, 453 (100%). Preparation 6: tert-Butyl 2-((2,6-dibromo-4-nitrophenoxy)methyl)piperidine- 1-carboxylate The title compound was prepared by following similar reaction protocol (25°C, 16h) as described in the synthesis of tert-butyl 2-((2-bromo-4-nitrophenoxy) methyl)piperidine-1-carboxylate by using appropriate starting materials. LCMS m / z = 393, 395, 397 (40%). Preparation 7: tert-Butyl 2-((2,6-dibromo-4-nitrophenoxy)methyl)-4,4- difluoropiperidine-1-carboxylate The title compound was prepared by following same reaction protocol as described in the synthesis of tert-butyl 2-((2-bromo-4- nitrophenoxy)methyl)piperidine-1-carboxylate by using tert-butyl 4,4-difluoro-2- (hydroxymethyl)piperidine-1-carboxylate (synthesized as per the procedure reported in US20150051226 A1) and 1,3-dibromo-2-fluoro-5-nitrobenzene. LCMS m / z = 528, 530 (100%). Preparation 8: tert-Butyl 2-((2-bromo-6-nitrophenoxy)methyl)piperidine-1- carboxylate To a stirred solution of 1-bromo-2-fluoro-3-nitrobenzene (0.2g, 0.9mmol) in acetonitrile (3ml) was added tert-butyl-2-(hydroxymethyl)piperidine-1- carboxylate (0.215g, 0.99mmol) followed by cesium carbonate (0.585g, 1.8mmol) at 25°C. The resulting mixture was stirred at 80°C for 16h. The reaction mixture was diluted with water (50ml) and extracted with ethyl acetate (25ml x 2). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.3g of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 20% of ethyl acetate in hexane to afford the title compound (0.2g) as an off white solid. LCMS m / z = 315, 317 (100%). Preparation 9: tert-Butyl (R)-2-((2-bromo-6- nitrophenoxy)methyl)piperidine-1-carboxylate The title compound was prepared by following same reaction protocol as described in the synthesis of tert-butyl 2-((2-bromo-6- nitrophenoxy)methyl)piperidine-1-carboxylate by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 10: tert-Butyl (S)-2-((2-bromo-6- nitrophenoxy)methyl)piperidine-1-carboxylate The title compound was prepared by following same reaction protocol as described in the synthesis of tert-butyl 2-((2-bromo-6- nitrophenoxy)methyl)piperidine-1-carboxylate by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 11: 2-((2-Bromo-4-nitrophenoxy)methyl)piperidine hydrochloride To a stirred solution of tert-butyl 2-((2-bromo-4-nitrophenoxy)methyl)piperidine- 1-carboxylate (1.7g) in dioxane (10ml) was added 4M HCl in dioxane (10ml) at 0°C. The resulting mixture was stirred at 25°C for 2h. The reaction mixture was concentrated in vacuo to give 1.5g of a crude compound, which was used for the next step without any purification. LCMS m / z = 315, 317 (100%). Preparation 12: (S)-2-((2-Bromo-4-nitrophenoxy)methyl)piperidine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 13: (R)-2-((2-Bromo-4-nitrophenoxy)methyl)piperidine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 14: (S)-3-Bromo-5-nitro-2-(piperidin-2-ylmethoxy)pyridine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 316, 318 (100%). Preparation 15: 2-((2-Bromo-4-nitrophenoxy)methyl)-4,4-difluoropiperidine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 351, 353 (100%). Preparation 16: 2-((2,6-Dibromo-4-nitrophenoxy)methyl)piperidine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 393, 395, 397 (100%). Preparation 17: 2-((2,6-Dibromo-4-nitrophenoxy)methyl)-4,4- difluoropiperidine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 429, 431, 433 (100%). Preparation 18: 2-((2-Bromo-6-nitrophenoxy)methyl)piperidine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 19: (R)-2-((2-Bromo-6-nitrophenoxy)methyl)piperidine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 20: (S)-2-((2-Bromo-6-nitrophenoxy)methyl)piperidine hydrochloride The title compound was prepared by following same reaction protocol as described in the synthesis of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride by using appropriate starting materials. LCMS m / z = 315, 317 (100%). Preparation 21: 2-Nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine To a stirred solution of 2-((2-bromo-4-nitrophenoxy)methyl)piperidine hydrochloride (0.4g, 1.26mmol) in toluene (8ml) was added cesium carbonate (1.43g, 4.41mmol) at 25°C. The resulting mixture was degassed by purging nitrogen gas for 10 mins. Palladium acetate (28.2mg, 0.126mmol) and BINAP (78.98mg, 0.126mmol) were then added to the reaction mixture and again degassed by purging nitrogen gas for 10 mins. The resulting mixture was stirred at 110°C for 16h. The reaction mixture was cooled to r.t. and filtered through celite bed under vacuum. The filtrate was diluted with ethyl acetate (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.38g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of ethyl acetate in hexane to afford the title compound (200mg) as an off white solid. LCMS m / z = 235 (100%) Preparation 22: (S)-2-Nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 235 (100%). Preparation 23: (R)-2-Nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 235 (100%). Preparation 24: 4-Bromo-2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 313, 315 (100%). Preparation 25: 4-Bromo-8,8-difluoro-2-nitro-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 350, 352 (100%). Preparation 26: (S)-2-Nitro-6,6a,7,8,9,10-hexahydrodipyrido[2,3-b:1',2'- d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 236 (100%). Preparation 27: 8,8-Difluoro-2-nitro-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 271 (100%). Preparation 28: 4-Nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 235 (100%) Preparation 29: (R)-4-Nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 235 (100%). Preparation 30: (S)-4-Nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 235 (100%). Preparation 4-Methyl-2-nitro-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazine In a sealed tube, a mixture of 4-bromo-2-nitro-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazine (0.9g, 2.89mmol) and K2CO3(1.198g, 8.69mmol) in dioxane / water (10ml, 7:3) was degassed with nitrogen gas for 15min. PdCl2dppf.CH2Cl2(236mg, 0.289mmol) and 50% trimethylboroxine in THF (396.8mg, 3.16mmol) were added and again degassed with nitrogen gas for 10min. The resulting mixture was stirred at 100°C for 16h. The reaction mixture was diluted with EtOAc (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.8g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (0.5g) as an off white solid. LCMS m / z = 249 (100%). Preparation 32: 8,8-Difluoro-4-methyl-2-nitro-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazine The title compound was prepared by following same reaction protocol as described in the synthesis of 4-Methyl-2-nitro-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazine by using appropriate starting materials. LCMS m / z = 285 (100%). Preparation 33: 6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- amine To a stirred solution of 2-nitro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazine (100mg, 0.426mmol) in methanol (8ml) was added nickel (II) chloride hexahydrate (10.14mg, 0.426mmol) followed by sodium borohydride (64.7mg, 1.704mmol) at 0°C. The resulting mixture was stirred at 0°C for 2h. The reaction mixture was quenched with sat.aq. NH4Cl (50ml) and stirred for 15-20 mins. Filtered the reaction mixture and filtrate was concentrated in vacuo to provide a residue, which was diluted with water (50ml) and extracted with ethyl acetate (25ml x 2). