BICYCLIC COMPOUNDS AS INHIBITORS OF PD1/PD-L1 INTERACTION/ACTIVATION

Title:

BICYCLIC COMPOUNDS AS INHIBITORS OF PD1/PD-L1 INTERACTION/ACTIVATION

Document Type and Number:

WIPO Patent Application WO/2019/175897

Kind Code:

Abstract:

The compounds of Formula I is described herein along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof. The compounds described herein, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof are bicyclic compounds that are inhibitors of PD-1/PD-L1 interaction/activation.

Inventors:

VENKATESHAPPA CHANDREGOWDA (IN)
D A JEYARAJ (IN)
PENDYALA MURALIDHAR (IN)
SIVANANDHAN DHANALAKSHMI (IN)
RAJAGOPAL SRIDHARAN (IN)

Application Number:

PCT/IN2019/050203

Publication Date:

September 19, 2019

Filing Date:

March 13, 2019

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Assignee:

JUBILANT BIOSYS LTD (IN)

International Classes:

C07D401/14; A61P35/00; C07C217/58; C07C229/14; C07C229/48; C07C233/36; C07C255/54; C07D207/16; C07D209/54; C07D211/56; C07D211/60; C07D213/85; C07D221/04; C07D265/30; C07D401/12; C07D403/12; C07D405/12; C07D471/04; C07D491/107

Domestic Patent References:

WO2015034820A1	2015-03-12
WO2010048207A2	2010-04-29
WO2008051757A1	2008-05-02
WO2004052846A1	2004-06-24
WO2018026971A1	2018-02-08
WO2017106634A1	2017-06-22

Foreign References:

US20090069373A1	2009-03-12
EP3112362A1	2017-01-04
US9067898B1	2015-06-30
US20090264433A1	2009-10-22

Other References:

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY OR THE JOURNAL OF BIOLOGICAL CHEMISTRY

Attorney, Agent or Firm:

LAKSHMIKUMARAN, Malathi et al. (IN)

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Claims:

I/We Claim:

1. A compound of Formula I

Formula (I)

their polymorphs, stereoisomers, tautomer’s, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH2O-, -OCH2-, -C(0)NH- or -NHC(O)-;

R₄ is selected from hydrogen, hydroxyl, Ci_-6 alkyl, amino, -C(0)0R_ai, C(0)NR_biR_ci, C_5- ₆ aryl, or Ci_-6 heteroaryl, wherein Ci_-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NRbiRd, C5-6 aryl, and Ci_-6 heteroaryl;

R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

X is selected from CR3 or N;

R^a is selected from hydrogen, cyano, Ci_-6 alkyl, C_1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, Cw alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^CR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, C1-6 alkyl, C1-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the C1-6 alkyl, C1-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl- C1-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents; R^f is selected from Ci alkyl, Ci-₄ haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the Ci_₄ alkyl, C 1-4 haloalkyl, C₂-6 alkenyl, C₂-6 alkynyl, C6-ioaryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

R^g is selected from hydrogen, Ci_-6 alkyl, C 1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

Rⁿ is selected from cyano, halo, C_1-4 alkyl, C_3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-₄ alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-6 membered heteroaryl)-Ci-₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci-₄ alkyl-, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C _1-4 haloalkyl, R°, NHOR⁰, OR⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

NR⁰C(=NR°)NR°R⁰, S(0)R°, S(0)NR°R°, S(0)₂R°, NR°S(0)₂R°, NR°S(0)₂NR°R⁰, or S(0)₂NR°R°, wherein the C ₁ alkyl, C_3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6- 10 aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl and C_1-4 haloalkyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^p is selected from halo, cyano, Ci_-6 alkyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)0R^r, 0C(0)R^r, 0C(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)0R^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=NCN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, Ci_-6 alkyl, Ci_-6 alkoxy, Ci_-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C 1-4 haloalkoxy, wherein the Ci_-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C 1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci-₆ alkyl;

m is 1 or 2;

Ring A is selected from substituted or unsubstituted C5-10 aryl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O;

Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic, saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

2. A compound of Formula II

Formula II

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH₂0-, -OCH2-, -C(0)NH- or -NHC(O)-;

R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

R₅ is selected from C_1-4 alkyl, cyano, or C_1-4 haloalkyl;

Ri, R₂, R₃, R₆, and R₇ are independently selected from hydrogen, halo, Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, CN, N0₂, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC (=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^a is selected from hydrogen, cyano, Ci_-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^c is selected from hydrogen, C_1-6 alkyl, C_1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent; R^f is selected from Ci alkyl, Ci-₄ haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the Ci_₄ alkyl, C 1-4 haloalkyl, C₂-6 alkenyl, C₂-6 alkynyl, C6-ioaryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

R^p is selected from halo, cyano, Ci_-6 alkyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)0R^r, 0C(0)R^r, 0C(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)0R^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=NCN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the C_1-6 alkyl, C_1-6 haloalkyl, C_1-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R^q is selected from hydroxy, cyano, amino, halo, COOH, C _1-6 haloalkyl, C_1-6 alkyl, C_1-6 alkoxy, C_1-6 alkylthio, C_5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C_3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C _1-4 haloalkoxy, wherein the C_1-6 alkyl, C_5-6 aryl, C_3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_1-4 haloalkoxy, C_5-6 aryl, C_3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is C_1-6 alkyl;

Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O. 3. A compound of Formula III

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH₂0-, -OCH2-, -C(0)NH- or -NHC(O)-; R₄ is selected from hydrogen, hydroxyl, Ci_-6 alkyl, amino, -C(0)OR_ai, C(0)NR_biR_ci, C_5- ₆ aryl, or Ci_-6 heteroaryl; wherein Ci_-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)OR_ai, C(0)NRbiRd, C5-6 aryl, and Ci_-6 heteroaryl;

R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

R₅ is selected from C_1-4 alkyl, cyano, or C_1-4 haloalkyl;

Ri, R₂, R₃,R₆, and R₇ are independently selected from hydrogen, halo, Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C_3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, CN, N0₂, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)OR^a, OC(0)R^a, OC(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)OR^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC (=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^a is selected from hydrogen, cyano, Ci_-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3-10 cycloalkyl-Ci-4alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, C14 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^CR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, Ci-₄ haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl- C1-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^c is selected from hydrogen, Ci_-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent;

R^g is selected from hydrogen, C1-6 alkyl, C _1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

R^p is selected from halo, cyano, C_1-6 alkyl, C_1-6 haloalkyl, C_1-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, OC(0)R^r, OC(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)OR^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=NCN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the C_1-6 alkyl, C_1-6 haloalkyl, C _1-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C2-4 alkenyl, or C2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents;

R⁸ is Ci-₆ alkyl.

4. A compound of Formula IV

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

whereinR5 is selected from C1 alkyl, cyano, or C1-4 haloalkyl;

Ri, R₂, R₃,R₆, and R₇ are independently selected from hydrogen, halo, Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, CN, N0₂, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC (=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents; R^a is selected from hydrogen, cyano, Ci_-6 alkyl, Ci-₄ haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, C₁₄ alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^CR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^c is selected from hydrogen, Ci_-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the Ci_-6 alkyl, C_2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent;

R^f is selected from C alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the Ci_₄ alkyl, C 1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C6-ioaryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

R^g is selected from hydrogen, Ci_-6 alkyl, C 1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

R^p is selected from halo, cyano, Ci_-6 alkyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, OC(0)R^r, OC(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)OR^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=NCN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C 1-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C₂-4 alkenyl, or C_2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C₂-4 alkenyl, and C₂-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents;

R⁸ is Ci-₆ alkyl.

5. A compound of Formula V

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Rs is selected from CM alkyl, cyano, or Ci-₄ haloalkyl;

R₄ is selected from hydrogen, hydroxyl, Ci_-6 alkyl, amino, -C(0)0R_ai, C(0)NRbiRci, C_5- ₆ aryl, or Ci_-6 heteroaryl; wherein Ci_-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NRbiRci, C5-6 aryl, and Ci_-6 heteroaryl;

R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

R^a is selected from hydrogen, cyano, Ci_-6 alkyl, Ci-₄ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- , or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, C IM alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-₄ haloalkyl, Ci-₄ haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^CR^c; wherein the Ci-₄ alkyl, C_2-4 alkenyl, C_2-4 alkynyl, Ci-₄ haloalkyl, Ci-₄ haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^f is selected from C alkyl, Ci-₄ haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, (4-10 membered heterocyclo alkyl) -Ci-₄ alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the Ci_₄ alkyl, Ci-₄ haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, and (4-10 membered heterocycloalkyl)- Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

Rⁿ is selected from cyano, halo, Ci-₄ alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci-₄ alkyl-, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ci-₄ haloalkyl, R°, NHOR⁰, OR⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

R^g is selected from hydrogen, C1-6 alkyl, Ci-₄ haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-C i-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

R^p is selected from halo, cyano, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, OC(0)R^r, OC(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)OR^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=NCN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the C1-6 alkyl, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2 or 3 R^q substituents; R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, Ci-₄ alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C_IM haloalkyl, C2-4 alkenyl, or C2-4 alkynyl, wherein the Ci-₄ alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^q is selected from hydroxy, cyano, amino, halo, COOH, C _1-6 haloalkyl, Ci_-6 alkyl, Ci_-6 alkoxy, Ci_-6 alkylthio, C_5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C_3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and Ci-₄ haloalkoxy, wherein the Ci_-6 alkyl, C_5-6 aryl, C_3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C_IM alkyl, Ci-₄ alkoxy, Ci-₄ haloalkyl, Ci-₄ haloalkoxy, C_5-6 aryl, C_3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci-₆ alkyl.

6. A compound of Formula VI

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Rs is selected from C_M alkyl, cyano, or Ci-₄ haloalkyl;

R₄ is selected from hydrogen, hydroxyl, Ci_-6 alkyl, amino, -C(0)0R_ai, C(0)NR_biR_ci, C_5- ₆ aryl, or Ci_-6 heteroaryl; wherein Ci_-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NRbiRci, C5-6 aryl, and Ci_-6 heteroaryl;

R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

Ri, R₂, R₃,R₆, and R₇ are independently selected from hydrogen, halo, Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-14 membered heteroaryl)-Ci-₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, CN, N0₂, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)OR^a, OC(0)R^a, OC(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)OR^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC (=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, C₁ alkyl, C₂-4 alkenyl, C₂-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^CR^c; wherein the C1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl- C1-4 alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^p is selected from halo, cyano, Ci_-6 alkyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, OC(0)R^r, OC(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)OR^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=NCN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C _1-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R⁸ is Ci-₆ alkyl.

7. The compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or its polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, as claimed in any of the claims 1-6, is selected from a group consisting of:

(S)-l-((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl) piperidine-2-carboxylic acid (1),

N-(2-(((5-methoxy-7 -((2-methyl- [1,1 '-biphenyl] -3 -yl)methoxy) -2,3 -dihydro- lH-inden- 4-yl) methyl)amino)ethyl)acetamide (2),

(S)- l-((7-((3-(l-(3-(3 ,3 -difluoropyrrolidin- 1 -yl)propyl)- 1 H-indol-4-yl)-2- methylbenzyl)oxy)-2,3-dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (3), (S)- 1 -((6-methyl-7-((2-methyl- [1,1 '-biphenyl] -3-yl)methoxy)-2,3-dihydro- 1 H-inden-4- yl)methyl)piperidine-2-carboxylic acid (4),

(S)- 1 -((6-chloro-7-((2-methyl-[ 1 , 1 '-biphenyl] -3-yl)methoxy)-2,3-dihydro- 1 H-inden-4- yl)methyl)piperidine-2-carboxylic acid (5),

Methyl 7-(((2-acetamidoethyl)amino)methyl)-4-((2-methyl-[l,l'-biphenyl]-3- yl)methoxy)-2, 3-dihydro- lH-indene-5-carboxylate (6),

(S)-l-((7-((3'-(3-(3,3-difluoropyrrolidin-l-yl)propoxy)-2,2'-dimethyl-[l,l'-biphenyl]-3- yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (7),

(S)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (8),

(S)- l-((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[ 1,1 '-biphenyl] -3-yl)methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (9)

N-(2-(((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (10)

(S)-5-((5-methoxy-7-((2-methyl-[ l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden- 4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (11)

(S)-l-((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-5-(2,2,2-trifluoroethoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (12)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro- 1 H-inden-4-yl)methyl)amino)ethyl)-N-methylacetamide( 13)

N-(2-(((5-(l-(3-cyanophenyl)ethoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)amino)ethyl)acetamide (14) N-(l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidin-3-yl)acetamide (15)

N-(2-(((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl) amino)ethyl)acetamide (16)

6-((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)-2- oxa-6-azaspiro[3.3]heptane (17)

2-(hydroxymethyl)-2-(((7 -((2-methyl- [1,1 '-biphenyl] -3-yl)methoxy)-2,3-dihydro- 1 H- inden-4-yl)methyl)amino)propane- 1 ,3-diol (18)

1 -(((7-((2-methyl- [1,1 '-biphenyl] -3 -yl)methoxy)-2 ,3 -dihydro- 1 H-inden-4- yl)methyl)amino)cyclopropane-l -carboxylic acid (19)

((7-((2-methyl-[ l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)glycine (20)

3 -(((7-((2-methyl- [1,1 '-biphenyl] -3 -yl)methoxy)-2 ,3 -dihydro- 1 H-inden-4- yl)methyl)amino)propanoic acid (21)

N -methyl-N-((7 -((2-methyl- [1,1 '-biphenyl] -3 -yl)methoxy)-2, 3 -dihydro- 1 H-inden-4- yl)methyl)glycine (22)

3 -(((7-((2-methyl- [1,1 '-biphenyl] -3 -yl)methoxy)-2 ,3 -dihydro- 1 H-inden-4- yl)methyl)amino)butanoic acid (23)

((7-((2-methyl-[ l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl) alanine (24)

(2S ,4R)-4-hydroxy- 1 -((5-methoxy-7 -((2-methyl- [1,1 '-biphenyl] -3-yl)methoxy)-2, 3- dihydro-lH-inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (25)

(S)-l-((5-methoxy-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden- 4-yl)methyl)piperidine-2-carboxylic acid (26)

l-((4-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-5,6,7,8-tetrahydronaphthalen-l- yl)methyl)piperidine-2-carboxylic acid (27)

N-(2-(((6-methyl-7-((2-methyl-[ l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)ethyl)acetamide (28)

(2S,4R)-4-hydroxy-l-((6-methyl-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (29)

N-(2-(((6-chloro-7-((2-methyl- [1,1 '-biphenyl] -3-yl)methoxy)-2,3-dihydro- 1 H-inden-4- yl)methyl)amino)ethyl)acetamide (30)

(2S,4R)-l-((6-chloro-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (31) N-(2-(((7-((3 '-(3-(3 ,3 -difluoropyrrolidin- 1 -yl)propoxy)-2,2'-dimethyl- [1,1 '-biphenyl] -3- yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (32) (2S,4R)-l-((7-((3'-(3-(3,3-difluoropyrrolidin-l-yl)propoxy)-2,2'-dimethyl-[l,r- biphenyl] -3 -yl)methoxy) -5-methoxy-2,3 -dihydro- 1 H-inden-4-yl)methyl) -4- hydroxypyrrolidine-2-carboxylic acid (33)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)amino)ethyl)acetamide (34)

