MACROCYCLIC COMPOUNDS AS STING AGONISTS
FIELD OF THE INVENTION
The present invention relates to macrocyclic compounds having the general Formula (I) and their tautomeric forms, stereoisomers, pharmaceutically acceptable salts, and their combination with suitable medicament, corresponding processes for the synthesis and pharmaceutical compositions and uses of compounds containing the present invention.
CROSS REFERENCE TO THE RELATED APPLICATIONS
The present application claims the benefit of Indian Provisional Patent Application Nos. 201921012258, filed on 28th March 2019 and 201921046194 filed on 13d1 November 2019, the disclosure of which are incorporated herein by reference in their entirety for all purposes.
BACKGROUND OF THE INVENTION
Stimulator of interferon genes (STING, also known as transmembrane protein 173/ TMEM173/MPYS/MITA/ERIS) is a signalling molecule that in humans is encoded by TMEM173 gene. STING is protein with 379 amino acids, consisting of several transmembrane regions. STING protein is expressed in several endothelial and epithelial cell types, as well as in haematopoietic lineage, such as T cells, dendritic cells (DCs) including plasmacytoid dendritic cells (pDCs) and macrophages. STING is associated with endoplasmic reticulum (ER) in the cell and has a major role in controlling the transcription of numerous host defence genes, including type I interferons (IFNs) and pro-inflammatory cytokines.
Recognition of aberrant DNA species or cyclic dinucleotides (CDNs) in the cytosol of the cell leads to the activation of STING. Cytosolic DNA species can activate STING signalling following binding to cyclic GMP-AMP synthase (cGAS). Binding of cytosolic DNA to cGAS

catalyses the production of a type of CDN known as cGAMP (cyclic GMP-AMP), which contains one 2',5'-phosphodiester linkage and a canonical 3',5' linkage (c[G(2',5')pA(3',5')p]). The binding of cGAMP and other bacterial CDNs induce changes in the conformation of STING protein and facilitates the binding of TANK-binding kinase 1 (TBK1). STING-TBK1 complex, further transposes to perinuclear regions of the cell to transport TBK1 to endolysosomal compartments where it phosphorylates the transcription factors like, interferon regulatory factor 3 (IRF3). Similarly, STAT6 and nuclear factor-KB (NF-KB) also get activated downstream to STING activation. These transcription factors then translocate into the nucleus to initiate innate immune gene transcription and production of type IIFN and other cytokines. STING is then rapidly degraded, an event that may avoid problems associated with sustained cytokine production. (Nature Reviews Immunol, 2015, 15, 760-770; Cell Reports, 2015, 11, 1018-1030)
Studies in mice have shown that type I IFN signalling plays an important role in tumour-initiated T cell priming and tumour control (J. Exp. Med. 2011, 208, 1989-2003). Mice lacking the IFN-a/p receptor in DCs failed to reject immunogenic tumours, and CD8a+ DCs from these mice are defective in antigen cross-presentation to CD8+ T cells. Additionally, transcriptional profiling analyses of melanoma patients has publicised that tumours containing infiltrating activated T cells are characterized by a type I IFN transcriptional signature (Cancer Res. 2009, 69, 3077-3085.). Numerous studies have demonstrated that activation of the STING pathway in tumour-resident host APCs is required for induction of a spontaneous CD8+ T cell response against tumour-derived antigens in vivo (Immunity, 2014, 41, 830-842). Extensive evidence directs that the tumour-infiltrating lymphocytes (TILs) are correlated with favourable prediction in diverse malignancies (J. Transl. Med. 2012, 10, 205) and predicts a positive clinical outcome in response to several immunotherapy strategies (Cancer J. 2012, 18, 153— 159). STING activation partially contributing to the antitumor activity of chemotherapeutic agents as well as radiotherapy (Immunity, 2014, 41, 843-852). Further, STING activation and signalling has been discovered to be essential for protection against the development of cancer by promoting antitumor immune responses. Thus, activation of STING represents a potential immunotherapy approach for cancer treatment.