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 80mg of a crude compound as an off white solid. LCMS m / z = 205 (100%). Preparation 34: (S)-6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 205 (100%). Preparation 35: (R)-6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 205 (100%). Preparation 36: 4-Methyl-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 219 (100%). Preparation 37: 8,8-Difluoro-4-methyl-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 255 (100%). Preparation 38: (S)-6,6a,7,8,9,10-Hexahydrodipyrido[2,3-b:1',2'- d][1,4]oxazin-2-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 206 (100%). Preparation 39: 8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 241(100%). Preparation 39: 6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 205 (100%). Preparation 40: (R)-6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-4-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 205 (100%). Preparation 41: (S)-6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-4-amine The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 205 (100%). Preparation 42: 6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-3- amine The title compound was prepared by following same reaction protocol as described in WO2021043152 A1. Preparation 43: 2-Amino-7,8,9,10-tetrahydro-5H-pyrido[1,2-a]quinoxalin- 6(6aH)-one To a stirred solution of 2-nitro-7,8,9,10-tetrahydro-5H-pyrido[1,2-a]quinoxalin- 6(6aH)-one, which was synthesized as reported in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1988), (7), 1997-9; (240mg) in methanol (5ml) was added 10% Pd / C (100mg) at 25°C. The resulting mixture was stirred at 25°C for 16h under H2atmosphere with the help of balloon. Filtered the reaction mixture through celite bed under vacuum and the filtrate was concentrated in vacuo to provide 0.18g of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 50% of ethyl acetate in hexane to afford the title compound (100mg) as an off white solid. LCMS m / z = 218 (100%). Preparation 44: 5'-Nitrospiro[cyclopentane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in WO2018109650 A1. Preparation 45: 5'-Nitrospiro[cyclohexane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in WO2019220101. Preparation 46: 5'-Bromo-7'-nitrospiro[cyclopentane-1,3'-indolin]-2'-one To a stirred solution of 5'-bromospiro[cyclopentane-1,3'-indolin]-2'-one (synthesized as per WO2000066555 A1; 1g, 3mmol) in H2SO4(10ml) was added KNO3(417mg, 4mmol) at -10°C and stirred at 25°C for 2h. The reaction mixture was poured onto ice. The precipitated solid was filtered on Buchner funnel under vacuum, washed with water to afford 0.92g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (0.8g) as a pale brown solid. LCMS m / z = 311, 313 (100%) Preparation 47: 5'-Bromo-7'-nitrospiro[cyclohexane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 1'-methyl-5'-nitrospiro[cyclopentane-1,3'-indolin]-2'- one by using appropriate starting materials. LCMS m / z = 325, 327 (100%). Preparation 48: 5-Nitro-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]-2-one To a stirred solution of 2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]-2-one (1g) in H2SO4(10ml) was added KNO3(500mg) at 0°C and stirred for 1h. The reaction mixture was poured onto ice and made alkaline with aq.NH3. The precipitated solid was filtered on Buchner funnel under vacuum to afford 1.1g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (0.97g) as a yellow solid. LCMS m / z = 249 (100%) Preparation 49: 1'-Methyl-5'-nitrospiro[cyclopentane-1,3'-indolin]-2'-one To a stirred solution of 5'-nitrospiro[cyclopentane-1,3'-indolin]-2'-one (500mg, 2.15mmol) in DMF (3ml) was added NaH (103mg, 4.30mmol) at 0°C and stirred for 1h. Methyl iodide (0.147ml, 2.36mmol) was added thereto and stirred at 25°C for 16h. The reaction mixture was diluted with EtOAc (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.51g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (0.48g) as a yellow liquid. LCMS m / z = 247 (100%) Preparation 50: 1'-Methyl-5'-nitrospiro[cyclohexane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 1'-methyl-5'-nitrospiro[cyclopentane-1,3'-indolin]-2'- one by using appropriate starting materials. LCMS m / z = 261 (100%). Preparation 51: 1-Methyl-5-nitro-2',3',5',6'-tetrahydrospiro[indoline-3,4'- pyran]-2-one The title compound was prepared by following same reaction protocol as described in the synthesis of 1'-methyl-5'-nitrospiro[cyclopentane-1,3'-indolin]-2'- one by using appropriate starting materials. LCMS m / z = 263 (100%). Preparation 52: 5'-Bromo-1'-methyl-7'-nitrospiro[cyclopentane-1,3'-indolin]- 2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 1'-methyl-5'-nitrospiro[cyclopentane-1,3'-indolin]-2'- one by using appropriate starting materials. LCMS m / z = 325, 327 (100%). Preparation 53: 5'-Bromo-1'-methyl-7'-nitrospiro[cyclohexane-1,3'-indolin]- 2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 1'-methyl-5'-nitrospiro[cyclopentane-1,3'-indolin]-2'- one by using appropriate starting materials. LCMS m / z = 353, 355 (100%). Preparation 54: 5'-((Diphenylmethylene)amino)spiro[cyclopentane-1,3'- pyrrolo[2,3-b]pyridin]-2'(1'H)-one To a stirred solution of 5'-bromospiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridin]- 2'(1'H)-one (synthesized as per WO2020061377 A1; 100mg, 0.374mmol) in toluene (5ml) was added NaOtBu (72mg, 0.749mmol) at 25°C. The resulting mixture was degassed by purging nitrogen gas for 10 mins. Pd2dba3(35mg, 0.0374mmol) and BINAP (50mg, 0.0784mmol) were then added to the reaction mixture and again degassed by purging nitrogen gas for 10 mins. The resulting mixture was stirred at 110°C for 16h. The reaction mixture was cooled to r.t. and filtered through celite bed under vacuum. The filtrate was diluted with ethyl acetate (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 180mg of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 50% of ethyl acetate in hexane to afford the title compound (140mg) as an off white solid. LCMS m / z = 368 (100%) Preparation 55: 5'-Aminospiro[cyclopentane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 203 (100%). Preparation 56: 5'-Aminospiro[cyclohexane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 217 (100%). Preparation 57: 5-Amino-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]-2- one The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 219 (100%). Preparation 58: 5-Amino-1-methyl-2',3',5',6'-tetrahydrospiro[indoline-3,4'- pyran]-2-one The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 233 (100%). Preparation 59: 5'-Amino-1'-methylspiro[cyclopentane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 217 (100%). Preparation 60: 5'-Amino-1'-methylspiro[cyclohexane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 231 (100%). Preparation 61: 7'-Aminospiro[cyclopentane-1,3'-indolin]-2'-one To a stirred solution of 5'-bromo-7'-nitrospiro[cyclopentane-1,3'-indolin]-2'-one (800mg) in MeOH (50ml) was added Pd / C (5% wet, 300mg) at 25°C. The resulting mixture was stirred at 25°C for 16h under hydrogen atmosphere with balloon. The reaction mixture was filtered through celite under vacuum, washed with MeOH (50ml) and the filtrate was evaporated to provide 600mg of the crude compound as an off white solid. LCMS m / z = 281, 283 (100%). Preparation 62: 7'-Aminospiro[cyclohexane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 7'-aminospiro[cyclopentane-1,3'-indolin]-2'-one by using appropriate starting materials. LCMS m / z = 217 (100%). Preparation 63: 7'-Amino-1'-methylspiro[cyclopentane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 7'-aminospiro[cyclopentane-1,3'-indolin]-2'-one by using appropriate starting materials. LCMS m / z = 217 (100%). Preparation 64: 7'-Amino-1'-methylspiro[cyclohexane-1,3'-indolin]-2'-one The title compound was prepared by following same reaction protocol as described in the synthesis of 7'-aminospiro[cyclopentane-1,3'-indolin]-2'-one by using appropriate starting materials. LCMS m / z = 231 (100%). Preparation 65: 5'-Aminospiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridin]- 2'(1'H)-one To a stirred solution of 5'-((diphenylmethylene)amino)spiro[cyclopentane-1,3'- pyrrolo[2,3-b]pyridin]-2'(1'H)-one (140mg) in CH2Cl2(8ml) was added 4M HCl in dioxane (4.76ml) at 0°C. The resulting mixture was stirred at 25°C for 16h under N2atmosphere. The reaction mixture was diluted with Et2O (20ml) and washed with water (20ml). Layers were separated and the aqueous layer was basified with sat.aq.NaHCO3. This aqueous layer was extracted with CH2Cl2(20ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 130mg of a sufficiently pure compound, which was used “as is” for the next step. LCMS m / z = 204 (100%) Preparation 66: 4-Bromo-2-fluoro-6-(6-azaspiro[2.5]octan-6-yl)benzonitrile A solution of 4-bromo-2,6-difluorobenzonitrile (10g, 46mmol) and DIPEA (16mL, 92mmol) in DMSO (100mL) was cooled to 0°C and then treated with 6- azaspiro[2.5]octane (4.1g, 36.7 mmol). The reaction mixture was stirred at 25°C for 16h before it was diluted with water (100ml) and extracted with EtOAc (50ml x 2). The organic extracts were washed with brine (100ml), dried over Na2SO4, filtered, and concentrated in vacuo. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 50% of ethyl acetate in hexane to afford the title compound (12g, 85%) as an off white solid. LCMS m / z = 309, 311 (100%) Preparation 67: 4-Bromo-2-((2,4-dimethoxybenzyl)amino)-6-(6-azaspiro[2.5 ]octan-6-yl)benzonitrile