(2S,4R)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (35)

(S)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (36)

(S)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxamide (37)

3-(((4-(((l,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-7-((2-methyl- [l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-5-yl)oxy)methyl)benzonitrile (38) 3-(((4-((2-oxa-6-azaspiro [3.3]heptan-6-yl)methyl)-7 -((2-methyl- [1,1 '-biphenyl] -3- yl)methoxy)-2, 3-dihydro- lH-inden-5-yl)oxy)methyl)benzonitrile (39)

3-(((4-((3-hydroxypiperidin-l-yl)methyl)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-5-yl)oxy)methyl)benzonitrile (40)

((5-((3 -cyanobenzyl)oxy) -7-((2-methyl- [1,1 '-biphenyl] -3 -yl)methoxy)-2, 3 -dihydro- 1 H- inden-4-yl)methyl)glycine (41)

(S)-5-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (42) rac-(lR,6S)-2-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)-2-azabicyclo[4.l.0]heptane-l-carboxylic acid (cis, racemic) (43)

4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)amino)butanoic acid (44)

(lR,6S)-2-((5-methoxy-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-2,3-dihydro-lH- inden-4-yl) methyl)-2-azabicyclo [4. l.0]heptane-l-carboxylic acid (cis, racemic) (45) (S)-l-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (46) (2S,4R)-l-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (47)

N-(2-(((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-

2, 3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (48)

5-(((4-(((l,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-7-((2-methyl- [l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-5-yl)oxy)methyl)nicotinonitrile (49)

(S)-4-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-

2, 3-dihydro- lH-inden-4-yl)methyl)morpholine-3-carboxylic acid (50)

rac-(lR,6S)-2-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)-2-azabicyclo[4.1.0]heptane- 1- carboxylic acid (cis, racemic) (51)

(S)-5-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-

2, 3-dihydro- lH-inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (52) N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)(methyl)amino)ethyl)acetamide (53)

N-(2-(((5-((4-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)amino)ethyl)acetamide (54)

(S)-l-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)piperidine-2-carboxylic acid (55)

N-(2-(((7-((2-cyano-[ l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)amino)ethyl)acetamide (56)

(2S,4R)-l-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-lH- inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (57)

3-(((7-(((l,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-6-methoxy-2,3- dihydro- 1 H-inden-4-yl)oxy)methyl)- [ 1 , 1 '-biphenyl] -2-carbonitrile (58)

(S)-4-((7-((2-cyano-[ l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)morpholine-3-carboxylic acid (59)

((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)glycine (60)

(S)-5-((7-((2-cyano-[ l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (61) rac-(lR,6S)-2-((7-((2-cyano-[l,r-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- 1H- inden-4-yl)methyl)-2-azabicyclo[4.l.0]heptane-l-carboxylic acid (cis, racemic) (62) 2-(l-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)piperidin-2-yl)acetic acid (63)

N-(2-(((7-((2-cyano-[ l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)(methyl)amino)ethyl)-N-methylacetamide (64)

5-((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-5-yl)oxy)pentanoic acid (65)

5-((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-5-yl)oxy)pentanamide (66)

(S)-l-((5-(4-carboxybutoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (67)

(S)-l-((5-((5-amino-5-oxopentyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (68)

(S)-l-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-

2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (69)

(2S,4R)-l-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (70)

(R)-l-((7-((2-cyano-[l,r-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3-yl)methoxy)-

2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-3-carboxylic acid (71)

rac-(lR,6S)-2-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)-2-azabicyclo[4.1.0]heptane- 1- carboxylic acid (cis racemic) (72)

Methyl 4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro- 1 H-inden-4-yl)methyl)amino)bicyclo [2.2.2] octane- 1 -carboxylate (73 )

4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3-dihydro- 1 H-inden-4-yl)methyl)amino)bicyclo [2.2.2] octane- 1 -carboxylic acid (74)

(S)-l-((5-methoxy-7-((2-(trifluoromethyl)-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (75)

(2S,4R)-4-hydroxy-l-((5-methoxy-7-((2-(trifluoromethyl)-[l,r-biphenyl]-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (76) (2S)-l-((7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-5-((l-methylpiperidin-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (77) (S)-l-((5-(4-carboxybutoxy)-7-((2-cyano-[l,r-biphenyl]-3-yl)methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (78)

N-(2-(((5-(4-cyanobutoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (79)

(S)-l-((5-(4-cyanobutoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)piperidine-2-carboxamide (80)

(2S,4R)-l-((5-(4-cyanobutoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (81)

(S)-l-((5-(((lS,2R)-2-carboxycyclopropyl)methoxy)-7-((2-methyl-[l,l'-biphenyl]-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (82) (lR,2S)-2-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3- yl)methoxy)-2, 3-dihydro- lH-inden-5-yl)oxy)methyl)cyclopropane- l-carboxylic acid (83)

(S)-l-((7-((3-(2,3-dihydrobenzo[b][l,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methoxy-

2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (84)

(2S,4R)-l-((7-((3-(2,3-dihydrobenzo[b][l,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5- methoxy-2,3-dihydro-lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (85)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2,2'-dimethyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)amino)ethyl)acetamide (86)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((4'-fluoro-2-methyl-[ 1 , 1 '-biphenyl] -3-yl)methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (87)

(S)-l-((5-((3-carbamoylbenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (88)

3-(((4-(aminomethyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3-dihydro-lH- inden-5-yl)oxy)methyl)benzonitrile (89)

N-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)acetamide (90)

6-acetamido-N-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)hexanamide (91)

3-(((4-((dimethylamino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-5-yl)oxy)methyl)benzonitrile (92)

5-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-5-yl)oxy)methyl)nicotinic acid (93) 5-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)- 2, 3-dihydro- lH-inden-5-yl)oxy)methyl)nicotinamide (94)

3-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl] -3-yl)methoxy)- 2, 3-dihydro- lH-inden-5-yl)oxy)methyl)benzamide (95)

(S)-l-((3-methoxy-l-((2-methyl-[l,F-biphenyl]-3-yl)methoxy)-6,7-dihydro-5H- cyclopenta[c]pyridin-4-yl)methyl)piperidine-2-carboxylic acid (96)

N-(2-(((3-methoxy-l-((2-methyl-[l,F-biphenyl]-3-yl)methoxy)-6,7-dihydro-5H- cyclopenta[c]pyridin-4-yl)methyl)amino)ethyl)acetamide (97)

(S)-4-((5-methoxy-7-((2-methyl-[ l,F-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-

4-yl)methyl)morpholine-3-carboxylic acid (98)

5-((5-((3 -cyanobenzyl)oxy) -7 -((2-methyl- [1,1’-biphenyl] -3 -yl)methoxy)-2,3 -dihydro- lH-inden-4-yl)methyl)-4,5,6,7-tetrahydro-lH-pyrazolo[4,3-c]pyridine-3-carboxylic acid (99)

8. A process of preparation of compounds of Formula I, as claimed in claim 1 or its polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof.

9. The process of preparation of compounds of Formula I as claimed in claim 8, comprising: (a) reacting compounds of Formula I (a) with substituted aliphatic, aromatic, heterocyclic and cyclic amines to obtain compounds of Formula I

wherein the Xi of Formula I (a) and Formula I is selected from -CH₂0-, -OCFh-, - C(0)NH- or -NHC(O)-; R₄ of Formula I (a) and Formula I is selected from hydrogen, hydroxyl, Ci-6 alkyl, amino, -C(0)0R_ai, C(0)NRbiRd, C5-6 aryl, or C1-6 heteroaryl, wherein C_1-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NR_biR_ci, C_5-6 aryl, and C_1-6 heteroaryl; R_al, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;X of Formula I (a) and Formula I is selected from CR₃ or N; Ri, R₂, R₆, and R₇ of Formula I (a) and Formula I are independently selected from hydrogen, halo, Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5- 14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, CN, N0₂, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC (=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents; R^a is selected from hydrogen, cyano, C1-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6- 10 aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C1-6 alkyl, C_2-6 alkenyl, C_2- ₆ alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-4alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;R^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C₂-4 alkenyl, C₂-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^CR^c; wherein the C1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents ;R^C is selected from hydrogen, C1-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent; R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C_3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C_3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-C _1-4 alkyl-, C_3-10 cycloalkyl- C_1-4 alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^f is selected from C alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the Ci_₄ alkyl, C 1-4 haloalkyl, C₂-6 alkenyl, C₂-6 alkynyl, C_6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents; R^g is selected from hydrogen, Ci_-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^p substituents; Rⁿ is selected from cyano, halo, C1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci_-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, R°, NHOR⁰, OR⁰, SR°, C(0)R°, C(0)NR°R°, C(0)0R°, 0C(0)R°, 0C(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)0R°, C(=NR)NR°R°,

NR⁰C(=NR°)NR°R⁰, S(0)R°, S(0)NR°R°, S(0)₂R°, NR°S(0)₂R°, NR⁰S(0)₂NR°R⁰, or S(0)₂NR°R°, wherein the C 1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6- 10 aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci_-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl and C1-4 haloalkyl are optionally substituted with 1, 2 or 3 R^q substituents; R^p is selected from halo, cyano, C 1-6 alkyl, C 1-6 haloalkyl, Ci_-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, OC(0)R^r, OC(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)OR^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=NCN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents; R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C2-4 alkenyl, or C2- 4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents; R^q is selected from hydroxy, cyano, amino, halo, COOH, Ci-₆ haloalkyl, Ci_-6 alkyl, Ci-₆ alkoxy, Ci_-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl,

4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C haloalkoxy, wherein the Ci_-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, Ci-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R⁸ is Ci_-6 alkyl; m is 1 or 2; Ring A is selected from substituted or unsubstituted C5-10 aryl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O; Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O, with substituted amines in the presence of solvents to obtain compounds of Formula I.

10. A pharmaceutical composition comprising a compound of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or a pharmaceutically acceptable salt thereof as claimed in any of the claims 1-7, together with a pharmaceutically acceptable carrier, optionally in combination with one or more other pharmaceutical compositions.

11. The pharmaceutical composition as claimed in claim 10, wherein the composition is in the form selected from the group consisting of a tablet, capsule, powder, syrup, solution, aerosol and suspension.

12. A method for the treatment and/or prevention of various diseases, including cancer and infectious diseases, comprising administering to a subject suffering from the proliferative disorder or cancer a therapeutically effective amount of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI as claimed in any one of claims 1 - 7 or the pharmaceutical composition as claimed in claim 10, or 11, with other clinically relevant cytotoxic agents or non-cytotoxic agents to a subject in need thereof.

13. Use of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI as claimed in any one of claims 1 - 7, or the pharmaceutical composition as claimed in claim 10 or 11, for the treatment and/or prevention of various diseases including proliferative disorder or cancer; or treatment of cancer together with other clinically relevant cytotoxic agents or non-cytotoxic agents.

16. A method of treatment of cancer, said method comprising administering a combination of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI as claimed in any of claims 1 - 7, or the pharmaceutical composition as claimed in claim 10 or 11, with other clinically relevant immune modulators agents to a subject in need of thereof.

AMENDED CLAIMS

received by the International Bureau on 22 July 2019 (22.07.2019)

I/We Claim:

1. A compound of Formula I

Formula (I)

their polymorphs, stereoisomers, tautomer’s, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH2O-, -OCH2-, -C(0)NH- or -NHC(O)-;

R4 is selected from hydrogen, Ci-₆ alkyl, -C(0)0R_ai, C(0)NR_biRci, C5-6 aryl, or Ci-6 heteroaryl, wherein Ci-₆ alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NR_biR_d, C5-6 aryl, and Ci-₆ heteroaryl; R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci-₆ alkyl;

X is selected from CR3 or N;

Ri, R2, R3, R₆, and R7 are independently selected from hydrogen, halo, Ci-₆ alkyl, C2-6 alkenyl, C2- ₆ alkynyl, Ci-₆ haloalkyl, Ci-₆ haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO2, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)OR^a, OC(0)R^a, OC(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)OR^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC(=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5- 14 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^a is selected from hydrogen, cyano, Ci-₆ alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci- 4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3- io cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)- Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^cR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl) -C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, Ci-₆ alkyl, Ci-₆ haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- C1-4 alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci-₆ alkyl, Ci-₆ haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents; R^f is selected from Ci_-4 alkyl, Ci_-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- Ci-₄ alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)0R^g, 0C(0)R^g, 0C(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)0R^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

R^g is selected from hydrogen, Ci_-6 alkyl, C_1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- ₁₀ cycloalkyl -Ci -₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- _l0 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

S(0)₂NR°R°, wherein the C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl and C1-4 haloalkyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^P is selected from halo, cyano, C_l-6 alkyl, C_l-6 haloalkyl, C_l-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, 0C(0)R^r, 0C(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)0R^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=N CN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-io cycloalkyl-Ci_-4 alkyl-, (5- 10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1 , 2 or 3 R^q substituents;

R^q is selected from hydroxy, cyano, amino, halo, COOH, Ci_-6 haloalkyl, Ci_-6 alkyl, Ci-₆ alkoxy, Ci- ₆ alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C1-4 haloalkoxy, wherein the Ci_-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci -₆ alkyl;

m is 1 or 2;

Ring A is selected from substituted or unsubstituted C5-10 aryl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted 6-10 membered monocyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O;

Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

2. A compound of Formula II

Formula II

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH2O-, -OCH2-, -C(0)NH- or -NHC(O)-;

R4 is selected from hydrogen, Ci-₆ alkyl, -C(0)0R_ai, C(0)NRbiR_ci, C5-6 aryl, or Ci-₆ heteroaryl, wherein Ci-₆ alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NR_biR_ci, C5-6 aryl, and Ci-₆ heteroaryl; R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci-₆ alkyl;

R₅ is selected from C1-4 alkyl, cyano, or C1-4 haloalkyl;

Ri, R2, R3, Re, and R₇ are independently selected from hydrogen, halo, Ci-₆ alkyl, C2-6 alkenyl, C2- ₆ alkynyl, Ci-₆ haloalkyl, Ci-₆ haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO2, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC(=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5- 14 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^a is selected from hydrogen, cyano, Ci-₆ alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci- 4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- io cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^c is selected from hydrogen, Ci-₆ alkyl, C_1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- ₁₀ cycloalkyl -Ci -4 alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci-₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- ₁₀ cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent; R^f is selected from Ci_-4 alkyl, Ci_-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- Ci-₄ alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)0R^g, 0C(0)R^g, 0C(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)0R^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

Rⁿ is selected from cyano, halo, C1-4 alkyl, C3- 10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, CM haloalkyl, R°, NHOR⁰, OR⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR⁰C(=NR°)NR°R⁰, S(0)R°, S(0)NR°R°, S(0)₂R°, NR°S(0)₂R°, NR⁰S(0)₂NR⁰R°, or S(0)₂NR°R°, wherein the C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl and C1-4 haloalkyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^g is selected from hydrogen, Ci_-6 alkyl, C_1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- ₁₀ cycloalkyl -Ci -4 alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C_l-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- _l0 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

R^p is selected from halo, cyano, C_l-6 alkyl, C_l-6 haloalkyl, C_l-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, 0C(0)R^r, 0C(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)0R^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=N CN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_{3 i}o cycloalkyl-Ci-₄ alkyl-, (5- 10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C_1-4 alkyl, C_3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C_1-4 haloalkyl, C_2-4 alkenyl, or C_2-4 alkynyl, wherein the C_1-4 alkyl, C_3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C_2-4 alkenyl, and C_2-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^qis selected from hydroxy, cyano, amino, halo, COOH, Ci_-6 haloalkyl, Ci_-6 alkyl, Ci-₆ alkoxy, Ci- ₆ alkylthio, C_5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C_3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C_1-4 haloalkoxy, wherein the Ci_-6 alkyl, C_5-6 aryl, C_3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C_1-4 alkyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_1-4 haloalkoxy, C_5-6 aryl, C_3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci -₆ alkyl;

Ring B is selected from C_5-10 aryl, C_3-6 cycloalkyl, 5-10 membered monocyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

3. A compound of Formula III

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH2O-, -OCH2-, -C(0)NH- or -NHC(O)-; R4 is selected from hydrogen, Ci_-6 alkyl, -C(0)0R_ai, C(0)NRbiR_ci, C5-6 aryl, or Ci_-6 heteroaryl; wherein Ci_-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NR_biR_ci, C5-6 aryl, and Ci_-6 heteroaryl; R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

R₅ is selected from Ci_-4 alkyl, cyano, or C1-4 haloalkyl;

Ri, R₂, R₃,R₆, and R₇ are independently selected from hydrogen, halo, Ci_-6 alkyl, C2-6 alkenyl, C_2- ₆ alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO2, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC(=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5- 14 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^a is selected from hydrogen, cyano, Ci_-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci- 4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C_3- 10 cycloalkyl-Ci-4alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)- Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^cR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-₄ haloalkyl, Ci_-4 haloalkoxy, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl) -C _1-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- C1-4 alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)0R^e, 0C(0)R^e, 0C(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)0R^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^c is selected from hydrogen, Ci_-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl -Ci -₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C_l-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- _l0 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent;

R^f is selected from Ci-4 alkyl, Ci-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- C1-4 alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or

S(0)₂NR^gR^g; wherein the C1-4 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- _l0 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents; Rⁿ is selected from cyano, halo, Ci_-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ci-₄ haloalkyl, R°, NHOR⁰, OR⁰, SR°, C(0)R°, C(0)NR°R°, C(0)0R°, 0C(0)R°, 0C(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)0R°, C(=NR)NR°R°, NR⁰C(=NR°)NR°R⁰, S(0)R°, S(0)NR°R°, S(0)₂R°, NR°S(0)₂R°, NR⁰S(0)₂NR⁰R°, or S(0)₂NR°R°, wherein the C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl and C1-4 haloalkyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^g is selected from hydrogen, Ci-₆ alkyl, C_1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- ₁₀ cycloalkyl -Ci -₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci-₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- _l0 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

R^p is selected from halo, cyano, Ci-₆ alkyl, Ci-₆ haloalkyl, Ci-₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, OC(0)R^r, OC(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)OR^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=N CN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, Ci-₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_{3 i}o cycloalkyl-Ci-₄ alkyl-, (5- 10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C_1-4 alkyl, C_3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C_1-4 haloalkyl, C_2-4 alkenyl, or C2-4 alkynyl, wherein the Ci-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1 , 2 or 3 R^q substituents;

R^q is selected from hydroxy, cyano, amino, halo, COOH, Ci-₆ haloalkyl, Ci-₆ alkyl, Ci-₆ alkoxy, Ci- ₆ alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C1-4 haloalkoxy, wherein the Ci-₆ alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci -₆ alkyl.

4. A compound of Formula IV

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

whereinR₅ is selected from C1-4 alkyl, cyano, or C1-4 haloalkyl;

Ri, R₂, R3,R6, and R₇ are independently selected from hydrogen, halo, Ci-₆ alkyl, C2-6 alkenyl, C2- ₆ alkynyl, Ci-₆ haloalkyl, Ci-₆ haloalkoxy, C₆-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C₆-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO2, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC(=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C₆-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C₆-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5- 14 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1 , 2, 3, or 4 R^b substituents; R^a is selected from hydrogen, cyano, Ci_-6 alkyl, C_1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci- ₄ alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- ₁₀ cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)- Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^cR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-₄ haloalkyl, C_1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl) -C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- Ci-₄ alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^f is selected from Ci_-4 alkyl, Ci_-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C_3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- Ci-4 alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)0R^g, 0C(0)R^g, 0C(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)0R^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the Ci_-4 alkyl, Ci_-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C₃- 10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

Rⁿ is selected from cyano, halo, Ci_-4 alkyl, C_{3- 10} cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C₆-io aryl-Ci-₄ alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-6 membered heteroaryl)-Ci-₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, Ci-₄ haloalkyl, R°, NHOR⁰, OR⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR⁰C(=NR°)NR°R⁰, S(0)R°, S(0)NR°R°, S(0)₂R°, NR°S(0)₂R°, NR⁰S(0)₂NR⁰R°, or S(0)₂NR°R°, wherein the Ci_-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C₆-io aryl, 5-6 membered heteroaryl, C₆-io aryl-Ci_-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl and C_1-4 haloalkyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^g is selected from hydrogen, Ci_-6 alkyl, Ci_-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl -Ci -₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- io cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

R^p is selected from halo, cyano, C_l-6 alkyl, C_l-6 haloalkyl, C_l-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C₆-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, OC(0)R^r, OC(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)OR^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=N CN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, Ci-₆ haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_{3 i}o cycloalkyl-Ci-₄ alkyl-, (5- 10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1 , 2 or 3 R^q substituents;

R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C₆-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C1-4 haloalkyl, C2-4 alkenyl, or C2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^q is selected from hydroxy, cyano, amino, halo, COOH, Ci-₆ haloalkyl, Ci-₆ alkyl, Ci-₆ alkoxy, Ci- ₆ alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C1-4 haloalkoxy, wherein the C_l-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci-6 alkyl.

5. A compound of Formula V

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein R₅ is selected from C1-4 alkyl, cyano, or Ci_-4 haloalkyl;

R4 is selected from hydrogen, Ci_-6 alkyl, -C(0)0R_ai, C(0)NRbiR_ci, C5-6 aryl, or Ci_-6 heteroaryl; wherein Ci_-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NRMR_C1, C5-6 aryl, and Ci_-6 heteroaryl; R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

Ri, R₂, R₃,R₆, and R₇ are independently selected from hydrogen, halo, Ci_-6 alkyl, C2-6 alkenyl, C_2- ₆ alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO2, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC(=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C₆-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5- 14 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^a is selected from hydrogen, cyano, Ci_-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci- 4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C_3- 10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)- Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^cR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-₄ haloalkyl, C_1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl) -C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- C1-4 alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^c is selected from hydrogen, Ci_-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl -Ci -₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C_l-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- _l0 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent; R^f is selected from Ci_-4 alkyl, Ci_-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- Ci-₄ alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)0R^g, 0C(0)R^g, 0C(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)0R^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)₂NR^gR^g; wherein the C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents;

R^g is selected from hydrogen, Ci_-6 alkyl, C_1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- ₁₀ cycloalkyl -Ci -₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C_l-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- _l0 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-₄ alkyl- are optionally substituted with 1, 2, or 3 R^p substituents;

R^p is selected from halo, cyano, C_l-6 alkyl, C_l-6 haloalkyl, C_l-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)OR^r, 0C(0)R^r, 0C(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)0R^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=N CN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR^rS(0)₂NR^rR^r or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, Ci-₆ haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_{3 i}o cycloalkyl-Ci-₄ alkyl-, (5- 10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents;

R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C_1-4 alkyl, C_3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, Ci-₄ haloalkyl, C_2-4 alkenyl, or C_2-4 alkynyl, wherein the C_1-4 alkyl, C_3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C_2-4 alkenyl, and C_2-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^qis selected from hydroxy, cyano, amino, halo, COOH, Ci-₆ haloalkyl, Ci-₆ alkyl, Ci-₆ alkoxy, Ci- ₆ alkylthio, C_5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C_3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C_1-4 haloalkoxy, wherein the C_l-6 alkyl, C_5-6 aryl, C_3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C_1-4 alkyl, C_1-4 alkoxy, C_1-4 haloalkyl, C_1-4 haloalkoxy, C_5-6 aryl, C_3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci -₆ alkyl.

6. A compound of Formula VI

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein R₅ is selected from Ci-4 alkyl, cyano, or Ci-4 haloalkyl; R4 is selected from hydrogen, Ci_-6 alkyl, -C(0)0R_ai, C(0)NRbiR_ci, C5-6 aryl, or Ci_-6 heteroaryl; wherein Ci_-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NR_biR_ci, C5-6 aryl, and Ci_-6 heteroaryl; R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci_-6 alkyl;

Ri, R₂, R₃,R₆, and R₇ are independently selected from hydrogen, halo, Ci_-6 alkyl, C2-6 alkenyl, C_2- ₆ alkynyl, Ci_-6 haloalkyl, Ci_-6 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO2, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC(=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5- 14 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents;

R^a is selected from hydrogen, cyano, Ci_-6 alkyl, C_1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci- 4 alkyl-, C_3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C_3- ₁₀ cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;

R^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)- Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^cR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-4 haloalkyl, Ci-4 haloalkoxy, C₆-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl) -C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;

R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- Ci-₄ alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)OR^e, OC(0)R^e, OC(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)OR^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^c is selected from hydrogen, Ci_-6 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl -Ci -4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C_l-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- _l0 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent;

R^f is selected from C1-4 alkyl, C1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- C1-4 alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or

R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, C_1-4 alkyl, C_3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C_1-4 haloalkyl, C_2-4 alkenyl, or C2-4 alkynyl, wherein the Ci-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents;

R^q is selected from hydroxy, cyano, amino, halo, COOH, Ci-₆haloalkyl, Ci_-6 alkyl, Ci-₆ alkoxy, Ci- ₆ alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C1-4 haloalkoxy, wherein the Ci_-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R⁸ is Ci -₆ alkyl.

(S)-l-((7-((2-methyl-[ 1, 1 '-biphenyl] -3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl) piperidine-2-carboxylic acid (1),

N-(2-(((5-methoxy-7-((2-methyl-[ l, l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl) methyl)amino)ethyl)acetamide (2),

(S)-l-((7-((3-(l-(3-(3,3-difluoropyrrolidin-l-yl)propyl)-lH-indol-4-yl)-2-methylbenzyl)oxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (3),

(S)-l-((6-methyl-7-((2-methyl-[ 1, 1 '-biphenyl] -3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)piperidine-2-carboxylic acid (4),

(S)-l-((6-chloro-7-((2-methyl-[ 1, 1 '-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)piperidine-2-carboxylic acid (5),

Methyl 7-(((2-acetamidoethyl)amino)methyl)-4-((2-methyl-[ l, l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-indene-5-carboxylate (6),

(S)-l-((7-((3'-(3-(3,3-difluoropyrrolidin-l-yl)propoxy)-2,2'-dimethyl-[l , l'-biphenyl]-3- yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (7), (S)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[ l , l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)piperidine-2-carboxylic acid (8),

(S)-l-((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[ l, l'-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (9) N-(2-(((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (10)

(S)-5-((5-methoxy-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (11)

(S)-l-((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-5-(2, 2, 2-trifluoroethoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)piperidine-2-carboxylic acid (12)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)amino)ethyl)-N-methylacetamide(l3)

N-(2-(((5-(l-(3-cyanophenyl)ethoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (14)

N-(l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)piperidin-3-yl)acetamide (15)

N-(2-(((7-((2-methyl-[l, r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)ethyl)acetamide (16)

6-((7-((2-methyl-[l, l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)-2-oxa-6- azaspiro[3.3]heptane (17)

2-(hydroxymethyl)-2-(((7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)propane- 1 ,3-diol (18)

l-(((7-((2-methyl-[l, l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)cyclopropane-l -carboxylic acid (19)

((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)glycine (20)

3-(((7-((2-methyl-[l, l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)propanoic acid (21)

N-methyl-N-((7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)glycine (22)

3-(((7-((2-methyl-[l, l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)butanoic acid (23)

((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)alanine (24) (2S,4R)-4-hydroxy-l-((5-methoxy-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (25) (S)-l-((5-methoxy-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)piperidine-2-carboxylic acid (26)

l-((4-((2-methyl-[l, r-biphenyl]-3-yl)methoxy)-5,6,7,8-tetrahydronaphthalen-l- yl)methyl)piperidine-2-carboxylic acid (27)

N-(2-(((6-methyl-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)ethyl)acetamide (28)

(2S,4R)-4-hydroxy-l-((6-methyl-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (29)

N-(2-(((6-chloro-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)ethyl)acetamide (30)

(2S,4R)-l-((6-chloro-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (31)

N-(2-(((7-((3'-(3-(3,3-difluoropyrrolidin-l-yl)propoxy)-2,2'-dimethyl-[l, r-biphenyl]-3- yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (32) (2S,4R)-l-((7-((3'-(3-(3,3-difluoropyrrolidin-l-yl)propoxy)-2,2'-dimethyl-[l,r-biphenyl]-3- yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (33)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)amino)ethyl)acetamide (34)

(2S,4R)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (35)

(S)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)piperidine-2-carboxylic acid (36)

(S)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)piperidine-2-carboxamide (37)

3-(((4-((( 1 ,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-7-((2-methyl-[ 1 , G- biphenyl] -3-yl)methoxy)-2, 3-dihydro- lH-inden-5-yl)oxy)methyl)benzonitrile (38)

3-(((4-((2-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)- 2,3-dihydro- lH-inden-5-yl)oxy)methyl)benzonitrile (39)

3-(((4-((3-hydroxypiperidin-l-yl)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro- lH-inden-5-yl)oxy)methyl)benzonitrile (40) ((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)glycine (41)

(S)-5-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (42)

rac-(lR,6S)-2-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l, l'-biphenyl]-3-yl) methoxy)-2,3- dihydro- lH-inden-4-yl)methyl)-2-azabicyclo[4.1.0]heptane- 1 -carboxylic acid

(cis, racemic) (43)

4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-2, 3-dihydro- lH-inden-

4-yl)methyl)amino)butanoic acid (44)

(lR,6S)-2-((5-methoxy-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-2,3-dihydro-lH-inden-4-yl) methyl)-2-azabicyclo [4. l.0]heptane-l -carboxylic acid (cis, racemic) (45)

(S)-l-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl) methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (46)

(2S,4R)-l-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro- 1 H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (47)

N-(2-(((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3- dihydro- 1 H-inden-4-yl)methyl)amino)ethyl)acetamide (48)

5-(((4-((( 1 ,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-7-((2-methyl-[ 1 , G- biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-5-yl)oxy)methyl)nicotinonitrile (49)

(S)-4-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)morpholine-3-carboxylic acid (50)

rac-(lR,6S)-2-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)- 2, 3-dihydro- lH-inden-4-yl)methyl)-2-azabicyclo[4.l.0]heptane-l -carboxylic acid (cis, racemic)

(51)

(S)-5-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (52)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)(methyl)amino)ethyl)acetamide (53)

N-(2-(((5-((4-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-4-yl)methyl)amino)ethyl)acetamide (54) (S)-l-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)piperidine-2-carboxylic acid (55)