[0006] To a solution of 4-bromo-2-fluoro-6-(6-azaspiro[2.5]octan-6-yl)benzonitrile (1.0g, 3.2mmol) and DIPEA (1.13mL, 6.47mmol) in NMP (8mL) was added (2,4- dimethoxyphenyl)methanamine (0.52g, 3.10mmol) at 25°C and the resulting solution was heated at 120°C for 16h. The reaction mixture was diluted with water (50ml) and extracted with EtOAc (25ml x 2). The organic extracts were washed with brine (50ml), dried over Na2SO4, filtered, and concentrated in vacuo. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 60% of ethyl acetate in hexane to afford the title compound (1.05g, 71%) as a white solid. LCMS m / z = 456, 458 (100%) Preparation 68: 2-Amino-4-bromo-6-(6-azaspiro[2.5]octan-6-yl)benzonitrile A solution of 4-bromo-2-((2,4-dimethoxybenzyl)amino)-6-(6-azaspiro[2.5]octan- 6-yl)benzonitrile (1.0 g, 2.2 mmol) and anisole (0.60 mL, 5.48 mmol) in trifluoroacetic acid (5 mL) was stirred at 25°C for 16h. Then the reaction mixture was quenched with a satd. aq. sodium bicarbonate (50ml) and extracted with EtOAc (25ml x 2). The combined organic layer was washed with brine (50ml), dried over Na2SO4,filtered, and concentrated under reduced pressure. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of ethyl acetate in hexane to afford the title compound (610mg) as a pale yellow solid. LCMS m / z = 306, 308 (100%) Preparation 69: Ethyl (E)-N-(5-bromo-2-cyano-3-(6-azaspiro[2.5]octan-6- yl)phenyl)formimidate A solution of 2-amino-4-bromo-6-(6-azaspiro[2.5]octan-6-yl)benzonitrile (0.4g, 1.3mmol) in triethyl orthoformate (5 mL, 30 mmol) was treated with acetic anhydride (0.1 mL, 1.1 mmol) at 25°C and then heated at 145°C for 16h. Then the reaction mixture was concentrated under reduced pressure and ice-cold water was added to get a solid, which was filtered, to provide the title compound (0.4g, 85%) as a brown solid. The compound was directly taken without further purification. LCMS m / z = 334, 336 (100%) Preparation 70: Methyl 4-nitro-2-(6-azaspiro [2.5] octan-6-yl) benzoate To a stirred solution of methyl 2-fluoro-4-nitrobenzoate (2g, 0.010mol) in DMSO (20ml) was added 6-azaspiro [2.5] octane hydrochloride (1.48g, 0.010mol) and potassium carbonate (2.76g, 0.02mol) at 25°C. The resulting mixture was stirred at 80°C for 16h. The reaction mixture was quenched with ice cold water (100ml) and extracted with ethyl acetate (50ml x 2). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 2.32g of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 20% of ethyl acetate in hexane to afford the title compound (1.9g) as an orange liquid. LCMS m / z = 291 (100%). Preparation 71: Methyl 5-bromo-3-fluoropicolinate To a stirred solution of methyl 5-bromo-3-fluoropicolinate (1.55g, 6.618mmol) in DMF (8ml) was added potassium carbonate (977mg, 6.618mmol) and 6- azaspiro[2.5]octane (913mg, 6.618mmol) and the reaction mixture was stirred at 25°C for 16h. Then the reaction mixture was quenched with water (50ml) and extracted with EtOAc (20ml x 2). Layers were separated and the organic layer was washed with brine (50ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 2.1g of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 30% of ethyl acetate in hexane to afford the title compound (2g) as an off white solid. LCMS m / z = 325, 327 (100%). Preparation 72: Methyl 6-chloro-2-(6-azaspiro[2.5]octan-6-yl)nicotinate The title compound was prepared by following same reaction protocol as described in the synthesis of methyl 5-bromo-3-fluoropicolinate by using appropriate starting materials. LCMS m / z = 281, 283 (100%). Preparation 73: Methyl 6-chloro-4-(6-azaspiro[2.5]octan-6-yl)nicotinate To a stirred solution of methyl 4,6-dichloronicotinate (7g, 34.0 mmol) in DMF (70ml) was added potassium carbonate (4.7 g, 34.0 mmol) and 6- azaspiro[2.5]octane (3.8 g, 34.0 mmol) and the reaction mixture was stirred at 55°C for 16h. Then the reaction mixture was quenched with water (100ml) and extracted with EtOAc (50ml x 2). Layers were separated and the organic layer was washed with brine (20ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 6.7g of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 30% of ethyl acetate in hexane to afford the title compound (6.1g) as an off white solid. LCMS m / z = 281, 283 (100%). Preparation 74: Methyl 4-amino-2-(6-azaspiro [2.5] octan-6-yl)benzoate To a stirred solution of methyl 4-nitro-2-(6-azaspiro[2.5] octan-6-yl) benzoate (2g, 6.8mmol) in methanol (20ml) was added nickel (II) chloride hexahydrate (161.6mg, 0.68mmol) followed by sodium borohydride (781.8mg, 20mmol) at 0°C. The resulting mixture was stirred at 0°C for 1h. The reaction mixture was quenched with sat.aq.ammonium chloride (50ml) and stirred for 15-20 mins. Filtered the reaction mixture and filtrate was concentrated in vacuo to provide a residue, which was diluted with water (50ml) and extracted with ethyl acetate (25ml x 2). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1.8g of a crude compound as an orange liquid. LCMS m / z = 261 (100%). Preparation 75: Methyl 4-((2-(benzyloxy) ethyl) sulfonamido)-2-(6-azaspiro [2.5]octan-6-yl)benzoate To a stirred solution of methyl 4-amino-2-(6-azaspiro [2.5] octan-6-yl) benzoate (1.8g, 6.91mol) in THF (20ml) was added triethylamine (2.89ml, 20.73mol) followed by 2-(benzyloxy)ethane-1-sulfonyl chloride (1.94g, 8.29mol) at 25°C. The resulting mixture was stirred at 100°C for 16h. The reaction mixture was concentrated in vacuo to provide a residue, which was diluted with ethyl acetate (50ml) and washed with brine (20ml). Layers were separated and the organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1.3g of a crude compound as an orange liquid. LCMS m / z = 459 (100%). Preparation 76: 4-((2-(Benzyloxy) ethyl) sulfonamido)-2-(6-azaspiro [2.5]octan-6-yl)benzoic acid To a stirred solution of methyl 4-((2-(benzyloxy) ethyl) sulfonamido)-2-(6- azaspiro [2.5]octan-6-yl) benzoate (1.3g, 0.28mmol) in THF (6ml) and methanol (6ml) was added lithium hydroxide monohydrate (357.3mg, 0.85mmol) in water (6ml) at rt. The resulting mixture was stirred at 80°C for 16h. The reaction mixture was concentrated in vacuo to provide a residue, which was acidified with 1N HCl (50ml) and extracted with ethyl acetate (50ml). Layers were separated and the organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.8g of a crude compound as a brown solid. LCMS m / z = 355 (100%). Preparation 77: 4-((2-Hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzoic acid To a stirred solution of 4-((2-(benzyloxy) ethyl) sulfonamido)-2-(6-azaspiro [2.5]octan-6-yl)benzoic acid (500mg, 1.091mmol) in methanol (6ml) was added wet 10% palladium on carbon (350mg) at 25°C. The resulting mixture was stirred under H2atmosphere with the help of balloon at 25°C for 48h. The resulting mixture was filtered through celite and the filtrate was concentrated in vacuo to give 300mg of a crude compound as an off white solid. LCMS m / z = 355 (10%). Preparation 78: Methyl 5-((2-hydroxyethyl)sulfonamido)-3-(6- azaspiro[2.5]octan-6-yl)picolinate A mixture of methyl 5-bromo-3-(6-azaspiro[2.5]octan-6-yl)picolinate (1.5g, 4.63mmol), 2-hydroxyethane-l-sulfonamide (1.15g, 9.23mmol) K3PO4(2.93g, 13.84mmol), (1R,2R)-N1,N2-dimethylcyclohexane-1.2-diamine (656mg, 4.61mmol) and copper (I) iodide (1.75g, 9.23mmol) in DMF (15mL) was heated at 90°C for 16h. Then the reaction mixture was filtered through a plug of celite and the filter cake was rinsed with 2 x 50ml of EtOAc. The filtrate was washed with water (50ml) followed by brine (50ml), dried over Na2SO4,filtered and concentrated. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 50% of ethyl acetate in hexane to afford the title compound (230mg) as an off white solid. LCMS m / z = 370 (100%). Preparation 79: 5-((2-Hydroxyethyl)sulfonamido)-3-(6-azaspiro[2.5]octan-6- yl)picolinic acid To a stirred solution of methyl 5-((2-hydroxyethyl)sulfonamido)-3-(6- azaspiro[2.5]octan-6-yl)picolinate (230mg, 0.623mmol) in methanol (4ml) was added NaOH (49.8mg, 1.246mmol) in water (4ml) at rt. The resulting mixture was stirred at 50°C for 16h. The reaction mixture was concentrated in vacuo to provide a residue, which was acidified with 1N HCl (50ml) and extracted with ethyl acetate (50ml). Layers were separated and the organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 140mg of a crude compound as a brown solid. LCMS m / z = 356 (100%). Preparation 80: 6-Chloro-4-(6-azaspiro[2.5]octan-6-yl)nicotinic acid To a stirred solution of methyl 6-chloro-4-(6-azaspiro[2.5]octan-6-yl)nicotinate (5g, 17.8mmol) in water (35ml) and THF (15ml) was added LiOH.H2O (1.3g, 53.4mmol) and the reaction mixture was stirred at 60°C for 6h. Then the reaction mixture was quenched with 1N HCl (100ml) and extracted with EtOAc (50ml x 2). Layers were separated and the organic layer was washed with brine (20ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 5g of a crude compound as an off white solid, which was directly used in the next step LCMS m / z = 267 (100%). Preparation 81: 6-Chloro-2-(6-azaspiro[2.5]octan-6-yl)nicotinic acid The title compound was prepared by following same reaction protocol as described in the synthesis of 6-chloro-4-(6-azaspiro[2.5]octan-6-yl)nicotinic acid by using appropriate starting materials. LCMS m / z = 267 (100%). Preparation 82: 6-Chloro-N-(2'-oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-4- (6-azaspiro[2.5]octan-6-yl)nicotinamide To a stirred solution of 6-chloro-4-(6-azaspiro[2.5]octan-6-yl)nicotinic acid (200mg, 0.74mmol) in DMF (3ml) was added DIPEA (0.31ml, 1.85mmol) and HATU (422mg, 1.11mmol) followed by 5'-aminospiro[cyclopentane-1,3'- indolin]-2'-one (152mg, 0.74mmol) at 0°C. The resulting mixture was stirred at 25°C for 16h. The residue was quenched with water (50ml) and extracted with ethyl acetate (50ml). Layers were separated and the organic layer was washed with brine (30ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 280mg of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 50% of ethyl acetate in hexane to afford the title compound (200mg) as an off white solid. LCMS m / z = 265, 267 (100%). Preparation 83: 6-Chloro-N-(1'-methyl-2'-oxospiro[cyclopentane-1,3'- indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6-yl)nicotinamide The title compound was prepared by following same reaction protocol as described in the synthesis of 6-chloro-N-(2'-oxospiro[cyclopentane-1,3'-indolin]- 5'-yl)-4-(6-azaspiro[2.5]octan-6-yl)nicotinamide by using appropriate starting materials. LCMS m / z = 218 (100%). Preparation 84: 6-Chloro-N-(2'-oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-2- (6-azaspiro[2.5]octan-6-yl)nicotinamide The title compound was prepared by following same reaction protocol as described in the synthesis of 6-chloro-N-(2'-oxospiro[cyclopentane-1,3'-indolin]- 5'-yl)-4-(6-azaspiro[2.5]octan-6-yl)nicotinamide by using appropriate starting materials. LCMS m / z = 267, 269 (100%). Preparation 85: N-(7-bromo-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-4-yl)- 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-amine A solution of ethyl (E)-N-(5-bromo-2-cyano-3-(6-azaspiro[2.5]octan-6- yl)phenyl)formimidate (0.3g, 0.828mmol) and 6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-amine (0.169g, 0.828mmol) in acetic acid (3 mL) was heated at 125°C for 1h. The resulting mixture was diluted with water (50ml) and extracted with ethyl acetate (50ml). Layers were separated and the organic layer was washed with brine (30ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 280mg of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 30% of ethyl acetate in hexane to afford the title compound (200mg) as an off-white solid LCMS m / z = 520, 522 (50%) Preparation 86: N-(7-bromo-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-4-yl)- 8,8-difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- amine The title compound was prepared by following same reaction protocol as described in the synthesis of N-(7-bromo-5-(6-azaspiro[2.5]octan-6-yl)quinazolin- 4-yl)-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-amine by using appropriate starting materials. LCMS m / z = 556, 558 (100%). Examples Example 1: N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6-yl)benzamide To a stirred solution of 4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan- 6-yl)benzoic acid (100mg, 0.282mmol) in DMF (4ml) was added DIPEA (0.13ml, 0.790mmol) and HATU (128.8mg, 0.338mmol) followed by 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-amine (57.6mg, 0.282mmol) at 0°C. The resulting mixture was stirred at 25°C for 16h. The residue was quenched with water (50ml) and extracted with ethyl acetate (50ml). Layers were separated and the organic layer was washed with brine (30ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 95mg of a crude compound. This crude residue was purified by combi-flash instrument onto a redisep® column with a gradient elution of 0 to 50% of ethyl acetate in hexane to afford the title compound (16mg) as an off white solid. 1H NMR (400MHz, DMSO-d6) δ: 11.49 (s, 1H), 10.07 (brs, 1H), 7.82 (d, J= 7.6Hz, 1H), 7.36 (s, 1H), 7.15 (s, 1H), 7.04-6.97 (m, 2H), 6.66 (d, J=7.6Hz, 1H), 4.95 (brs, 1H), 4.18-4.13 (m, 1H), 3.89-3.82 (m, 1H), 3.77-3.69 (m, 2H), 3.33-3.29 (m, 4H), 2.96-2.94 (m, 4H), 2.59-2.54 (m, 1H), 1.82-1.74 (m, 2H), 1.67-1.62 (m, 1H), 1.60-1.39 (m, 6H), 1.24-1.14 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 271 (100%). Example 2: (S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin- 2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.51 (s, 1H), 10.10 (brs, 1H), 7.82 (d, J= 7.6Hz, 1H), 7.36 (s, 1H), 7.15 (s, 1H), 7.04-6.97 (m, 2H), 6.66 (d, J=7.6Hz, 1H), 4.95 (brs, 1H), 4.18-4.13 (m, 1H), 3.89-3.82 (m, 1H), 3.77-3.69 (m, 2H), 3.33-3.29 (m, 4H), 2.96-2.94 (m, 4H), 2.59-2.54 (m, 1H), 1.82-1.74 (m, 2H), 1.67-1.62 (m, 1H), 1.60-1.39 (m, 6H), 1.24-1.14 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 271 (100%). Example 3: (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin- 2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.51 (s, 1H), 10.10 (brs, 1H), 7.82 (d, J= 7.6Hz, 1H), 7.36 (s, 1H), 7.15 (s, 1H), 7.04-6.97 (m, 2H), 6.66 (d, J=7.6Hz, 1H), 4.95 (brs, 1H), 4.18-4.13 (m, 1H), 3.89-3.82 (m, 1H), 3.77-3.69 (m, 2H), 3.33-3.29 (m, 4H), 2.96-2.94 (m, 4H), 2.59-2.54 (m, 1H), 1.82-1.74 (m, 2H), 1.67-1.62 (m, 1H), 1.60-1.39 (m, 6H), 1.24-1.14 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 271 (100%). Example 4: 4-((2-Hydroxyethyl)sulfonamido)-N-(4-methyl-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.44 (s, 1H), 10.07 (brs, 1H), 7.81 (d, J= 8.8Hz, 1H), 7.20-7.07 (m, 2H), 7.06-6.98 (m, 2H), 4.95 (brs, 1H), 4.23-4.16 (m, 1H), 3.92-3.82 (m, 1H), 3.77-3.69 (m, 2H), 3.33-3.29 (m, 4H), 2.96-2.94 (m, 4H), 2.59-2.54 (m, 1H), 2.07 (s, 3H), 1.82-1.74 (m, 2H), 1.67-1.62 (m, 1H), 1.60-1.39 (m, 6H), 1.24-1.14 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 278 (100%). Example 5: N-(8,8-Difluoro-4-methyl-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl) sulfonamido)-2-(6-azaspiro[2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.34 (s, 1H), 10.07 (brs, 1H), 7.82-7.77 (m, 1H), 7.24-7.12 (m, 2H), 7.06-6.98 (m, 2H), 4.95 (brs, 1H), 4.33-4.26 (m, 1H), 4.05- 3.95 (m, 1H), 3.95-3.85 (m, 1H), 3.80-3.70 (m, 2H), 3.33-3.29 (m, 4H), 3.00-2.95 (m, 4H), 2.90-2.80 (m, 1H), 2.59-2.54 (m, 1H), 2.20-2.10 (m, 2H), 2.07 (s, 3H), 1.60-1.50 (m, 4H), 0.40-0.30 (m, 4H); LCMS m / z = 296 (100%). Example 6: (S)-N-(6,6a,7,8,9,10-Hexahydrodipyrido[2,3-b:1',2'-d][1,4]oxazin- 2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.46 (s, 1H), 10.10 (brs, 1H), 7.85-7.75 (m, 2H), 7.73-7.69 (m, 1H), 7.20-7.10 (m, 1H), 7.05-6.98 (m, 1H), 4.95 (brs, 1H), 4.32- 4.26 (m, 1H), 4.05-3.95 (m, 1H), 3.80-3.70 (m, 2H), 3.70-3.65 (m, 1H), 3.65-3.55 (m, 2H), 3.00-2.90 (m, 4H), 2.59-2.54 (m, 1H), 1.85-1.65 (m, 4H), 1.60-1.50 (m, 4H), 1.45-1.30 (m, 2H), 1.20-1.10 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 540 (100%). Example 7: N-(8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.41 (s, 1H), 10.07 (s, 1H), 7.82 (d, J= 8.4Hz, 1H), 7.59-7.39 (m, 1H), 7.35-7.25 (m, 1H), 7.04-6.97 (m, 2H), 6.64 (d, J=8.4Hz, 1H), 4.95 (brs, 1H), 4.30-4.24 (m, 1H), 4.05-3.85 (m, 2H), 3.80-3.70 (m, 2H), 3.34-3.29 (m, 3H), 3.00-2.80 (m, 5H), 2.25-2.10 (m, 2H), 2.10-1.70 (m, 2H), 1.60-1.45 (m, 4H), 0.35-0.2 (m, 4H); LCMS m / z = 279 (100%). This racemic compound (example 7) was purified by chiral preparative HPLC to give two enantiomers (example 8 & 9) as shown below as, Example 8: 1H NMR (400MHz, DMSO-d6) δ: 11.59 (s, 1H), 10.07 (s, 1H), 7.82 (d, J= 8.4Hz, 1H), 7.59-7.39 (m, 1H), 7.35-7.25 (m, 1H), 7.04-6.97 (m, 2H), 6.64 (d, J=8.4Hz, 1H), 4.95 (brs, 1H), 4.30-4.24 (m, 1H), 4.05-3.85 (m, 2H), 3.80-3.70 (m, 2H), 3.34-3.29 (m, 3H), 3.00-2.80 (m, 5H), 2.25-2.10 (m, 2H), 2.10-1.70 (m, 2H), 1.60-1.45 (m, 4H), 0.35-0.2 (m, 4H);LCMS m / z = 577 (100%). Example 9: 1H NMR (400MHz, DMSO-d6) δ: 11.42 (s, 1H), 10.07 (s, 1H), 7.82 (d, J= 8.4Hz, 1H), 7.59-7.39 (m, 1H), 7.35-7.25 (m, 1H), 7.04-6.97 (m, 2H), 6.64 (d, J=8.4Hz, 1H), 4.95 (brs, 1H), 4.30-4.24 (m, 1H), 4.05-3.85 (m, 2H), 3.80-3.70 (m, 2H), 3.34-3.29 (m, 3H), 3.00-2.80 (m, 5H), 2.25-2.10 (m, 2H), 2.10-1.70 (m, 2H), 1.60-1.45 (m, 4H), 0.35-0.2 (m, 4H);LCMS m / z = 577 (100%). Example 10: N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-4- yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.44 (s, 1H), 10.10 (s, 1H), 7.94 (t, J= 8.8Hz, 2H), 7.17 (d, J= 2Hz, 1H), 7.02 (dd, J=8.6Hz, 2.0Hz, 1H), 6.76 (t, J=8.0Hz, 1H), 6.68-6.64 (m 1H), 4.95 (brs, 1H), 4.35-4.30 (m, 1H), 4.03-3.96 (m, 1H), 3.88-3.83 (m, 1H), 3.77-3.72 (m, 2H), 3.62-3.58 (m, 1H), 3.04-2.85 (m, 5H), 1.85-1.78 (m, 1H), 1.75-1.65 (m, 3H), 1.65-1.40 (m, 6H), 1.30-1.15 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 271 (100%). Example 11: (S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-4-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.44 (s, 1H), 10.10 (s, 1H), 7.94 (t, J= 8.8Hz, 2H), 7.17 (d, J= 2Hz, 1H), 7.02 (dd, J=8.6Hz, 2.0Hz, 1H), 6.76 (t, J=8.0Hz, 1H), 6.68-6.64 (m 1H), 4.95 (brs, 1H), 4.35-4.30 (m, 1H), 4.03-3.96 (m, 1H), 3.88-3.83 (m, 1H), 3.77-3.72 (m, 2H), 3.04-2.85 (m, 6H), 1.83-1.78 (m, 1H), 1.75-1.65 (m, 3H), 1.65-1.40 (m, 6H), 1.30-1.15 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 271 (100%). Example 12: (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-4-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan- 6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.44 (s, 1H), 10.10 (s, 1H), 7.94 (t, J= 8.8Hz, 2H), 7.17 (d, J= 2Hz, 1H), 7.02 (dd, J=8.6Hz, 2.0Hz, 1H), 6.76 (t, J=8.0Hz, 1H), 6.68-6.64 (m 1H), 4.95 (brs, 1H), 4.35-4.30 (m, 1H), 4.03-3.96 (m, 1H), 3.88-3.83 (m, 1H), 3.77-3.72 (m, 2H), 3.04-2.85 (m, 6H), 1.83-1.78 (m, 1H), 1.75-1.65 (m, 3H), 1.65-1.40 (m, 6H), 1.30-1.15 (m, 1H), 0.40-0.30 (m, 4H); LCMS m / z = 271 (100%). Example 13: N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-3- yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.37 (s, 1H), 10.07 (s, 1H), 7.82 (d, J= 8.8Hz, 1H), 7.25-7.20 (m, 1H), 7.16-7.14 (m, 1H), 7.12-7.07 (m, 1H), 7.04-6.98 (m, 1H), 6.90-6.85 (m, 1H), 4.90 (brs, 1H), 4.22-4.15 (m, 1H), 3.95-3.84 (m, 1H), 3.85-- 3.72 (m, 3H), 3.00-2.90 (m, 6H), 2.59-2.40 (m, 2H), 1.82-1.70 (m, 2H), 1.68-1.62 (m, 1H), 1.60-1.45 (m, 5H), 1.44-1.32 (m, 1H), 1.20-1.08 (m, 1H), 0.3-0.25 (m, 4H); LCMS m / z = 541 (100%). Example 14: 4-((2-Hydroxyethyl)sulfonamido)-N-(6-oxo-6,6a,7,8,9,10- hexahydro-5H-pyrido[1,2-a]quinoxalin-2-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials. 1H NMR (400MHz, DMSO-d6) δ: 11.64 (s, 1H), 10.36 (s, 1H), 7.83 (d, J= 7.6Hz, 1H), 7.30-7.28 (m, 1H), 7.18-7.14 (m, 2H), 7.02 (d, J=7.2Hz, 1H), 6.66 (d, J=8.0Hz, 1H), 5.00 (brs, 1H), 3.77-3.73 (m, 2H), 3.68-3.65 (m, 1H), 3.52-3.49 (m, 1H), 2.98-2.94 (m, 5H), 2.77-2.75 (m, 1H), 1.98-1.83 (m, 3H), 1.66-1.46 (m, 9H), 1.45-1.23 (m, 4H); LCMS m / z = 554 (100%). Example 15: 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.65 (s, 1H), 10.28 (s, 1H), 10.08 (s, 1H), 7.83 (d, J= 8.4Hz, 1H), 7.67 (d, J= 1.6Hz, 1H), 7.57 (dd, J= 8.4Hz , 2Hz, 1H), 7.16 (d, J= 2Hz, 1H), 7.03 (dd, J= 8.6Hz , 2Hz, 1H), 6.83 (d, J= 8.0Hz, 1H), 4.97 (brs, 1H), 3.80-3.72 (m, 2H), 3.40-3.30 (m, 2H), 3.00-2.95 (m , 4H), 2.05-1.90 (m, 6H), 1.80-1.70 (m, 2H), 1.60-1.50 (m, 4H), 0.36-0.33 (m, 4H); LCMS m / z =539 (100%). Example 16: 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxo-1',2'- dihydrospiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridin]-5'-yl)-2-(6-azaspiro [2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.56 (s, 1H), 10.95 (s, 1H), 10.10 (s, 1H), 8.38- 8.34 (m, 1H), 8.10-8.02 (m, 1H), 7.84-7.76 (m 1H), 7.18-7.12 (m, 1H), 7.06-6.96 (m, 1H), 4.97 (brs, 1H), 3.80-3.70 (m, 2H), 3.65-3.55 (m, 2H), 3.00-2.90 (m , 4H), 2.10-1.85 (m, 4H), 1.80-1.70 (m, 4H), 1.60-1.50 (m, 4H), 0.25-0.15 (m, 4H); LCMS m / z = 540 (100%). Example 17: 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclohexane- 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.83 (s, 1H), 10.32 (s, 1H), 10.10 (s, 1H), 7.88- 7.84 (m, 2H), 7.78-7.74 (m, 1H), 7.19-7.16 (m, 1H), 6.80-6.40 (m, 1H), 4.97 (brs, 1H), 3.78-3.72 (m, 2H), 3.02-2.92 (m , 4H), 1.86-1.66 (m, 8H), 1.62-1.54 (m, 5H), 1.52-1.42 (m, 4H), 0.20-0.15 (m, 4H); LCMS m / z = 553 (100%). Example 18: 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 10.88 (s, 1H), 10.15 (s, 1H), 7.80-7.75 (m, 1H), 7.55-7.50 (m, 1H), 7.14-7.04 (m, 2H), 7.02-6.95 (m, 2H), 4.97 (brs, 1H), 3.80- 3.70 (m, 2H), 3.40-3.30 (m, 2H), 3.05-2.95 (m , 4H), 2.05-1.90 (m, 6H), 1.85-1.75 (m, 2H), 1.45-1.35 (m, 4H), 0.40-0.30 (m, 4H); LCMS m / z = 539 (100%). Example 19: 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclohexane- 1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 10.82 (s, 1H), 10.22 (s, 1H), 7.80-7.74 (m, 1H), 7.63-7.57 (m, 1H), 7.30-7.24 (m, 1H), 7.20-7.09 (m, 1H), 7.02-6.95 (m, 2H), 4.98 (brs, 1H), 3.76 (t, J=6.4Hz, 2H), 3.00-2.90 (m, 4H), 1.90-1.80 (m, 2H), 1.75-1.60 (m, 6H), 1.60-1.50 (m, 4H), 1.45-1.35 (m, 4H), 0.30-0.20 (m, 4H); LCMS m / z = 553 (100%). Example 20: 4-((2-Hydroxyethyl)sulfonamido)-N-(2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.57 (s, 1H), 10.42 (s, 1H), 10.10 (s, 1H), 7.99- 7.95 (m, 1H), 7.85-7.80 (m, 1H), 7.68-7.64 (m, 1H), 7.18-7.14 (m, 1H), 7.44-7.00 (m, 1H), 6.90-6.86 (m, 1H), 4.98 (brs, 1H), 4.10-4.00 (m, 2H), 3.90-3.80 (m, 2H), 3.80-3.70 (m, 2H), 3.65-3.55 (m, 2H), 3.00-2.90 (m, 4H), 1.90-1.80 (m, 2H), 1.80-1.75 (m, 2H), 1.65-1.50 (m, 4H), 0.40-0.30 (m, 4H); LCMS m / z = 555 (100%). Example 21: 4-((2-Hydroxyethyl)sulfonamido)-N-(1-methyl-2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.60 (s, 1H), 10.10 (s, 1H), 8.06-8.02 (m, 1H), 7.85-7.80 (m, 1H), 7.78-7.72 (m, 1H), 7.18-7.12 (m, 1H), 7.10-7.00 (m, 2H), 4.98 (brs, 1H), 4.10-4.00 (m, 2H), 3.90-3.80 (m, 2H), 3.80-3.70 (m, 2H), 3.50-3.40 (m, 1H), 3.20-3.10 (m, 4H), 3.05-2.95 (m, 4H), 1.90-1.80 (m, 2H), 1.70-1.50 (m, 6H), 0.40-0.30 (m, 4H); LCMS m / z = 569 (100%). Example 22: 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.69 (s, 1H), 10.08 (s, 1H), 7.83 (d, J= 8.4Hz, 1H), 7.77-7.73 (m, 1H), 7.68-7.62 (m, 1H), 7.57 (dd, J= 8.4Hz , 2Hz, 1H), 7.18- 7.15 (m, 1H), 7.05-6.95 (m, 2H), 4.97 (brs, 1H), 3.80-3.72 (m, 2H), 3.13 (s, 3H), 3.00-2.95 (m , 4H), 2.05-1.90 (m, 6H), 1.80-1.70 (m, 2H), 1.60-1.50 (m, 4H), 