N-(2-(((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)amino)ethyl)acetamide (56)

(2S ,4R)- 1 -((7-((2-cyano- [ 1 , G -biphenyl] -3 -yl)methoxy)-5 -methoxy-2,3 -dihydro- 1 H-inden-4- yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (57)

3-(((7-(((l,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-6-methoxy-2, 3-dihydro- lH-inden-4-yl)oxy)methyl)-[ 1 , 1 '-biphenyl] -2-carbonitrile (58)

(S)-4-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)morpholine-3-carboxylic acid (59)

((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)glycine (60)

(S)-5-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (61)

rac-(lR,6S)-2-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)-2-azabicyclo[4.l.0]heptane-l -carboxylic acid (cis, racemic) (62)

2-(l-((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)piperidin-2-yl)acetic acid (63)

N-(2-(((7-((2-cyano-[l,l'-biphenyl]-3-yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4- yl)methyl)(methyl)amino)ethyl)-N-methylacetamide (64)

5-((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-5-yl)oxy)pentanoic acid (65)

5-((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-5-yl)oxy)pentanamide (66)

(S)-l-((5-(4-carboxybutoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-

4-yl)methyl)piperidine-2-carboxylic acid (67)

(S)-l-((5-((5-amino-5-oxopentyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (68)

(S)-l-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[l,r-biphenyl]-3-yl) methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (69) (2S,4R)-l-((7-((2-cyano-[l,r-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3-yl)methoxy)-2,3- dihydro- 1 H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (70)

(R)- 1 -((7 -((2-cyano- [ 1 , G -biphenyl] -3 -yl)methoxy)-5 -((5 -cyanopyridin-3 -yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-3-carboxylic acid (71)

rac-(lR,6S)-2-((7-((2-cyano-[l,r-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3-yl)methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)-2-azabicyclo[4.l.0]heptane-l -carboxylic acid (cis racemic) (72)

Methyl 4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)amino)bicyclo[2.2.2]octane-l-carboxylate (73)

4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden- 4-yl)methyl)amino)bicyclo[2.2.2]octane-l-carboxylic acid (74)

(S)-l-((5-methoxy-7-((2-(trifluoromethyl)-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden- 4-yl)methyl)piperidine-2-carboxylic acid (75)

(2S ,4R)-4-hydroxy- 1 -((5 -methoxy-7-((2-(trifluoromethyl)- [ 1 , 1 '-biphenyl] -3 -yl)methoxy)-2, 3- dihydro-lH-inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (76)

(2S)- 1 -((7-((2-methyl-[ 1 , G-biphenyl] -3-yl)methoxy)-5-(( 1 -methylpiperidin-3-yl)methoxy)-2,3- dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (77)

(S)-l-((5-(4-carboxybutoxy)-7-((2-cyano-[l, l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden- 4-yl)methyl)piperidine-2-carboxylic acid (78)

N-(2-(((5-(4-cyanobutoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)amino)ethyl)acetamide (79)

(S)-l-((5-(4-cyanobutoxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)piperidine-2-carboxamide (80)

(2S,4R)- 1 -((5-(4-cyanobutoxy)-7-((2-methyl- [1,1 '-biphenyl] -3-yl)methoxy)-2, 3-dihydro- 1 H- inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (81)

(S)-l-((5-(((lS,2R)-2-carboxycyclopropyl)methoxy)-7-((2-methyl-[l,l'-biphenyl]-3- yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (82)

(lR,2S)-2-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l, l'-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-5-yl)oxy)methyl)cyclopropane- 1 -carboxylic acid (83)

(S)-l-((7-((3-(2,3-dihydrobenzo[b][l,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methoxy-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (84) (2S,4R)-l-((7-((3-(2,3-dihydrobenzo[b][l,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methoxy-2,3- dihydro- lH-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (85)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2,2'-dimethyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1 H-inden-4-yl)methyl) amino)ethyl) acetamide (86)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((4'-fluoro-2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)amino)ethyl)acetamide (87)

(S)-l-((5-((3-carbamoylbenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2,3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (88)

3-(((4-(aminomethyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-5- yl)oxy)methyl)benzonitrile (89)

N-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]-3-yl) methoxy)-2, 3-dihydro- lH-inden-

4-yl)methyl)acetamide (90)

6-acetamido-N-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro- 1 H-inden-4-yl)methyl)hexanamide (91)

3-(((4-((dimethylamino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- 1H- inden-5-yl)oxy)methyl)benzonitrile (92)

5-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-5-yl)oxy)methyl)nicotinic acid (93)

5-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-5-yl)oxy)methyl)nicotinamide (94)

3-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[l,r-biphenyl] -3-yl)methoxy)-2,3- dihydro-lH-inden-5-yl)oxy)methyl)benzamide (95)

(S)-l-((3-methoxy-l-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-6,7-dihydro-5H- cyclopenta[c]pyridin-4-yl)methyl)piperidine-2-carboxylic acid (96)

N-(2-(((3-methoxy-l-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-6,7-dihydro-5H- cyclopenta[c]pyridin-4-yl)methyl)amino)ethyl)acetamide (97)

(S)-4-((5-methoxy-7-((2-methyl-[l,r-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl)morpholine-3-carboxylic acid (98)

5-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[ l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-

4-yl)methyl)-4,5,6,7-tetrahydro-lH-pyrazolo[4,3-c]pyridine-3-carboxylic acid (99)

8. A process of preparation of compounds of Formula I, as claimed in claim 1 or its polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof.

wherein the Xi of Formula I (a) and Formula I is selected from -CH₂0-, -OCH2-, -C(0)NH- or - NHC(O)-; R4 of Formula I (a) and Formula I is selected from hydrogen, Ci-₆ alkyl, -C(0)0R_ai, C(0)NRbiRci, C5-6 aryl, or Ci-₆ heteroaryl, wherein Ci-₆ alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R_ai, C(0)NR_biR_ci, C5-6 aryl, and Ci-₆ heteroaryl; R_ai, R_bi, and R_ci are independently selected from hydrogen or Ci-₆ alkyl;X of Formula I (a) and Formula I is selected from CR3 or N; Ri, R2, R₆, and R₇ of Formula I (a) and Formula I are independently selected from hydrogen, halo, Ci-₆ alkyl, C2- ₆ alkenyl, C2-6 alkynyl, Ci-₆ haloalkyl, Ci-₆ haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5- 14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, NO2, OR^a, SR^a, NHOR^a, C(0)R^a, C(0)NR^aR^a, C(0)0R^a, 0C(0)R^a, 0C(0)NR^aR^a, NHR^a, NR^aR^a, NR^aC(0)R^a, NR^aC(0)0R^a, NR^aC(0)NR^aR^a, C(=NR^a)R^a, C(=NR^a)NR^aR^a, NR^aC(=NR^a)NR^aR^a, NR^aS(0)R^a, NR^aS(0)₂R^a, NR^aS(0)₂NR^aR^a, S(0)R^a, S(0)NR^aR^a, S(0)₂R^a, or S(0)₂NR^aR^a, wherein the Ci-₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5- 14 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R^b substituents; R^a is selected from hydrogen, cyano, Ci-₆ alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl-Ci-4alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substituents;R^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4- 10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR^c, OR^c, SR^C, C(0)R^c, C(0)NR^cR^c, C(0)OR^c, OC(0)R^c, OC(0)NR^cR^c, C(=NR^C)NR^CR^C, NR^CC(=NR^C)NR^CR^C, NHR^C, NR^CR^C, NR^cC(0)R^c, NR^cC(0)OR^c, NR^cC(0)NR^cR^c, NR^cS(0)R^c, NR^cS(0)₂R^c, NR^cS(0)₂NR^cR^c, S(0)R^c, S(0)NR^cR^c, S(0)₂R^C or S(0)₂NR^cR^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-4 haloalkyl, C1-4 haloalkoxy, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl) -C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R^d substituents;R^c is selected from hydrogen, Ci_-6 alkyl, C 1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)- Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-₄ alkyl-, wherein the Ci_-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)- Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R^f substituent;

R^d is selected from cyano, amino, Ci_-6 alkyl, Ci_-6 haloalkyl, halo, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, (4-10 membered heterocycloalkyl)- C_1-4 alkyl-, NHOR^e, OR^e, SR^e, C(0)R^e, C(0)NR^eR^e, C(0)0R^e, 0C(0)R^e, 0C(0)NR^eR^e, NHR^e, NR^eR^e, NR^eC(0)R^e, NR^eC(0)NR^eR^e, NR^eC(0)0R^e, C(=NR^e)NR^eR^e, NR^eC(=NR^e)NR^eR^e, NR^eC(=NOH)NR^eR^e, NR^eC(=NCN)NR^eR^e, S(0)R^e, S(0)NR^eR^e, S(0)₂R^e, NR^eS(0)₂R^e, NR^eS(0)₂NR^eR^e, or S(0)₂NR^eR^e, wherein the Ci_-6 alkyl, Ci_-6 haloalkyl, C_6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl) -C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^f substituents;

R^f is selected from C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)- Ci-₄ alkyl-, halogen, CN, NHOR^g, OR^g, SR^g, C(0)R^g, C(0)NR^gR^g, C(0)OR^g, OC(0)R^g, OC(0)NR^gR^g, NHR^g, NR^gR^g, NR^gC(0)R^g, NR^gC(0)NR^gR^g, NR^gC(0)OR^g, C(=NR^g)NR^gR^g, NR^gC(=NR^g)NR^gR^g, S(0)R^g, S(0)NR^gR^g, S(0)₂R^g, NR^gS(0)₂R^g, NR^gS(0)₂NR^gR^g, or S(0)2NR^gR^g; wherein the C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 Rⁿ substituents; R^g is selected from hydrogen, Ci-₆ alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- 10 cycloalkyl -Ci -4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci-₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-4 alkyl-, C3- _l0 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R^p substituents; Rⁿ is selected from cyano, halo, C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ci-₄ haloalkyl, R°, NHOR⁰, OR⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR⁰C(=NR°)NR°R⁰, S(0)R°, S(0)NR°R°, S(0)₂R°, NR°S(0)₂R°, NR⁰S(0)₂NR⁰R°, or

S(0)₂NR°R°, wherein the C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-io aryl, 5-6 membered heteroaryl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl and C1-4 haloalkyl are optionally substituted with 1, 2 or 3 R^q substituents; R^p is selected from halo, cyano, Ci-₆ alkyl, Ci-₆ haloalkyl, Ci-₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C_6- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl- Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1 -₄ alkyl-, NHOR^r, OR^r, SR^r, C(0)R^r, C(0)NR^rR^r, C(0)0R^r, 0C(0)R^r, 0C(0)NR^rR^r, NHR^r, NR^rR^r, NR^rC(0)R^r, NR^rC(0)NR^rR^r, NR^rC(0)0R^r, C(=NR^r)NR^rR^r, NR^rC(=NR^r)NR^rR^r, NR^rC(=NOH)NR^rR^r, NR^rC(=N CN)NR^rR^r, S(0)R^r, S(0)NR^rR^r, S(0)₂R^r, NR^rS(0)₂R^r, NR'S(0)₂NR'R' or S(0)₂NR^rR^r, wherein the Ci_-6 alkyl, Ci-e haloalkyl, Ci-e haloalkoxy, C_2-6 alkenyl, C_2-6 alkynyl, C_6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-io aryl-Ci-₄ alkyl-, C3-10 cycloalkyl-Ci-₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R^q substituents; R^e, R¹, R^k, R° and R^r are independently selected from hydrogen, Ci- 4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, Ci -4 haloalkyl, C_2-4 alkenyl, or C_2-4 alkynyl, wherein the C_l-4 alkyl, C3-6 cycloalkyl, C_6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C₂-4 alkenyl, and C₂-4 alkynyl are optionally substituted with 1, 2 or 3 R^q substituents; R^q is selected from hydroxy, cyano, amino, halo, COOH, Ci_-6 haloalkyl, Ci_-6 alkyl, Ci_-6 alkoxy, Ci_-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR⁸, NR⁸R⁸, and C 1-4 haloalkoxy, wherein the C_l-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C_l-4 alkyl, C_l-4 alkoxy, C1-4 haloalkyl, C_l-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R⁸ is C_l-6 alkyl; m is 1 or 2; Ring A is selected from substituted or unsubstituted C5-10 aryl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted 6-10 membered monocyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O; Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O, with substituted amines in the presence of solvents to obtain compounds of Formula I.

12. A method for the treatment and/or prevention of various diseases, including cancer and infectious diseases, comprising administering to a subject suffering from the proliferative disorder or cancer a therapeutically effective amount of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI as claimed in any one of claims 1 - 7 or the pharmaceutical composition as claimed in claim 10, or 1 1, with other clinically relevant cytotoxic agents or non-cytotoxic agents to a subject in need thereof.

14. A method for the treatment of cancer, said method comprising administering a combination of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI as claimed in any of claims 1 - 7 or the pharmaceutical composition as claimed in claim 10 or 11, with other clinically relevant cytotoxic agents or non-cytotoxic agents to a subject in need thereof. 16. A method of treatment of cancer, said method comprising administering a combination of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI as claimed in any of claims 1 - 7, or the pharmaceutical composition as claimed in claim 10 or 11, with other clinically relevant immune modulators agents to a subject in need of thereof.

Description:

BICYCLIC COMPOUNDS AS INHIBITORS OF PD1/PD-L1

INTERACTION/ACTIVATION

TECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates to substituted bicyclic compounds of Formula I along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof which are inhibitors of PD1/PD-L1 interaction. The present invention also relates to method of synthesizing the compounds of Formula

Formula (I)

[0002] The compounds described herein are inhibitors of PD1/PD-L1 activation and may be used in the treatment of cancer, and other diseases or conditions associated with activation of PD 1/PD-L1.

BACKGROUND OF THE INVENTION

[0003] Tumour development and survival involves the interplay between cancer cells, normal stromal cells and host defence mechanisms (Vinay D.S . et al. , Seminars in Cancer Biology, 2015, 35: S 185-S 198). Generally, CD8+ cytotoxic T cells (CTLs) and CD4+ helper T (Thl) cells curb cancer development via mechanisms commonly involving the production of interferon (IFN)-y and cytotoxins (Zamarron BF et al, Intl. J. Biol. Sciences, 2011, 7(5):65l-658). Tumours have, however evolved a number of mechanisms to escape immune eradications. The PD-1/PD-L1 molecular pathway is one such primary mechanism of cancer immune evasion.

[0004] PD-l is a type 1 trans-membrane protein encoded by the PDCD1 gene. It is a member of the extended CD28/CTLA-4 immunoglobulin family and one of the most important inhibitory co-receptors expressed by T cells (He et al., Scientific Reports, 2015, 5: 1-9). PD-l is absent on resting T cells but is induced on activated T cells. It is also expressed on B cells, NK cells, dendritic cells (DCs) and macrophages. The programmed cell death protein (PD-l) down regulates the immune system and prevents it from killing cancerous cells present in the body. In cancer, high levels of PD-l are detected in tumour infiltrating T cells and this expression has been associated with impaired CD8+ T cell function (Leung J et al., Immune Network, 2014, l4(6):265-276).

[0005] PD-l has two ligands: PD-L1 (also named B7-H1; CD274) and PD-L2 (B7-DC; CD273), that are both co-inhibitory (Flies D.B .et al, Yale J. Biology Medicine, 2011, 84(4):409-42l). PD-L1, expressed on almost all murine tumour cells, is the major ligand for PD-l mediated immune suppression. It is constitutively expressed on APCs and can be broadly induced on cells in both lymphoid tissues and non-lymphoid peripheral tissues following cellular activation (Flies D.B .et al, Yale J. Biology Medicine, 2011, 84(4):409-42l; Dong Y .et al., Oncotarget, 2017, 8(2):2171-2186). The cytokine IFN-g is particularly effective in up-regulating PD-L1 expression due to IFN-g response elements in the PD-L1 promoter region (Lee S.J.ei al., FEBS Letters, 2006, 580:755- 762; Flies D.B .et al., Immunotherapy, 2007, 30(3):251-260). The expression of B7- DC/PD-L2 is largely restricted to myeloid dendritic cells (DCs) and macrophages in lymphoid compartments and is not broadly expressed in peripheral tissues (Flies D.B .et al, Yale J. Biology Medicine, 2011, 84(4):409-42l). In cancer, PD-L1 is expressed on the surface of tumour cells in various solid malignancies such as squamous cell carcinoma of the head and neck, melanoma, carcinomas of the brain, thyroid, thymus, esophagus, lung, breast, gastrointestinal tract, colorectum, liver, pancreas, kidney etc. (Topalian S.L.ei al, Curr. Opin. Immunol., 2012, 24(2):207-2l2; Wang X.et al, Oncotargets and Therapy, 2016, 9:5023-5039). In hepatocellular carcinoma, melanoma and breast cancer, PD-L1 positivity was correlated with worse prognosis (Muenst S .et al., Breast Cancer Res. Treat., 2014, 146(1): 15-24; Leung et al., Immune Network, 2014, l4(6):265-276; Wang Q .et al., Medicine (Baltimore), 2017, 96(18): e6369). In contrast, normal human tissues seldom express PD-L1 protein on their cell surface, indicating that PD-L1 can be a selective target for anti-tumour therapy (Chen L .et al., J. Clin. Invest., 2015, l25(9):3384-339l).

[0006] Cancer microenvironment manipulates the PD-1/PD-L1 pathway; induction of PD-L1 expression is associated with inhibition of immune responses against cancer, thus permitting cancer progression and metastasis (He Let al., Scientific Reports, 2015, 5: 1- 9; Bardhan K .et al., Frontiers in Immunology, 2016, 7(550): l-l7). Activation of PD- 1/PD-L1 pathway induces apoptosis of activated T cells (Dong Li.et al., Nature Medicine, 2002, 8(8):793 - 800; Curiel T. J. et al., Nature Medicine, 2003, 9(5):562 - 567), facilitates T cell anergy and exhaustion (Barber D. L. et al., Nature, 2005, 439(7077):682- 687), enhances the function of regulatory T cells (Francisco L.M. et al., J. Exp. Med., 2009, 206(13):3015-3029) and inhibits the proliferation of T cells (Sheppard K.A. et ah, FEBS Letters, 2004, 574:37-4 l;Patsoukis N .et al, Cell Cycle, 2012, l l(23):4305-4309). Therefore, blocking this pathway restores the proliferation and cytotoxicity of CTLs, inhibiting the function of regulatory T cells (Tregs), and results in decrease T cell apoptosis.

[0007] Blockade of the PD-1/PD-L1 pathway by therapeutic antibodies has been shown to prevent inhibitory signalling from cancer cells and enabling CTLs to elicit an immune response against the target/cancer cells (Zou W .et ah, Sci. Transl. Med., 2016, 8(328):328rv4; Smahel M., Int. J. Mol. Sci., 2017, 18(6): 1331). A number of cancer immunotherapy agents targeting PD-l have been developed till date and approved for a number of malignancies including melanoma, lung cancer, kidney cancer, Hodgkin’s lymphoma, head and neck cancer and urothelial cancer. The first therapeutic anti-PD-Ll antibody was approved by the FDA in May 2016, for the treatment of patients with metastatic urothelial carcinoma and non-small cell lung cancer, with a number of additional therapies in the pipeline. Currently, there are at least 500 clinical studies on going with PD-1/PD-L1 antibodies against 20 types of solid and haematological malignant tumours. However, there is still a need for potent and selective small molecule inhibitors of the PD-1/PD-L1 pathway.

[0008] Common drug-related adverse effects (AEs) of both anti-PD-l and anti-PD-Ll antibodies include fatigue, rash, diarrhoea, pruritus, decrease appetite, arthralgia and nausea. Immune-related AEs (irAEs) such as dermatitis, colitis, hepatitis, vitiligo and thyroiditis have been reported and about 10% of patients develop grade 3 or 4 irAEs (Hamanishi J .et ah, Int. J. Clin. Oncol., 2016, 21:462-473). The long residence time of the monoclonal antibodies (mAbs) could contribute to these AEs, which may be partially circumvented using a small molecule inhibitor. In addition, studies using smaller cell penetrating biologicals and DNA aptamers have shown to exert antibody-mimic functions and are advantageous over antibody for its chemically synthetic nature, low immunogenicity, and efficient tissue penetration (Lai W.Y .et ah, Mol. Therapy - Nucl. Acids, 2016, 5: e397). Small molecule inhibitors, therefore, can provide increased oral bioavailability, increased bio-efficiency and shortened half-life activity for a more controllable treatment, particularly in the case of auto-immune or other adverse events.

[0009] As discussed, the PD-1/PD-L1 inhibitory compounds have vast utility in up- regulating the immune system for efficiently combating cancer. Therefore, the identification of a chemical moiety, especially small molecule inhibitors, that facilitates this inhibition is necessary. Therefore, the identification and development of new PD- 1/PD-L1 inhibitor compounds treating cancer and other diseases or conditions associated with activation of PD-1/PD-L1 would open new opportunities in the realm of cancer treatment.

SUMMARY OF INVENTION

[00010] In an aspect of the present discosure there is provided a compound of Formula I

Formula (I)

OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci_ ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocyclo alkyl) -Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, Ci- ₄ alkyl, C _2-4 alkenyl, C _2-4 alkynyl, Ci- ₄ haloalkyl, Ci- ₄ haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the Ci- ₄ alkyl, C _2-4 alkenyl, C _2-4 alkynyl, Ci- ₄ haloalkyl, Ci-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^d is selected from cyano, amino, Ci _-6 alkyl, Ci _-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci_ ₄ alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl- Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents;

R ^f is selected from C alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci_ ₄ alkyl, C 1-4 haloalkyl, C ₂-6 alkenyl, C ₂-6 alkynyl, C6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ^g is selected from hydrogen, C1-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ⁿ is selected from cyano, halo, C14 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, C1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C 1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the C 1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- 10 aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, C1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and C1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^p is selected from halo, cyano, C 1-6 alkyl, C 1-6 haloalkyl, C1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)0R ^r, 0C(0)R ^r, 0C(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)0R ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2- 4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci- ₆ haloalkyl, Ci _-6 alkyl, C i-r, alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl,

4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C14 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is Ci _-6 alkyl; m is 1 or 2; Ring A is selected from substituted or unsubstituted C5-10 aryl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O; Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

[00011] In another aspect of the present disclosure there is provided a compound of Formula II

Formula II

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH ₂0-, -OCH ₂-, -C(0)NH- or -NHC(O)-;

R ₄ is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C _5- ₆ aryl, or Ci _-6 heteroaryl, wherein Ci _-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NRbiRci, C5-6 aryl, and Ci _-6 heteroaryl;

R _ai, R _bi, and R _ci are independently selected from hydrogen or Ci _-6 alkyl;

R ₅ is selected from C _1-4 alkyl, cyano, or C _1-4 haloalkyl;

Ri, R ₂, R ₃, R ₆, and R ₇ are independently selected from hydrogen, halo, Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents;

R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents;

R ^b is selected from halo, hydroxy, cyano, amino, nitro, C ₁₄ alkyl, C ₂-4 alkenyl, C ₂-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)0R ^c, 0C(0)R ^c, 0C(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)0R ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the Ci- ₄ alkyl, C _2-4 alkenyl, C _2-4 alkynyl, Ci- ₄ haloalkyl, Ci- ₄ haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents;

R ^f is selected from C alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocyclo alkyl) -Ci- ₄ alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci_ ₄ alkyl, Ci-4haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents;

R ⁿ is selected from cyano, halo, C _1-4 alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R°, or S(0) ₂NR°R°, wherein the C ₁ alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- 10 aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and C _1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^g is selected from hydrogen, Ci _-6 alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents;

R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-C _1-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, Ci _-6 alkyl, Ci _-6 alkoxy, Ci _-6 alkylthio, C _5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C _3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C _1-4 haloalkoxy, wherein the Ci _-6 alkyl, C _5-6 aryl, C _3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _5-6 aryl, C _3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R ⁸ is Ci- ₆ alkyl;

Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

[00012] In yet another aspect of the present disclosure there is provided a compound of Formula III

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein Xi is selected from -CH ₂0-, -OCH2-, -C(0)NH- or -NHC(O)-;

R ₄ is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C ₅- ₆ aryl, or Ci _-6 heteroaryl; wherein Ci _-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NRbiRci, C5-6 aryl, and Ci _-6 heteroaryl;

R _ai, R _bi, and R _ci are independently selected from hydrogen or Ci _-6 alkyl;

R5 is selected from C1-4 alkyl, cyano, or C1-4 haloalkyl; Ri, R ₂, R ₃,R ₆, and R ₇ are independently selected from hydrogen, halo, Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents;

R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci-4alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents;

R ^b is selected from halo, hydroxy, cyano, amino, nitro, C ₁ alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents;

R ^d is selected from cyano, amino, Ci _-6 alkyl, Ci _-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^e, 0R ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)0R ^e, 0C(0)R ^e, 0C(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)0R ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci _-6 alkyl, Ci-r, haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl- C1-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents;

R ^c is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent;

R ⁿ is selected from cyano, halo, C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C ₂-6 alkenyl, C ₂-6 alkynyl, C 1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R°, or S(0) ₂NR°R°, wherein the C 1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- 10 aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and Ci-4haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^g is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents;

R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, Ci _-6 alkyl, Ci _-6 alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C 1-4 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C 1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R ⁸ is C1-6 alkyl.

[00013] In an aspect of the present discosure there is provided a compound of Formula IV

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

whereinR ₅ is selected from C alkyl, cyano, or C _1-4 haloalkyl;

Ri, R ₂, R3,R6, and R ₇ are independently selected from hydrogen, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents;

R ^a is selected from hydrogen, cyano, C _1-6 alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents;

R ^b is selected from halo, hydroxy, cyano, amino, nitro, Cw alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents;

R ^c is selected from hydrogen, C _1-6 alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from Ci alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci_ ₄ alkyl, C 1-4 haloalkyl, C ₂-6 alkenyl, C ₂-6 alkynyl, C6-ioaryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents;

R ⁿ is selected from cyano, halo, C _1-4 alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)-Ci- ₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the C ₁ alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- 10 aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and C _1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^g is selected from hydrogen, Ci _-6 alkyl, C 1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents;

R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)0R ^r, 0C(0)R ^r, 0C(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)0R ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, Ci _-6 alkyl, Ci _-6 alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C 1-4 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C 1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R ⁸ is Ci- ₆ alkyl.

[00014] In an aspect of the present disclosure there is provided a compound of Formula V

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein R5 is selected from CM alkyl, cyano, or C1-4 haloalkyl; R ₄ is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C _5- ₆ aryl, or Ci _-6 heteroaryl; wherein Ci _-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NRbiRd, C5-6 aryl, and Ci _-6 heteroaryl;

R _ai, R _bi, and R _ci are independently selected from hydrogen or Ci _-6 alkyl;

R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents;

R ^b is selected from halo, hydroxy, cyano, amino, nitro, C14 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents;

R ^g is selected from hydrogen, C _1-6 alkyl, C 1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents;

R ^p is selected from halo, cyano, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the C1-6 alkyl, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C _2-4 alkenyl, or C _2-4 alkynyl, wherein the C _1-4 alkyl, C _3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C _2-4 alkenyl, and C _2-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci- ₆ haloalkyl, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio, C _5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C _3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C _1-4 haloalkoxy, wherein the C _1-6 alkyl, C _5-6 aryl, C _3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _5-6 aryl, C _3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R ⁸ is C _1-6 alkyl.

[00015] In an aspect of the present disclosure there is provided a compound of Formula VI

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof,

wherein R ₅ is selected from C _M alkyl, cyano, or C _1-4 haloalkyl;

R ₄ is selected from hydrogen, hydroxyl, C _1-6 alkyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C _5- ₆ aryl, or C _1-6 heteroaryl; wherein C _1-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NRbiRd, C5-6 aryl, and C1-6 heteroaryl;

R _ai, R _bi, and R _ci are independently selected from hydrogen or C _1-6 alkyl;

Ri, R ₂, R ₃,R ₆, and R ₇ are independently selected from hydrogen, halo, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-14 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents;

R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents;

R ^b is selected from halo, hydroxy, cyano, amino, nitro, C ₁ alkyl, C ₂-4 alkenyl, C ₂-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents;

R ^d is selected from cyano, amino, Ci _-6 alkyl, Ci _-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl- Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents;

R ^c is selected from hydrogen, Ci- ₆ alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent;

R ^f is selected from C alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci_ ₄ alkyl, C 1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents;

R ⁿ is selected from cyano, halo, C _1-4 alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)-Ci- ₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, C _1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR ⁰S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the C ₁ alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- 10 aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, C1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and C _1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents;

R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C _1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C2-4 alkenyl, or C2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, Ci _-6 alkyl, Ci _-6 alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C 1-4 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C 1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl;

R ⁸ is Ci- ₆ alkyl. [00016] The present disclosure further describes the process of preparation of compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof.

[00017] The present disclosure also discloses the method for the treatment and/or prevention of various diseases, including cancer and infectious diseases, comprising administering to a subject suffering from the proliferative disorder or cancer a therapeutically effective amount of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or the pharmaceutical composition comprising compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI, with other clinically relevant cytotoxic agents or non-cytotoxic agents to a subject in need thereof.

[00018] The present disclosure further discloses the use of the compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or the pharmaceutical composition comprising compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI, for the treatment and/or prevention of various diseases including proliferative disorder or cancer; or treatment of cancer together with other clinically relevant cytotoxic agents or non-cytotoxic agents.

[00019] The present disclosure also discloses a method for the treatment of cancer, said method comprising administering a combination of the compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or the pharmaceutical composition comprising compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI, with other clinically relevant cytotoxic agents or non- cytotoxic agents to a subject in need thereof.

[00020] The present disclosure further describes a method of treatment of cancer, said method comprising administering a combination of the compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or the pharmaceutical composition, with other clinically relevant immune modulators agents to a subject in need of thereof.

[00021] These and other features, aspects, and advantages of the present subject matter will become better understood with reference to the following description. This summary is provided to introduce a selection of concepts in a simplified form. This summary is not intended to identify key features or essential features of the disclosure, nor is it intended to be used to limit the scope of the subject matter. DETAILED DESCRIPTION

[00022] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any or more of such steps or features.