0.2- 0.15 (m, 4H); LCMS m / z = 553 (100%). Example 23: 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclohexane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.83 (s, 1H), 10.08 (s, 1H), 7.93-7.91 (m, 1H), 7.88-7.81 (m, 2H), 7.19-7.16 (m, 1H), 7.10-7.00 (m, 2H), 4.97 (brs, 1H), 3.80- 3.70 (m, 2H), 3.13 (s, 3H), 3.05-2.95 (m , 4H), 1.90-1.65 (m, 8H), 1.60-1.40 (m, 8H), 0.25-0.15 (m, 4H); LCMS m / z = 567 (100%). Example 24: 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.17 (s, 1H), 10.10 (s, 1H), 7.84-7.80 (m, 1H), 7.45-7.40 (m, 1H), 7.20-7.12 (m, 2H), 7.10-7.10 (m, 2H), 4.97 (brs, 1H), 3.80- 3.70 (m, 2H), 3.40-3.30 (m, 2H), 3.17 (s, 3H), 3.05-2.95 (m, 4H), 1.95-1.85 (m, 2H), 1.70-1.50 (m, 10H), 0.40-0.30 (m, 4H); LCMS m / z = 553 (100%). Example 25: 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclohexane-1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 11.17 (s, 1H), 10.10 (s, 1H), 7.84-7.80 (m, 1H), 7.44-7.40 (m, 1H), 7.20-7.18 (m, 1H), 7.16-7.12 (m, 1H), 7.10-7.00 (m, 2H), 4.98 (brs, 1H), 3.76 (t, J=6.4Hz, 2H), 3.17 (s, 3H), 3.05-2.95 (m, 4H), 1.95-1.85 (m, 2H), 1.70-1.50 (m, 14H), 0.40-0.30 (m, 4H); LCMS m / z = 567 (100%). Example 26: 5-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-3-(6-azaspiro[2.5]octan-6-yl)picolinamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 1 by using appropriate starting materials.1H NMR (400MHz, DMSO-d6) δ: 10.30 (s, 1H), 10.25 (s, 1H), 8.05-7.98 (m, 1H), 7.64-7.54 (m, 2H), 7.32-7.28 (m, 1H), 6.82-6.77 (m, 1H), 4.90 (brs, 1H), 3.76 (t, J=6.4Hz, 2H), 3.10-3.00 (m, 4H), 2.00-1.85 (m, 6H), 1.80-1.70 (m, 2H), 1.50-1.40 (m, 4H), 1.30-1.20 (m, 2H), 0.40-0.30 (m, 4H); LCMS m / z = 540 (100%). Example 27: 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6-yl)nicotinamide A mixture of 6-chloro-N-(2'-oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-4-(6- azaspiro[2.5]octan-6-yl)nicotinamide (50 mg, 0.111mmol), 2-hydroxyethane-l- sulfonamide (27.8mg, 0.222mmol) K3PO4(23.56mg, 0.333mmol), (1R,2R)- N1,N2-dimethylcyclohexane-1.2-diamine (15.78mg, 0.111mmol) and copper(I) iodide (190.45mg, 0.222mmol) in DMF (2mL) was heated at 90°C for 16h. Then the reaction mixture was filtered through a plug of celite and the filter cake was rinsed with 2 x 20ml of EtOAc. The filtrate was washed with water (20ml) followed by brine (20ml), dried over Na2SO4,filtered and concentrated. The concentrate was purified by reverse phase preparative HPLC to provide the title compound (7mg) as an off white solid. 1H NMR (400MHz, DMSO-d6) δ: 10.27 (s, 1H), 10.19 (s, 1H), 7.98-7.70 (m, 1H), 7.62-7.58 (m, 1H), 7.48-7.42 (m, 1H), 6.82-6.78 (m, 1H), 6.58-6.52 (m, 1H), 4.90 (brs, 1H), 3.76 (t, J=6.4Hz, 2H), 3.20- 3.10 (m, 4H), 2.00-1.85 (m, 6H), 1.80-1.70 (m, 2H), 1.45-1.35 (m, 4H), 1.30-1.20 (m, 2H), 0.40-0.30 (m, 4H); LCMS m / z = 540 (100%). Example 28: 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane- 1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)nicotinamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 27 by using appropriate starting materials. 1H NMR (400MHz, DMSO-d6) δ: 11.57 (s, 1H), 10.28 (s, 1H), 9.91 (s, 1H), 8.22- 8.16 (m, 1H), 7.53-7.49 (m, 1H), 6.82-6.78 (m, 1H), 6.68-6.58 (m, 1H), 4.98 (brs, 1H), 3.78-3.74 (m, 2H), 3.20-3.10 (m, 4H), 2.00-1.85 (m, 6H), 1.80-1.70 (m, 2H), 1.45-1.30 (m, 6H), 0.40-0.30 (m, 4H); LCMS m / z = 540 (100%). Example 29: 6-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6- yl)nicotinamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 27 by using appropriate starting materials. 1H NMR (400MHz, DMSO-d6) δ: 10.27 (s, 1H), 8.00-7.80 (m, 1H), 7.69-7.65 (m, 1H), 7.60-7.52 (m, 1H), 7.00-6.95 (m, 1H), 6.55-6.50 (m, 1H), 4.90 (brs, 1H), 3.76 (t, J=6.4Hz, 2H), 3.20-3.10 (m, 4H), 3.11 (s, 3H), 2.00-1.90 (m, 6H), 1.80- 1.70 (m, 2H), 1.45-1.35 (m, 6H), 0.35-0.25 (m, 4H); LCMS m / z = 554 (100%). Example 30: N-(4-((6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-yl)amino)-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-7-yl)-2- hydroxyethane-1-sulfonamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 27 by using N-(7-bromo-5-(6- azaspiro[2.5]octan-6-yl)quinazolin-4-yl)-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-amine as a starting material. 1H NMR (400MHz, DMSO-d6) δ: 12.40 (s, 1H), 10.30 (s, 1H), 8.60-8.40 (m, 1H), 7.35-7.25 (m, 3H), 7.22-7.18 (m, 1H), 6.75-6.70 (m, 1H), 4.95 (brs, 1H), 4.22- 4.15 (m, 1H), 3.93-3.87 (m, 1H), 3.80-3.70 (m, 4H), 3.40-3.30 (m, 1H), 3.30-3.16 (m, 2H), 3.00-2.90 (m, 1H), 2.90-2.80 (m, 2H), 2.30-2.15 (m, 2H), 1.85-1.75 (m, 2H), 1.70-1.40 (m, 3H), 1.25-1.00 (m, 4H), 0.5-0.35 (m, 4H); LCMS m / z = 283 (100%). Example 31: N-(4-((8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- d][1,4]oxazin-2-yl)amino)-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-7-yl)-2- hydroxyethane-1-sulfonamide The title compound was prepared by following same reaction protocol as described in the synthesis of example 27 by using N-(7-bromo-5-(6- azaspiro[2.5]octan-6-yl)quinazolin-4-yl)-8,8-difluoro-6,6a,7,8,9,10- hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-amine as a starting material. 1H NMR (400MHz, DMSO-d6) δ: 12.33 (s, 1H), 8.60-8.40 (m, 1H), 7.51-7.48 (m, 1H), 7.30-7.26 (m, 2H), 7.19-7.15 (m, 1H), 6.81-6.77 (m, 1H), 4.95 (brs, 1H), 4.32-4.25 (m, 1H), 4.04-3.93 (m, 2H), 3.80-3.75 (m, 2H), 3.40-3.30 (m, 2H), 3.25-3.15 (m, 2H), 2.95-2.75 (m, 3H), 2.30-2.10 (m, 5H), 1.90-1.70 (m, 2H), 1.10-1.00 (m, 2H), 0.5-0.35 (m, 4H); LCMS m / z = 601 (100%). Abbreviations °C = degree Celsius DMSO = Dimethyl sulphoxide DIPEA = Diisopropylethyl amine DMF = Dimethylformamide NMP = N-Methylpyrrolidone EtOAc = Ethyl acetate h = hour HATU = N-[(Dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]- N-methylmethanaminium hexafluorophosphate N-oxide 1H NMR = Proton nuclear magnetic resonance LCMS = Liquid chromatography-mass spectrometry m / z = mass to charge ratio mg = milligram ml = milliliter Na2SO4= Sodium sulphate K3PO4= Potassium phosphate LiOH = Lithium hydroxide NaOH = Sodium hydroxide PdCl2dppf.CH2Cl2= [1,1′Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane Pd2dba3= Tris(dibenzylideneacetone)dipalladium(0) T3P = Propanephosphonic acid anhydride THF = Tetrahydrofuran Xantphos = 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene PHARMACOLOGICAL ACTIVITY: KIF18A biochemical assay Inhibition of Microtubule stimulated ATPase activity of KIF18A by compounds was measured using ADP GLO assay (Promega (# V9102)). Compounds, enzyme, and ATP were diluted in reaction buffer containing 15 mM Tris, pH 7.5 (sigma), 10 mM MgCl2 (sigma), 0.01% Pluronic F-68 (Life Technologies Inc), 1 μM Taxol (Cytoskeleton Inc), and 30 μg / mL pig microtubules (Cytoskeleton Inc). Recombinant human KIF18A (1-467 His-tagged) protein was expressed using a E.Coli Rosetta system and purified by NI-NTA affinity chromatography. 4µL of compound, 2µL KIF18A protein and 2µL microtubules were added to reaction buffer and incubated for 10 minutes at room temperature. ATP (100 μM) was added to the reaction mixture to initiate the reaction and incubated for an additional 30 minutes at room temperature.5 µl of ADP GloTM reagent was then added and incubated further in the dark for 30 minutes. 10 µl of Kinase-Glo detection reagent was added to reaction mixture and incubated for 30 minutes at room temperature. Luminescence counts were measured on a Multimode plate reader (PerkinElmer). Calculation % Inhibition = 100- ((RLU in compound treated well-Blank) / (RLU in DMSO well-Blank)*100). Compound # % inhibition @ 100 nM 1 *** 2 ** 3 ** 4 * 5 * 6 ** 7 ** 8 ** 9 * 10 ** 11 *** 12 * 13 * 14 ** 15 *** 16 ** 17 *** 18 * 19 * 20 ** 21 ** 22 *** 23 *** 24 * 25 * 26 ** 27 ** 28 * 29 ** 30 * 31 * % inhibition @ 100 nM: > 70% = ***; 50% -70% = **; < 50% = *