Definitions

[00023] For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are collected here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.

[00024] The articles“a”,“an” and“the” are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article.

[00025] Throughout the description and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers but not to the exclusion of any other integer or step or group of integers or steps.

[00026] The term“including” is used to mean“including but not limited to”.“Including” and“including but not limited to” are used interchangeably.

[00027] In the structural formulae given herein and throughout the present disclosure, the following terms have been indicated meaning, unless specifically stated otherwise.

[00028] Furthermore, the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, can be its derivatives, analogs, stereoisomers, diastereomers, geometrical isomers, polymorphs, solvates, co-crystals, intermediates, metabolites, prodrugs or pharmaceutically acceptable salts and compositions.

[00029] The compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, and their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof can also be referred as“compounds of the present disclosure”. [00030] The compounds according to Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, may contain one or more asymmetric centers (also referred to as a chiral centers) and may, therefore, exist as individual enantiomers, diastereoisomers, or other stereoisomeric forms, or as mixtures thereof. Chiral centers, such as chiral carbon atoms, may also be present in a substituent such as an alkyl group. Where the stereochemistry of a chiral center present in Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or in any chemical structure illustrated herein, is not specified, the structure is intended to encompass any stereoisomer and all mixtures thereof. Thus, compounds according to Formula I- VI containing one or more chiral centers may be used as racemic modifications including racemic mixtures and racemates, enantiomerically-enriched mixtures, or as enantiomerically-pure individual stereoisomers.

[00031] Compounds disclosed herein include isotopes of hydrogen, carbon, oxygen, fluorine, chlorine, iodine and sulfur which can be incorporated into the compounds, such as not limited to ²H (D), ³H (T), c ^UC, ¹³C, ¹⁴C, ¹⁵N, ¹⁸F, ³⁵S, ³⁶Cl and ¹²⁵I. Compounds of this invention where in atoms were isotopically labeled for example radioisotopes such as ³H, ¹³C, ¹⁴C, and the like can be used in metabolic studies and kinetic studies. Compounds of the invention where hydrogen is replaced with deuterium may improve the metabolic stability and pharmacokinetics properties of the drug such as in vivo half life.

[00032] Individual stereoisomers of a compound according to Formula I- VI which contain one or more asymmetric centers may be resolved by methods known to those skilled in the art. For example, such resolution may be carried out (1) by formation of diastereoisomeric salts, complexes or other derivatives; (2) by selective reaction with a stereoisomer-specific reagent, for example by enzymatic oxidation or reduction; or (3) by gas-liquid or liquid chromatography in a chiral environment, for example, on a chiral support such as silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated that where the desired stereoisomer is converted into another chemical entity by one of the separation procedures described above, a further step is required to liberate the desired form.

[00033] Alternatively, specific stereoisomers may be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer to the other by asymmetric transformation. [00034] It is to be understood that the references herein to compounds of Formula I- VI and salts thereof covers the compounds of Formula I- VI as free bases, or as salts thereof, for example as pharmaceutically acceptable salts thereof. Thus, in one embodiment, the invention is directed to compounds of Formula I- VI as the free base. In another embodiment, the invention is directed to compounds of Formula I- VI and salts thereof. In a further embodiment, the invention is directed to compounds of Formula I- VI and pharmaceutically acceptable salts thereof.

[00035] It will be appreciated that pharmaceutically acceptable salts of the compounds according to Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI, may be prepared. Indeed, in certain embodiments of the invention, pharmaceutically acceptable salts of the compounds according to Formula I- VI may be preferred over the respective free base because such salts impart greater stability or solubility to the molecule thereby facilitating formulation into a dosage form. Accordingly, the invention is further directed to compounds of Formula I- VI, and pharmaceutically acceptable salts thereof.

[00036] Included within the scope of the“compounds of the invention” are all solvates (including hydrates), complexes, polymorphs, prodrugs, radiolabelled derivatives, and stereoisomers of the compounds of Formula I- VI, and salts thereof.

[00037] The compounds of the invention may exist in solid or liquid form. In the solid state, the compounds of the invention may exist in crystalline or non-crystalline form, or as a mixture thereof. For compounds of the invention that are in crystalline form, the skilled artisan will appreciate that pharmaceutically acceptable solvates may be formed wherein solvent molecules are incorporated into the crystalline lattice during crystallization. Solvates may involve non-aqueous solvents such as ethanol, isopropyl alcohol, dimethylsulfoxide (DMSO), acetic acid, ethanolamine, and ethyl acetate, or they may involve water as the solvent that is incorporated into the crystalline lattice. Solvates wherein water is the solvent that is incorporated into the crystalline lattice are typically referred to as “hydrates”. Hydrates include stoichiometric hydrates as well as compositions containing variable amounts of water. The invention includes all such solvates.

[00038] It will be further appreciated that certain compounds of the invention that exist in crystalline form, including the various solvates thereof, may exhibit polymorphism (i.e. the capacity to occur in different crystalline structures). These different crystalline forms are typically known as“polymorphs”. The invention includes such polymorphs. Polymorphs have the same chemical composition but differ in packing, geometrical arrangement, and other descriptive properties of the crystalline solid state. Polymorphs, therefore, may have different physical properties such as shape, density, hardness, deformability, stability, and dissolution properties. Polymorphs typically exhibit different melting points, IR spectra, and X-ray powder diffraction patterns, which may be used for identification. It will be appreciated that different polymorphs may be produced, for example, by changing or adjusting the reaction conditions or reagents, used in making the compound. For example, changes in temperature, pressure, or solvent may result in polymorphs. In addition, one polymorph may spontaneously convert to another polymorph under certain conditions. The term“polymorphs” refers to crystal forms of the same molecule, and different polymorphs may have different physical properties such as, for example, melting temperatures, heats of fusion, solubilities, dissolution rates and/or vibrational spectra as a result of the arrangement or conformation of the molecules in the crystal lattice.

[00039] The term“substituted” in reference to a group indicates that a hydrogen atom attached to a member atom within a group is replaced. It should be understood that the term“substituted” includes the implicit provision that such substitution be in accordance with the permitted valence of the substituted atom and the substituent and that the substitution results in a stable compound (i.e. one that does not spontaneously undergo transformation such as rearrangement, cyclisation, or elimination). In certain embodiments, a single atom may be substituted with more than one substituent as long as such substitution is in accordance with the permitted valence of the atom. Suitable substituents are defined herein for each substituted or optionally substituted group.

[00040] The term“prodrugs” refers to the precursor of the compound of Formula la, and Formula I which on administration undergoes chemical conversion by metabolic processes before becoming active pharmacological substances. In general, such prodrugs will be functional derivatives of a compound of the invention, which are readily convertible in vivo into a compound of the invention.

[00041] The term“alkyl” refers to a saturated hydrocarbon chain having the specified number of carbon atoms. For example, which are not limited, Ci _-6 alkyl refers to an alkyl group having from 1 - 6 carbon atoms, or 1 - 4 carbon atoms. Alkyl groups may be straight or branched chained groups. Representative branched alkyl groups have one, two, or three branches. Preferred alkyl groups include, without limitation, methyl, ethyl, n- propyl, isopropyl, butyl, isobutyl, and /-butyl. [00042] The term“alkoxy” refers to an alkyl group attached via an oxygen linkage to the rest of the molecule. For example, Ci _-6 alkoxy refers to an alkyl group having from 1 - 6 carbon atoms, or 1 - 4 carbon atoms attached via an oxygen linkage to the rest of the molecule. Preferred alkoxy groups include, without limitation, -OCH3 (methoxy), - OC2H5 (ethoxy) and the like.

[00043] The term“haloalkyl” refers to a halogen in an alkyl group as defined above attached via alkyl linkage to the rest of the molecule. For example, Cl -6 haloalkyl refers to an alkyl group having from 1 - 6 carbon atoms, or 1 - 4 carbon atoms wherein one or more hydrogen atoms are replaced by the same number of identical or different halogen atoms. Preferred haloalkyl groups include, without limitation, -CH2C1, -CHC12, trifluoromethyl, 2,2,2-trifluoroethyl, and the like.

[00044] The term“haloalkoxy” refers to a halogen in an alkoxy group as defined above further attached via oxygen linkage to the rest of the molecule. For example, Ci _-6 haloalkoxy refers to an alkoxy group having from 1 - 6 carbon atoms, or 1 - 3 carbon atoms further attached via halo linkage. Preferred haloalkoxy groups include, without limitation, -OCH2CI, -OCHCI2, and the like.

[00045] The term“halo” or“halogen” refers to a halogen radical, for example, fluoro, chloro, bromo, or iodo.

[00046] The term “cycloalkyl” refers to a saturated hydrocarbon ring having a specified number of carbon atoms, which may be monocyclic or polycyclic. For example, which are not limited, C3-10 cycloalkyl refers to a cycloalkyl group having from 3 to 10 member atoms or 3 to 6 member atoms. The polycyclic ring denotes hydrocarbon systems containing two or more ring systems with one or more ring carbon atoms in common i.e. a spiro, fused or bridged structures. For example, which are not limited, C3-6 cycloalkyl refers to a cycloalkyl group having from 3 to 6 membered atoms. Preferred cycloalkyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctanyl, perhydronaphthyl, adamantyl, noradamantyl and norbornyl groups, bridged cyclic groups or spirobicyclic groups e.g spiro [4.4] non-2-yl, and the like.

[00047] The term“aryl” refers to aromatic ring having a specified number of carbon atoms. For example, C5-6 aryl refers to an aryl group having 5 or 6 member atoms, or 6 member atoms. C _6-io aryl refers to an aryl group having 6 to 10 member atoms. Preferred aryl groups include, without limitation, phenyl, and the like.

[00048] The term “heteroaryl” refers to aromatic rings containing from 1 to 3 heteroatoms in the ring.“Heteroaryl” groups may be substituted with one or one or more substituents if so defined herein. The“Ci _-6 heteroaryl” rings having 1 or 6 carbon as member atoms. The term“5-14 membered heteroaryl” has 5 to 14 carbon as member atoms. The“heteroaryl” includes pyridinyl, tetrazolyl and pyrazolyl.“Heteroatom” refers to a nitrogen, sulfur, or oxygen atom, for example a nitrogen atom or an oxygen atom.

[00049] The term“heterocyclic” or refer to saturated or unsaturated monocyclic aliphatic rings containing 5, 6, or 7 ring members including 1-3 heteroatoms or to saturated or unsaturated bicyclic, tricyclic, tetracyclic aliphatic rings containing 5, 6 or 7 ring members including 1-3 heteroatoms, which may include spiro, fused, or bridged ring systems. In certain embodiments, “heterocyclic” groups are saturated. In other embodiments,“heterocyclic” groups are unsaturated “heterocyclic” groups containing more than one heteroatom may contain different heteroatoms“heterocyclic” groups may be substituted with one or more substituents as defined herein “heterocyclic” includes piperidinyl, tetrahydropyranyl, azepinyl, oxazepinyl, azabicyclo[3. l.0]hexanyl.

[00050] The term“heterocycloalkyl-” refers to to a heterocyclic group as defined above further attached via alkyl linkage to the rest of the molecule. For example, 4-10 membered heterocycloalkyl refers to heterocyclic group as defined above further attached via alkyl linkage to the rest of the molecule.

[00051] The phrase “pharmaceutically acceptable” refers to those compounds, materials, compositions, and dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

[00052] As used herein, the term“pharmaceutically acceptable salts” refers to salts that retain the desired biological activity of the subject compound and exhibit minimal undesired toxicological effects. These pharmaceutically acceptable salts may be prepared in situ during the final isolation and purification of the compound, or by separately reacting the purified compound in its free base form with a suitable acid.

[00053] Salts and solvates having non-pharmaceutically acceptable counter- ions or associated solvents are within the scope of the present invention, for example, for use as intermediates in the preparation of other compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, and their pharmaceutically acceptable salts. Thus, one embodiment of the invention embraces compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, and salts thereof. Compounds according to and Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI contain a basic functional group and are therefore capable of forming pharmaceutically acceptable acid addition salts by treatment with a suitable acid. Suitable acids include pharmaceutically acceptable inorganic acids and pharmaceutically acceptable organic acids. Representative pharmaceutically acceptable acid addition salts include hydrochloride, hydrobromide, nitrate, methylnitrate, sulfate, bisulfate, sulfamate, phosphate, acetate, hydroxyacetate, phenyl acetate, propionate, butyrate, iso-butyrate, valerate, maleate, hydroxymaleate, acrylate, fumarate, malate, tartrate, citrate, salicylate, glycollate, lactate, heptanoate, phthalate, oxalate, succinate, benzoate, o- acetoxybenzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, naphthoate, hydroxynaphthoate, mandelate, tannate, formate, stearate, ascorbate, palmitate, oleate, pyruvate, pamoate, malonate, laurate, glutarate, glutamate, estolate, methanesulfonate (mesylate), ethanesulfonate (esylate), 2- hydroxyethanesulfonate, benzenesulfonate (besylate), aminobenzenesulfonate, p- toluenesulfonate (tosylate), and naphthalene-2-sulfonate.

[00054] The term "PD-1/PD-L1 inhibitor or inhibitory compounds" or "inhibitors of PD-1/PD-L1 activation" is used to identify a compound, which is capable of blocking PD-1/PD-L1 pathway to prevent inhibitory signalling from cancer cells and enabling CTLs to elicit an immune response against the target/cancer cells and thus treat cancer and other diseases or conditions associated with activation of PD1/PD-L1.

[00055] The term“cytotoxic agents” or“inhibitors” is used to identify any agents or drugs which are capable of killing cells including cancer cells. These agents or 10 inhibitors may stop cancer cells from growing and dividing and may cause tumors to shrink in size.

[00056] The term“non-cytotoxic agents” or“inhibitors” is used to identify any agents or inhibitors are which does not directly kill cells, but instead affects cellular transport and metabolic functions to ultimately produce cell death.

[00057] The term“immune checkpoint inhibitors agents” or“immune modulators agents” are used to identify any agents or inhibitors that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the“brakes” on the immune system are released 20 and T cells are able to kill cancer cells better. The immune checkpoint inhibitors include inhibitors against immune checkpoint molecules such as CD27, CD28, CD40, CD 122, CD96, CD73, CD47, 0X40, GITR, CSF1R, JAK, PI3K delta, PI3K gamma, TAM, arginase, CD137 (also known as 4-1BB), ICOS, A2AR, B7-H3, B7-H4, BTLA, CTLA- 4, LAG3, TIM3, VISTA, PD-l, PD-L1 and PD-L2. The terms“immune modulators agents” and“immune checkpoint inhibitors” are used interchangeably throughout the present disclosure.

[00058] As discussed in the background section, the identification and development of new PD-1/PD-L1 inhibitor compounds treating cancer and other diseases or conditions associated with activation of PD-1/PD-L1 would open new opportunities in the realm of cancer treatment.

[00059] A term once described, the same meaning applies for it, throughout the disclosure.

[00060] In an embodiment of the present disclosure, there is provided a compound of Formula I

Formula (I)

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein Xi is selected from -CH ₂0-, -OCFh-, -C(0)NH- or - NHC(O)-; R ₄ is selected from hydrogen, hydroxyl, Ci- ₆ alkyl, amino, -C(0)OR _ai, C(0)NRbiRci, C5-6 aryl, or C1-6 heteroaryl, wherein C1-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)OR _ai, C(0)NRbiRd, C5-6 aryl, and C1-6 heteroaryl;R _ai, RM, and R _ci are independently selected from hydrogen or C1-6 alkyl; X is selected from CR3 or N;Ri, R2, R ₃,R ₆, and R ₇ are independently selected from hydrogen, halo, Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci_ ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^d is selected from cyano, amino, Ci _-6 alkyl, Ci _-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)0R ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci _-6 alkyl, Ci-r, haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl- C1-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents;

R ^f is selected from C alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci_ ₄ alkyl, C 1-4 haloalkyl, C ₂-6 alkenyl, C ₂-6 alkynyl, C _6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ⁿ is selected from cyano, halo, C1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C ₂-6 alkenyl, C ₂-6 alkynyl, C 1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R°, or S(0) ₂NR°R°, wherein the C 1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- 10 aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and Ci-4haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2- 4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci- ₆ haloalkyl, Ci _-6 alkyl, Ci- ₆ alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl,

4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C1 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, Ci-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is Ci _-6 alkyl; m is 1 or 2; Ring A is selected from substituted or unsubstituted C5-10 aryl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O; Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

[00061] In an embodiment of the present disclosure, there is provided a compound of Formula I, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein Xi is selected from -CH ₂0-, -OCH ₂-, -C(0)NH- or -NHC(O)-; R4 is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino, - C(0)0Rai, C(0)NRbiRci, C5-6 aryl, or Ci _-6 heteroaryl, wherein Ci _-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NRbiRci, C5-6 aryl, and Ci _-6 heteroaryl; R _ai, R _bi, and R _ci are independently selected from hydrogen or Ci _-6 alkyl; X is CR ₃; Ri, R ₂, R ₃,R ₆, and R ₇ are independently selected from hydrogen, halo, Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C _3-iocycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci_ ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, Ci-4 haloalkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^d is selected from cyano, amino, Ci _-6 alkyl, Ci _-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl- C1-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; R ^f is selected from C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci_ ₄ alkyl, C 1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or

3 R ^p substituents; R ⁿ is selected from cyano, halo, C 1 -4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°,

NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR ⁰S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the C 1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- 10 aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl and C1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^p is selected from halo, cyano, C 1-6 alkyl, C 1-6 haloalkyl, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C2-4 alkenyl, or C2-

4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci- ₆ haloalkyl, Ci _-6 alkyl, Ci- ₆ alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C 1 -4 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, Ci-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is Ci _-6 alkyl; m is 1 or 2; Ring A is selected from substituted or unsubstituted C5-10 aryl; Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

[00062] In an embodiment of the present disclosure, there is provided a compound of Formula II

Formula II

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein Xi is selected from -CH ₂0-, -OCH2-, -C(0)NH- or - NHC(O)-; R ₄ is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C5-6 aryl, or Ci _-6 heteroaryl, wherein Ci _-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NRbiRci, C5-6 aryl, and Ci _-6 heteroaryl; R _al, Rbi, and R _ci are independently selected from hydrogen or Ci _-6 alkyl; R5 is selected from C1-4 alkyl, cyano, or C1-4 haloalkyl; Ri, R ₂, R3,R6, and R ₇ are independently selected from hydrogen, halo, Ci-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)0R ^a, 0C(0)R ^a, 0C(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)0R ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci- ₆alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^cR ^c; wherein the C M alkyl, C ₂-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, Ci _-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci_ ₆ alkyl, Ci_ ₆ haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from C alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the CM alkyl, C 1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°,

S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR ⁰S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the CM alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-io cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)- C1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl and CM haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, CM haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cr,-m aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl- C1-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)0R ^r, 0C(0)R ^r, 0C(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)0R ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2- ₄ alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, C1-6 haloalkyl, C1-6 alkyl, C i-r, alkoxy, C1-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl,

4-6 membered heterocycloalkyl, C _3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C ₁₄ haloalkoxy, wherein the C _1-6 alkyl, C _5-6 aryl, C _3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _5-6 aryl, C _3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is C _1-6 alkyl; Ring B is selected from Cs-io aryl, C _3-6 cycloalkyl, 5-10 membered monocyclic orbicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

[00063] In an embodiment of the present disclosure, there is provided a compound of Formula II, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein Xi is selected from -CH ₂0-, -OCH ₂-, -C(0)NH- or -NHC(O)-; R ₄ is selected from hydrogen, hydroxyl, C _1-6 alkyl, amino, - C(0)ORai, C(0)NRbiRci, C5-6 aryl, or C1-6 heteroaryl, wherein C1-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)OR _ai, C(0)NR _biR _ci, C _5-6 aryl, and C _1-6 heteroaryl; R _ai, R _bi, and R _ci are independently selected from hydrogen or C _1-6 alkyl; R ₅ is selected from C _1-4 alkyl, cyano, or C _1-4 haloalkyl; R ₃ is independently selected from hydrogen, halo, C(0)OR ^a _, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _6-io aryl, or C _3-10 cycloalkyl;Ri, R ₂,R ₆, and R ₇ are independently selected from hydrogen, halo, Ci- 6 alkyl, C _2-6 alkenyl, C2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, NO2, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^cR ^c; wherein the C M alkyl, C ₂-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, Ci _-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)0R ^e, 0C(0)R ^e, 0C(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)0R ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci_ ₆ alkyl, Ci_ ₆ haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C _3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C _1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; R ^c is selected from hydrogen, C _1-6 alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C _1-4 alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from C alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C _1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci_ ₄ alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-ioaryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _{6- 10} aryl-C _1-4 alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)- C _1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents;

NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R°, or S(0) ₂NR°R°, wherein the C 1 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6- io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, C1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and Ci- ₄haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^gis selected from hydrogen, C _1-6 alkyl, Ci- ₄haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C _1-4 alkyl-, C _3-iocycloalkyl-C _1-4 alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ^p is selected from halo, cyano, Ci- ₆ alkyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC (=N CN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C _1-4 alkyl, C _3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C _1-4 haloalkyl, C _2-4 alkenyl, or C _2-4 alkynyl, wherein the Ci- 4 alkyl, C _3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C _2-4 alkenyl, and C _2-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, C _1-6 haloalkyl, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio, C _5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C _3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C _1-4 haloalkoxy, wherein the C _1-6 alkyl, C _5-6 aryl, C _3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _5-6 aryl, C _3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocyclo alkyl; R ⁸ is C _1-6 alkyl; Ring B is selected from C5-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic or bicyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

[00064] In an embodiment of the present disclosure, there is provided a compound of Formula III

Formula III

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein Xi is selected from -CH ₂0-, -OCH ₂-, -C(0)NH- or - NHC(O)-; R ₄ is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C _5-6 aryl, or Ci _-6 heteroaryl; wherein Ci _-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NRbiRci, C5-6 aryl, and Ci _-6 heteroaryl; R _al, Rbi, and R _ci are independently selected from hydrogen or Ci _-6 alkyl; R ₅ is selected from C1-4 alkyl, cyano, or C1-4 haloalkyl; Ri, R ₂, R3,R6, and R ₇ are independently selected from hydrogen, halo, Ci-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)0R ^a, 0C(0)R ^a, 0C(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)0R ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-ioaryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, Ci4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^cR ^c; wherein the C M alkyl, C ₂-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, C1-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci_ ₆ alkyl, Ci_ ₆ haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; ^c is selected from hydrogen, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from C 1 -4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)0R ^g, 0C(0)R ^g, 0C(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)0R ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the CM alkyl, Ci-4haloalkyl, C _2-6 alkenyl, C _2-6alkynyl, C _6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°,

S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R°, or S(0) ₂NR°R°, wherein the CM alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-io cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)- C1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and CM haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, C 1-4 haloalkyl, C ₂-6 alkenyl, C ₂-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci- ₆ haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C M alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS (0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci_ ₆ alkyl, Ci - ₆ haloalkyl, Ci-r, haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, Ci _-6 alkyl, C i-r, alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C1-4 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is Ci- ₆ alkyl.

[00065] In an embodiment of the present disclosure, there is provided a compound of Formula III, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein Xi is selected from -CH ₂0-, -OCH ₂-, or -C(0)NH-; R4 is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino, -C(0)OR _ai, C(0)NRbiRci, C5-6 aryl, or Ci _-6 heteroaryl; wherein Ci _-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)OR _ai, C(0)NRbiRd, C5-6 aryl, and Ci _-6 heteroaryl; R _ai, Rbi, and R _ci are independently selected from hydrogen or Ci _-6 alkyl; R5 is selected from C1-4 alkyl, cyano, or Ci-4 haloalkyl; R3 is independently selected from hydrogen, halo, C(0)OR ^a _, Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, or C3-10 cycloalkyl;Ri, R ₂, R ₆, and R ₇ are independently selected from hydrogen, halo, Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5- 14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci- ₆ alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6- 10 aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2- ₆ alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C ₂-4 alkenyl, C ₂-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, Ci _-6 alkyl, Ci- ₆ haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci_ ₆ alkyl, Ci_ ₆ haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C i- ₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; ^c is selected from hydrogen, Ci _-6 alkyl, C _M haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from C1 -4 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocyclo alkyl) -Ci- ₄ alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the CM alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-ioaryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)- Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, Ci- ₄ alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)-Ci- ₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₄ haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°,

S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR ⁰S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the CM alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-iocycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)- Ci- ₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and C _M haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, C _M haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C ₂-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci- ₆ haloalkyl, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS (0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci_ ₆ alkyl, Ci-6haloalkyl, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents;

R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C _1-4 alkyl, C _3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, Ci- ₄ haloalkyl, C _2-4 alkenyl, or C _2-4 alkynyl, wherein the C _1-4 alkyl, C _3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C _2-4 alkenyl, and C _2-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci-6 haloalkyl, Ci _-6 alkyl, C i-r, alkoxy, Ci _-6 alkylthio, C _5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C _3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C _1-4 haloalkoxy, wherein the Ci _-6 alkyl, C _5-6 aryl, C _3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _5-6 aryl, C _3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is Ci-6 alkyl.

[00066] In an embodiment of the present disclosure, there is provided a compound of Formula IV

Formula IV

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein R5 is selected from C1 alkyl, cyano, or C1-4 haloalkyl; Ri, R ₂, R ₃,R ₆, and R ₇ are independently selected from hydrogen, halo, Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)0R ^a, 0C(0)R ^a, 0C(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)0R ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- 4alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)- C1-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents;

R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- , or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)0R ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the Ci- ₄ alkyl, C _2-4 alkenyl, C _2-4 alkynyl, Ci- ₄ haloalkyl, Ci- ₄ haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents;

R ^c is selected from hydrogen, C1-6 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the C1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from Ci- ₄ alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci _-4 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2- ₆ alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C _1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C _1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, C _1-4 alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered heteroaryl)-Ci-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°,

C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the C _1-4 alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)-Ci- ₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, Ci- ₆haloalkoxy, C _2-6 alkenyl, C _2-6alkynyl and C _1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; ^Rgis selected from hydrogen, Ci- ₆ alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl- C _1-4 alkyl-, C _3-10 cycloalkyl-C _1-4 alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; ^Rp is selected from halo, cyano, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C _1-4 alkyl, C _3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, Ci- ₄haloalkyl, C _2-4 alkenyl, or C _2- ₄ alkynyl, wherein the C _1-4 alkyl, C _3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C _2-4 alkenyl, and C _2-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci- ₆haloalkyl, C _1-6 alkyl, Ci-r, alkoxy, C _1-6 alkylthio, C _5-6 aryl, 5-6 membered heteroaryl,

4-6 membered heterocycloalkyl, C _3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C ₁₄ haloalkoxy, wherein the Ci _-6 alkyl, C _5-6 aryl, C _3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C _1-4 alkoxy, Ci- ₄ haloalkyl, C _1-4 haloalkoxy, C _5-6 aryl, C _3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is C _1-6 alkyl.

In an embodiment of the present disclosure, there is provided a compound of Formula IV, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein R ₅ is selected from C alkyl, cyano, or C _1-4 haloalkyl; R ₃ is independently selected from hydrogen, halo, C(0)0R ^a _, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _6-io aryl, or C _3-10 cycloalkyl;Ri, R ₂, R ₆, and R ₇ are independently selected from hydrogen, halo, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₆ haloalkyl, C _1-6 haloalkoxy, C _6-io aryl, C _3-iocycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, NO ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0)2NR ^aR ^a, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3- _l0 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-14 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, C _1-6 alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, Ci- ₄ alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^cR ^c; wherein the C _M alkyl, C ₂-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, C1-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci_ ₆ alkyl, Ci_ ₆ haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; R ^c is selected from hydrogen, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C 1-4 alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from C i- ₄ alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocyclo alkyl) -C 1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)0R ^g, 0C(0)R ^g, 0C(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)0R ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the CM alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6alkynyl, C _6-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)- Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, Ci- ₄ alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)-Ci- ₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₄ haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°,

S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R°, or S(0) ₂NR°R°, wherein the CM alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-io cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)- CM alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and CM haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, CM haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl- CM alkyl-, C3-io cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C _M alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, Ci-4haloalkyl, C2-4 alkenyl, or C2- 4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C2-4 alkenyl, and C2-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci- ₆haloalkyl, C1-6 alkyl, Ci-r, alkoxy, C1-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl,

4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C1 haloalkoxy, wherein the C1-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, Ci-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is C1-6 alkyl.

[00067] In an embodiment of the present disclosure, there is provided A compound of Formula V

Formula V

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein R ₅ is selected from C alkyl, cyano, or C _1-4 haloalkyl; R ₄ is selected from hydrogen, hydroxyl, C _1-6 alkyl, amino, -C(0)OR _ai, C(0)NR _biR _ci, C _5- ₆ aryl, or C _1-6 heteroaryl; wherein C _1-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)OR _ai, C(0)NR _biR _ci, C _5-6 aryl, and C _1-6 heteroaryl; R _ai, R _bi, and R _ci are independently selected from hydrogen or C _1-6 alkyl; Ri, R ₂, R ₃,R ₆, and R ₇ are independently selected from hydrogen, halo, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _6- ₁₀ aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6- 10 aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered hetero aryl) -C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, NO2, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered heteroaryl)-Ci-4 alkyl-, and (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C ₂-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^cR ^c; wherein the C _M alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)- C1-4 alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, Ci _-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci_ ₆ alkyl, Ci_ ₆ haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-C i- ₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, C _M haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from C1 -4 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocyclo alkyl) -Ci- ₄ alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the CM alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-ioaryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)- Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, Ci- ₄ alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)-Ci- ₄ alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, Ci- ₄ haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°,

3 R ^p substituents; ^p is selected from halo, cyano, Ci _-6 alkyl, Ci- ₆haloalkyl, Ci- ₆haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C2-4 alkenyl, or C2-

4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C1 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is Ci _-6 alkyl.