Claims

We claim:

1. A compound of Formula (I)wherein, X1 , X2 , and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is select 8 1 ed from -NR - or -O-; L is select 8 8 8 8 2 ed from -NR SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, -2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano,substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, -2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof.

2. A compound of Formula (II)wherein, X1 , X2 , and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is selected fro 8 1 m -NR - or -O-; L is selected from -NR8SO -, -S 8 8 8 22O2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, -2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, -2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl;R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof.

3. A compound of formula (III)wherein, X1 , X2 , X3, X4 , X5, and X6 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is sele 8 1 cted from -NR - or -O-; L 8 8 8 8 2 is selected from -NR SO2-, -SO2NR -, -NR CO-, and -CONR -;two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, -2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, -2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl;R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof.

4. A compound of formula (IV)(IV) wherein, ring A is substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; X1 , X2 , X3, X4 , and X5 are each independently selected from N or CR5; L is selected fro 6 1 m -NR - or -O-; L is selected from -NR7SO -, -SO NR7-, -NR7CO-, a 7 22 2nd -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted-heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, -2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R5 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R6 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2 or 4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof.The compounds of formula (I), (II), (III) or (IV) as claimed in claim 1 to 4, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof, wherein the compounds are selected from the group comprising of: N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-yl)-4- 1 ((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide (S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- 2 yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- 3 yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(4-methyl-6,6a,7,8,9,10- 4 hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide N-(8,8-Difluoro-4-methyl-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- 5 d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide (S)-N-(6,6a,7,8,9,10-Hexahydrodipyrido[2,3-b:1',2'-d][1,4]oxazin-2- 6 yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide N-(8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- 7 d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide rel-(R)-N-(8,8-difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- 8 d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide rel-(S)-N-(8,8-difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- 9 d][1,4]oxazin-2-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6- azaspiro[2.5]octan-6-yl)benzamide N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-4-yl)-4- 10 ((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide (S)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-4- 11 yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide (R)-N-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-4- 12 yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamideN-(6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-3-yl)-4- ((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(6-oxo-6,6a,7,8,9,10-hexahydro- 5H-pyrido[1,2-a]quinoxalin-2-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane-1,3'- indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxo-1',2'- dihydrospiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridin]-5'-yl)-2-(6- azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclohexane-1,3'- indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane-1,3'- indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclohexane-1,3'- indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1-methyl-2-oxo-2',3',5',6'- tetrahydrospiro[indoline-3,4'-pyran]-5-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclohexane-1,3'-indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclopentane-1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 4-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2'- oxospiro[cyclohexane-1,3'-indolin]-7'-yl)-2-(6-azaspiro[2.5]octan-6- yl)benzamide 5-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane-1,3'- indolin]-5'-yl)-3-(6-azaspiro[2.5]octan-6-yl)picolinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane-1,3'- indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6-yl)nicotinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(2'-oxospiro[cyclopentane-1,3'- indolin]-5'-yl)-2-(6-azaspiro[2.5]octan-6-yl)nicotinamide 6-((2-Hydroxyethyl)sulfonamido)-N-(1'-methyl-2' oxospiro[cyclopentane-1,3'-indolin]-5'-yl)-4-(6-azaspiro[2.5]octan-6- yl)nicotinamideN-(4-((6,6a,7,8,9,10-Hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-2- 30 yl)amino)-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-7-yl)-2- hydroxyethane-1-sulfonamide N-(4-((8,8-Difluoro-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2- 31 d][1,4]oxazin-2-yl)amino)-5-(6-azaspiro[2.5]octan-6-yl)quinazolin-7- yl)-2-hydroxyethane-1-sulfonamide 6. A process for preparing heterocyclic compound of Formula (I)wherein, X1 , X2 and X3 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L is selected from - 8 1 NR - or -O-; L is selected from -NR8SO - 8 8 8 22, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, -2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicycliccarbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, -2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl; R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including isotopes thereof, comprising the step of: treating compound (23)wherein R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH- or with compound (6)wherein R2 is hydrogen, X1 and X2 are -CH- or with compound (12)wherein R2 is hydrogen, X1 and X2 are -CH-, Y is CH2- or -O-, n is 1 or 2 or with compound (14)wherein R2 is hydrogen, X1 and X2 are -CH-, Y is CH2- or -O-, n is 1 or 2 by using acid amine coupling reaction to give compounds of Formula (I).

7. A process for preparation of compound (4)wherein, R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH-, comprising the steps of: i) reacting compound (1);with heterocycles in presence of base in a solvent to obtain compound (2);wherein R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH-ii) treating the compound (2) of step i) in Buchwald–Hartwig amination reaction using a base and BINAP as ligand in presence of solvent and catalyst to obtain compound (3); andiii) reducing the compound (3) to obtain compound (4).

8. The process as claimed in claim 7, wherein the base in step (i) is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate magnesium carbonate or mixtures thereof.

9. The process as claimed in claim 8, wherein the base is caesium carbonate.

10. The process as claimed in claim 7, wherein the solvent in step (i) is selected from the group comprising acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, tetrahydrofuran, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof.

11. The process as claimed in claim 10, wherein the solvent is acetonitrile.

12. The process as claimed in claim 7, wherein the catalyst in step (ii) is selected from the group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II),Palladium(II) acetate, tetrakis (triphenylphosphine)palladium(0) and tris(dibenzylideneacetone) dipalladium(0).

13. The process as claimed in claim 12, wherein the catalyst is Tris(dibenzylideneacetone)dipalladium(0).

14. The process as claimed in claim 7, wherein the solvent in step (ii) is selected from a group comprising toluene, 1,2-dimethoxy ethane, diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, dioxane, methanol, DMSO, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof.

15. The process as claimed in claim 14, wherein the solvent is toluene.

16. The process as claimed in claim 7, wherein the base in step (ii) is selected from a group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, ammonium hydroxide, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride or mixtures thereof.

17. The process as claimed in claim 16, wherein the base is sodium tertiary butoxide.

18. A process for preparing compound (23)comprising the steps of: i) treating a compound (19)with heterocycles in presence of base and a solvent to obtain compound (20);wherein R3 is heterocycle, ii) treating the compound of formula (20) obtained in the step (i) with sulfonyl chloride in presence of a base and a solvent to obtain compound (21); andiii) hydrolysing the compound (21) to obtain compound (23).

19. The process as claimed in claim 18, wherein the base in step (i) is selected from a group comprising sodium carbonate, sodium tertiary butoxide, sodium hydride, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, lithium hydride, magnesium carbonate or mixtures thereof.

20. The process as claimed in claim 19, wherein the base is potassium carbonate.

21. The process as claimed in claim 18, wherein the solvent in step (i) is selected from the group comprising toluene, 1,2-dimethoxy ethane, tetrahydrofuran, diethylether, chlorinated solvent, acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, tetrahydrofuran, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof.

22. The process as claimed in claim 21, wherein the solvent is DMSO.

23. The process as claimed in claim 18, wherein the base in step (ii) is selected from a group comprising triethyl amine, sodium carbonate, sodium tertiary butoxide, sodium hydride, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, lithium hydride, magnesium carbonate or mixtures thereof.

24. The process as claimed in claim 23, wherein the base is triethyl amine.

25. The process as claimed in claim 18, wherein the solvent in step (ii) is selected from the group comprising toluene, 1,2-dimethoxy ethane, tetrahydrofuran, diethyl ether, chlorinated solvent, acetonitrile, malononitrile, propionitrile, ethanenitrile, benzonitrile, diethyl ether, dimethylformamide, dioxane, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof.

26. The process as claimed in claim 25, wherein the solvent is tetrahydrofuran.

27. A process for preparing heterocyclic compound of Formula (III)(III) wherein, X1 , X2 , X3, X4 , X5, and X6 are each independently selected from N or CR7; ring A is substituted- or unsubstituted- heterocycle; L 8 1 is selected from -NR - or -O-; L is selected f 8 8 8 8 2 rom -NR SO2-, -SO2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, -2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 , and R5 are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, -NR8C(=O)R8a, -OR8, -C(=O)OR8a, -2; R6 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl;R7 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R8 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R8a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2-4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes thereof, comprising the steps of: i) treating compound (25)wherein, R2 is hydrogen, R is hydrogen or fluorine, X1 and X2 are -CH- to obtain compound (26); andii) treating the compound (26) with sulfonamide in Buchwald condition followed by debenzylation to obtain the compounds of formula (III).

28. The process as claimed in claim 27, wherein the acid in step i) is selected from the group comprising acetic acid, formic acid, citric acid, phosphoric acid, oxalic acid, nitric acid.

29. The process as claimed in claim 28, wherein the acid is acetic acid.

30. The process as claimed in claim 27, wherein the sulfonamide in step ii) is selected from the group comprising sulfamethoxazole, sulfadoxine, sulfapyridine, sulfadiazine, 2-(benzyloxy) ethane-1-sulfonamide or mixtures thereof.

31. The process as claimed in claim 30, wherein the sulfonamide is 2-(benzyloxy) ethane-1-sulfonamide.

32. A process for preparing heterocyclic compound of Formula (IV)(IV) wherein, ring A is substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; X1 , X2 , X3, X4 , and X5 are each independently selected from N or CR5; L1is selected from -NR6- or -O-; L is selected from -NR7SO -, -SO 7 7 7 22 2NR -, -NR CO-, and -CONR -; two R1 together either from adjacent atoms or from same carbon will form a substituted- or unsubstituted- 4-8 membered heterocycle, substituted- or unsubstituted- 3-8 membered carbocycle; R2 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- five to six membered heteroaryl, -2; R3 is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to ten membered monocyclic or bicyclic heteroaryl, substituted- or unsubstituted four to twelve membered monocyclic or bicyclic carbocycle, and substituted- or unsubstituted four to twelve membered monocyclic or bicyclic heterocycle; R4 is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, and substituted- or unsubstituted- aryl, substituted- or unsubstituted- five to six membered heteroaryl;R5 is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle; R6 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7 is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; R7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl; n is an integer selected from 2 or 4; and or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs or deuterated compounds including their isotopes, combinations and use thereof and comprising the step of: reacting compound (24);wherein R2 is hydrogen, X1 and X2 is -CH-or with compound (16),wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, or with compound (18),wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, to obtain the compound of Formula (IV).

33. A process for preparing compound (10), comprising the steps of: i) treating compound (7)with heterocycles in presence of a suitable base to obtain compound (8)wherein R2 is hydrogen, X1 and X2 is -CH-; ii) treating compound (8) obtained in step i) in acidic condition to obtain compound (9); andiii) treating compound (9) with heterocycles in Buchwald condition using a base and BINAP as ligand in presence of a solvent and catalyst followed by reduction to obtain compound (10);wherein R2 is hydrogen, X1 and X2 is -CH-.

34. The process as claimed in claim 33, wherein the base in step i) is selected from the group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, or sodium t-butoxide.

35. The process as claimed in claim 34, wherein the base is caesium carbonate or sodium t-butoxide.

36. The process as claimed in claim 33, wherein the base in step iii) is selected from the group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride.

37. The process as claimed in claim 36, wherein the base is sodium t-butoxide.

38. The process as claimed in claim 33, wherein the solvent in step iii) is selected from the group comprising toluene, 1,2-dimethoxy ethane, diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, methanol, DMSO,dioxane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, diisopropyl ether or mixtures thereof.

39. The process as claimed in claim 38, wherein the solvent is toluene.

40. The process as claimed in claim 33, wherein the catalyst in step iii) is selected from the group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf .CH2Cl2), Palladium(II) acetate ([Pd(OAc)2]n), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) or tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3).

41. The process as claimed in claim 40, wherein the catalyst is Pd(OAc)2.

42. A process of preparing compound (16),wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, comprising the reduction of compound (15)wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, to obtain compound (16).

43. A process of preparing compound (18)wherein R is hydrogen, X1 and X2 is -CH-, n is 1 or 2, comprising the steps of: i) methylation of compound (15) in presence of a base;wherein R2 is hydrogen, X1 and X2 is -CH-, n is 1 or 2, to obtain compound (17)<img src='' class="img-anchor img-center" img-id="IMGF000144_0002" / >ii) reduction of compound (17) to obtain compound (18).

44. A pharmaceutical composition comprising a compound of formula (I) or (II) or (III) or (IV), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, and a pharmaceutically acceptable excipient or carrier.

45. Use of compound of formula (I) or (II) or (III) or (IV), or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereoffor manufacturing a medicament for a treatment of a cancer associated with KIF18A protein.

46. Use of compound of formula (I) or (II) or (III) or (IV), or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for a treatment of a cancer associated with KIF18A protein.

47. A method of treating cancer by administering to a subject therapeutically effective amount of a pharmaceutical composition comprising at least one or more of the compounds of formula (I) or (II) or (III) or (IV), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

48. The method as claimed in claim 47, wherein the subject has cancer.

49. The method as claimed in claim 48, wherein the cancer is associated with KIF18A protein.

50. The method as claimed in any one of claims 47 to 49, wherein the cancer is a solid tumor or hematopoietic tumor.

51. The method as claimed in claim 50, wherein the solid tumor is selected from breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, stomach cancer, rhabdomyosarcoma, fibrosarcoma, thyroid follicular cancer or Kaposi's sarcoma, melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoactanthoma or uterine cancer.

2. The method as claimed in claim 51, wherein the hematopoietic tumor is selected from the group comprising: (a) a hematopoietic tumor of lymphoid lineage selected from leukemia, acute lymphocitic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell-20 lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma or Burkett's lymphoma; and (b) a hematopoietic tumor of myeloid lineage selected from acute and chronic myelogenous leukaemia‟s, myelodysplastic syndrome or promyelocytic leukemia.

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