[00068] In an embodiment of the present disclosure, there is provided a compound of Formula V, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein R5 is selected from C1-4 alkyl, cyano, or C1-4 haloalkyl;R4 is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino; R _ai, Rbi, and Rci are independently selected from hydrogen or C 1-6 alkyl; R3 is independently selected from hydrogen, halo, C(0)OR ^a _, Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, or C3-10 cycloalkyl; Ri, R2, R6, and R ₇are independently selected from hydrogen, halo, Ci _-6 alkyl, C _2-6 alkenyl, C2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0)2R ^a, or S(0)2NR ^aR ^a, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3- io cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3- _l0 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^CS(0) ₂R ^c, NR ^CS(0) ₂NR ^CR ^c, S(0)R ^c, S(0)NR ^CR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, Ci _-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C _3-io cycloalkyl, 4-10 membered heterocycloalkyl, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci _-6 alkyl, C 1-6 haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C _3-io cycloalkyl, or 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 R ^f substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, wherein the C 1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; ^Rf is selected from C1-4 alkyl, C haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)0R ^g, 0C(0)R ^g, 0C(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)0R ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the Ci- ₄ alkyl, Cw haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R°, or S(0) ₂NR°R°, wherein the C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and C 1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; ^Rg is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 R ^p substituents; ^p is selected from halo, cyano, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2 or 3 R ^q substituents ;R ^e, R\ R ^k, R° and R ^r are independently selected from hydrogen, C 1-4 alkyl, C3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, Ci _-6 alkyl, Ci- ₆ alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and Ci- ₄ haloalkoxy, wherein the Ci _-6 alkyl, C _5-6 aryl, C _3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 haloalkyl, C _1-4 haloalkoxy, C _5-6 aryl, C _3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is C _1-6 alkyl.

[00069] In an embodiment of the present disclosure, there is provided a compound of Formula VI

Formula V

their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein R ₅ is selected from C alkyl, cyano, or C _1-4 haloalkyl; R ₄ is selected from hydrogen, hydroxyl, C _1-6 alkyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C _5- ₆ aryl, or C _1-6 heteroaryl; wherein C _1-6 alkyl is optionally substituted with one or more of the groups selected from the group consisting of hydrogen, hydroxyl, amino, -C(0)0R _ai, C(0)NR _biR _ci, C _5-6 aryl, and C _1-6 heteroaryl; R _ai, R _bi, and R _ci are independently selected from hydrogen or C _1-6 alkyl; Ri, R ₂, R ₃,R ₆, and R ₇ are independently selected from hydrogen, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C _6- ₁₀ aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6- 10 aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-14 membered hetero aryl) -C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, CN, NO2, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC(=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-14 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, C _1-6 alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, Ci- ₄ alkyl, C _2-4 alkenyl, C _2-4 alkynyl, Ci- ₄ haloalkyl, Ci- ₄ haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^cS(0) ₂R ^c, NR ^cS(0) ₂NR ^cR ^c, S(0)R ^c, S(0)NR ^cR ^c, S(0) ₂R ^C or S(0) ₂NR ^cR ^c; wherein the C _M alkyl, C _2-4 alkenyl, C _2-4 alkynyl, Ci- ₄ haloalkyl, Ci- ₄ haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)- Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, Ci _-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci_ ₆ alkyl, Ci_ ₆ haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^f substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, or (4-10 membered heterocycloalkyl)-Ci- 4 alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from Ci alkyl, C haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci- ₄ alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocyclo alkyl) -C _1-4 alkyl-, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the CM alkyl, C _1-4 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-ioaryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C _1-4 alkyl-, C _3-10 cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci- ₄ alkyl-, and (4-10 membered heterocycloalkyl)- C _1-4 alkyl- are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, C _1-4 alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-6 membered hetero aryl) -C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci-4 alkyl-, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)OR°, OC(0)R°, OC(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)OR°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°,

S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the CM alkyl, C _3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C _6-io aryl-Ci- ₄ alkyl-, C _3-iocycloalkyl-Ci- ₄ alkyl-, (5-6 membered heteroaryl)- C _1-4 alkyl-, (4-7 membered heterocycloalkyl)-Ci- ₄ alkyl-, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and CM haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^g is selected from hydrogen, Ci _-6 alkyl, CM haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl- C1-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, or (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl-, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C _3-io cycloalkyl-Ci-4 alkyl-, (5-10 membered hetero aryl) -C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci- ₄ alkyl- are optionally substituted with 1, 2, or 3 R ^p substituents; R ^p is selected from halo, cyano, Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C _3-io cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-C _1-4 alkyl-, C _3-io cycloalkyl-Ci- ₄ alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl-, (4-10 membered heterocycloalkyl)-Ci-4 alkyl-, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)0R ^r, 0C(0)R ^r, 0C(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)0R ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the Ci _-6 alkyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C _6-io aryl-Ci-4 alkyl-, C3-10 cycloalkyl-Ci-4 alkyl-, (5-10 membered heteroaryl)-Ci-4 alkyl- and (4-10 membered heterocycloalkyl)-Ci-4 alkyl- are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R ¹, R ^k, R° and R ^r are independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2- 4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, Ci- ₆ haloalkyl, Ci _-6 alkyl, C i-r, alkoxy, Ci _-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl,

4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C1 haloalkoxy, wherein the Ci _-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5- 6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl,

5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is Ci _-6 alkyl.

[00070] In an embodiment of the present disclosure, there is provided a compound of Formula VI, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, wherein R5 is selected from C1-4 alkyl, cyano, or C1-4 haloalkyl;R4 is selected from hydrogen, hydroxyl, Ci _-6 alkyl, amino; R _ai, R _bi, and R _ci are independently selected from hydrogen or C 1-6 alkyl; R3 is independently selected from hydrogen, halo, C(0)OR ^a _, Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, or C3-10 cycloalkyl; Ri, R ₂, R ₆, and R ₇are independently selected from hydrogen, halo, Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, Ci _-6 haloalkyl, Ci _-6 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, N0 ₂, OR ^a, SR ^a, NHOR ^a, C(0)R ^a, C(0)NR ^aR ^a, C(0)OR ^a, OC(0)R ^a, OC(0)NR ^aR ^a, NHR ^a, NR ^aR ^a, NR ^aC(0)R ^a, NR ^aC(0)OR ^a, NR ^aC(0)NR ^aR ^a, C(=NR ^a)R ^a, C(=NR ^a)NR ^aR ^a, NR ^aC (=NR ^a)NR ^aR ^a, NR ^aS(0)R ^a, NR ^aS(0) ₂R ^a, NR ^aS(0) ₂NR ^aR ^a, S(0)R ^a, S(0)NR ^aR ^a, S(0) ₂R ^a, or S(0) ₂NR ^aR ^a, wherein the Ci _-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3- _l0 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, are independently optionally substituted with 1, 2, 3, or 4 R ^b substituents; R ^a is selected from hydrogen, cyano, Ci _-6 alkyl, Ci- ₄ haloalkyl, C _2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein the Ci- ₆ alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl are independently optionally substituted with 1, 2, 3, 4, or 5 R ^d substituents; R ^b is selected from halo, hydroxy, cyano, amino, nitro, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C _3- _l0 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocyclo alkyl, NHOR ^c, OR ^c, SR ^C, C(0)R ^c, C(0)NR ^cR ^c, C(0)OR ^c, OC(0)R ^c, OC(0)NR ^cR ^c, C(=NR ^C)NR ^CR ^C, NR ^CC(=NR ^C)NR ^CR ^C, NHR ^C, NR ^CR ^C, NR ^cC(0)R ^c, NR ^cC(0)OR ^c, NR ^cC(0)NR ^cR ^c, NR ^cS(0)R ^c, NR ^CS(0) ₂R ^c, NR ^CS(0) ₂NR ^CR ^c, S(0)R ^c, S(0)NR ^CR ^c, S(0) ₂R ^C or S(0) ₂NR ^CR ^c; wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 haloalkoxy, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 R ^d substituents; R ^d is selected from cyano, amino, Ci _-6 alkyl, C 1-6 haloalkyl, halo, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, NHOR ^e, OR ^e, SR ^e, C(0)R ^e, C(0)NR ^eR ^e, C(0)OR ^e, OC(0)R ^e, OC(0)NR ^eR ^e, NHR ^e, NR ^eR ^e, NR ^eC(0)R ^e, NR ^eC(0)NR ^eR ^e, NR ^eC(0)OR ^e, C(=NR ^e)NR ^eR ^e, NR ^eC(=NR ^e)NR ^eR ^e, NR ^eC(=NOH)NR ^eR ^e, NR ^eC(=NCN)NR ^eR ^e, S(0)R ^e, S(0)NR ^eR ^e, S(0) ₂R ^e, NR ^eS(0) ₂R ^e, NR ^eS(0) ₂NR ^eR ^e, or S(0) ₂NR ^eR ^e, wherein the Ci _-6 alkyl, C 1-6 haloalkyl, C _6-io aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, or 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 R ^f substituents; R ^c is selected from hydrogen, Ci _-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, wherein the Ci _-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2, 3, 4, or 5 R ^f substituent; R ^f is selected from C1-4 alkyl, C haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, halogen, CN, NHOR ^g, OR ^g, SR ^g, C(0)R ^g, C(0)NR ^gR ^g, C(0)OR ^g, OC(0)R ^g, OC(0)NR ^gR ^g, NHR ^g, NR ^gR ^g, NR ^gC(0)R ^g, NR ^gC(0)NR ^gR ^g, NR ^gC(0)OR ^g, C(=NR ^g)NR ^gR ^g, NR ^gC(=NR ^g)NR ^gR ^g, S(0)R ^g, S(0)NR ^gR ^g, S(0) ₂R ^g, NR ^gS(0) ₂R ^g, NR ^gS(0) ₂NR ^gR ^g, or S(0) ₂NR ^gR ^g; wherein the C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, 3, 4, or 5 R ⁿ substituents; R ⁿ is selected from cyano, halo, C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, Ci- ₆ haloalkoxy, C _2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, R°, NHOR ⁰, OR ⁰, SR°, C(0)R°, C(0)NR°R°, C(0)0R°, 0C(0)R°, 0C(0)NR°R°, NHR°, NR°R°, NR°C(0)R°, NR°C(0)NR°R°, NR°C(0)0R°, C(=NR)NR°R°, NR ⁰C(=NR°)NR°R ⁰, S(0)R°, S(0)NR°R°, S(0) ₂R°, NR°S(0) ₂R°, NR°S(0) ₂NR°R ⁰, or S(0) ₂NR°R°, wherein the C1-4 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C _6-io aryl, 5-6 membered heteroaryl, C1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl and C 1-4 haloalkyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^g is selected from hydrogen, C1-6 alkyl, C haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl wherein the C1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 R ^p substituents; ^p is selected from halo, cyano, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, NHOR ^r, OR ^r, SR ^r, C(0)R ^r, C(0)NR ^rR ^r, C(0)OR ^r, OC(0)R ^r, OC(0)NR ^rR ^r, NHR ^r, NR ^rR ^r, NR ^rC(0)R ^r, NR ^rC(0)NR ^rR ^r, NR ^rC(0)OR ^r, C(=NR ^r)NR ^rR ^r, NR ^rC(=NR ^r)NR ^rR ^r, NR ^rC(=NOH)NR ^rR ^r, NR ^rC(=NCN)NR ^rR ^r, S(0)R ^r, S(0)NR ^rR ^r, S(0) ₂R ^r, NR ^rS(0) ₂R ^r, NR ^rS(0) ₂NR ^rR ^r or S(0) ₂NR ^rR ^r, wherein the C1-6 alkyl, C1-6 haloalkyl, C 1-6 haloalkoxy, C _2-6 alkenyl, C _2-6 alkynyl, C _6-io aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, are optionally substituted with 1, 2 or 3 R ^q substituents; R ^e, R\ R ^k, R° and R ^r are independently selected from hydrogen, C 1-4 alkyl, C3-6 cycloalkyl, C6-io aryl, 5 or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 1-4 haloalkyl, C ₂-4 alkenyl, or C _2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C _6-io aryl, 5 or 6- membered heteroaryl, 4-6 membered heterocycloalkyl, C ₂-4 alkenyl, and C ₂-4 alkynyl are optionally substituted with 1, 2 or 3 R ^q substituents; R ^q is selected from hydroxy, cyano, amino, halo, COOH, C 1-6 haloalkyl, C1-6 alkyl, C i-r, alkoxy, C1-6 alkylthio, C5-6 aryl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR ⁸, NR ⁸R ⁸, and C1-4 haloalkoxy, wherein the C1-6 alkyl, C5-6 aryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with halo, hydroxy, cyano, COOH, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C 1-4 haloalkoxy, C5-6 aryl, C3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl; R ⁸ is C1-6 alkyl

[00071] In an embodiment, the present disclosure relates to compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, or its polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof, which is selected from a group consisting of:

(S)-l-((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4-yl)methyl) piperidine-2-carboxylic acid (1),

N-(2-(((5-methoxy-7 -((2-methyl- [1,1 '-biphenyl] -3 -yl)methoxy) -2,3 -dihydro- lH-inden- 4-yl) methyl)amino)ethyl)acetamide (2),

(S)- l-((7-((3-(l-(3-(3 ,3 -difluoropyrrolidin- 1 -yl)propyl)- 1 H-indol-4-yl)-2- methylbenzyl)oxy)-2,3-dihydro-lH-inden-4-yl)methyl)piperidin e-2-carboxylic acid (3), (S)- 1 -((6-methyl-7-((2-methyl- [1,1 '-biphenyl] -3-yl)methoxy)-2,3-dihydro- 1 H-inden-4- yl)methyl)piperidine-2-carboxylic acid (4),

(S)- 1 -((6-chloro-7-((2-methyl-[ 1 , 1 '-biphenyl] -3-yl)methoxy)-2,3-dihydro- 1 H-inden-4- yl)methyl)piperidine-2-carboxylic acid (5),

Methyl 7-(((2-acetamidoethyl)amino)methyl)-4-((2-methyl-[l,l'-biphe nyl]-3- yl)methoxy)-2, 3-dihydro- lH-indene-5-carboxylate (6),

(S)-l-((7-((3'-(3-(3,3-difluoropyrrolidin-l-yl)propoxy)-2,2' -dimethyl-[l,l'-biphenyl]-3- yl)methoxy)-5-methoxy-2, 3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (7),

(S)-l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl]- 3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (8),

(S)-l-((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[l ,l'-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (9)

N-(2-(((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[l ,l'-biphenyl]-3-yl)methoxy)-

2.3-dihydro- lH-inden-4-yl)methyl)amino)ethyl)acetamide (10)

(S)-5-((5-methoxy-7-((2-methyl-[ l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden- 4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (11)

(S)-l-((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-5-(2,2 ,2-trifluoroethoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidine-2-carboxylic acid (12)

N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-bipheny l]-3-yl)methoxy)-2,3- dihydro- 1 H-inden-4-yl)methyl)amino)ethyl)-N-methylacetamide( 13)

N-(2-(((5-(l-(3-cyanophenyl)ethoxy)-7-((2-methyl-[l,l'-bi phenyl]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)amino)ethyl)acetamide (14)

N-(l-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[l,l'-biphenyl ]-3-yl)methoxy)-2,3- dihydro-lH-inden-4-yl)methyl)piperidin-3-yl)acetamide (15) N-(2-(((7-((2-methyl-[l,l'-biphenyl]-3-yl)methoxy)-2, 3-dihydro- lH-inden-4- yl)methyl) amino)ethyl)acetamide (16)