Studies have shown that direct intra-tumoral injection (I.Tu.) of modified CDNs into established B16F10 melanoma, CT26 colon, and 4T1 breast carcinomas resulted in rapid and significant tumour regression and long lasting systemic anti-tumour immunity. So, activation of the STING pathway in the TME by specific agonists might be an effective therapeutic strategy to promote broad tumour-initiated T cell priming and thereby treatment of cancer. (J. Immunol. 2013, 190, 5216-5225; Cell Rep. 2015, 19, 11(7), 1018-30). Besides CDNs, other class of compounds can activate STING.
Parallel to the anticancer mechanism of STING, STING activation to its downstream also leads to induction of several antiviral genes which include IFN-P and several interferons stimulated genes (ISGs). Ablation of STING in murine embryonic fibroblasts made them susceptible to negative-stranded virus infection, including vesicular stomatitis virus. The first-generation mouse STING agonist DMXAA shown to be effective in multiple in-vivo viral models like HBV (hepatitis B virus) DNA Hydrodynamic Mouse Model, Chikungunya virus, H1N1 PR8 influenza strain indicating the utility of STING agonist as antiviral agent against multiple viral infections. (Nature, 2008, 455, 674-678; PLoS Pathog. 2015, 11, 12; Antimicrob. Agents Chemother. 2015, 59, 2 1273-1281; J Leukocyte Bio. 2011, 89, 3 351-357).
International publications WO2017/011920, WO2017/175147, WO2017/175156, WO2018,234805, WO2018,234807, WO2018,234808, WO2019/023635, WO2019/027857, WO2019/027858, and Nature (2018), 564 (7736), 439-443 discloses STING modulators. The compounds of present invention having STING modulator activity are described herein.
SUMMARY OF THE INVENTION
The present invention relates to compounds of general Formula (I), and their tautomeric forms, stereoisomers, pharmaceutically acceptable salts, hydrates, solvates or its prodrug thereof.


wherein,
Gi is independently selected from ring A or j-CH-(CH2)"-ring A;
G2 is -CH=CH-;
ring A is independently selected from optionally substituted heterocyclyl, and optionally substituted heteroaryl;
ring B is aromatic carbocyclic ring;
ringC is optionally substituted five membered heteroaryl;
R1 is -CON(R3)2;
R2 is independently selected from hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C5 monocyclic cycloalkyl;
R3 is independently selected from hydrogen, and optionally substituted C1-C6 alkyl;
m is selected from 0, or 1;
n is selected from 0, 1, or 2;

o is 1;
p is selected from 0, 1, or 2;
when 'alkyF is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, -N(R4)2, and -OR4;
when 'carbocycle' or 'cycloalkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, -N(R4)2, and -OR4;
when 'heterocycle'or 'heterocyclyl' is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=0), halogen, cyano, alkyl, perhaloalkyl, -OR4, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, -P(0)(OR4)R4a, -S02R4a, -SO2NH2, -C(=0)N(H)R4, -C(=0)N(alkyl)R4, -N(H)C(=0)R4a, -N(H)R4, and -N(alkyl)R4;
when the 'heteroaryl' group is substituted, it is substituted with 1 to 4 substituents selected from halogen, cyano, alkyl, perhaloalkyl, -O-alkyl, -O-perhaloalkyl, -N(alkyl)alkyl, -N(H)R4, -S02-alkyl, -N(alkyl)C(=0)alkyl, -N(H)C(=0)alkyl, -C(=0)N(alkyl)alkyl, -C(=0)N(H)alkyl, -C(=0)NH2, -S02N(alkyl)alkyl, -S02N(H)alkyl, -SO2NH2, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, and -P(0)(OR4)R4a;
each R4 is independently selected from hydrogen, alkyl, and cycloalkyl; and
each R4a is independently selected from alkyl, and cycloalkyl.
In another embodiment, the invention provides a compound of general Formula (la), and their tautomeric forms, stereoisomers, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug thereof,


wherein,
R2, ring A, m and n are as defined earlier.
In another embodiment, the invention provides a compound of Formula (lb), and their tautomeric forms, stereoisomers, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug thereof,

wherein,
R2, ring A, and m are as defined earlier.

According to another embodiment, the invention relates the compound of Formula (I), Formula (la) or Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein ring A is optionally substituted heterocyclyl or optionally substituted heteroaryl.
According to another embodiment, the invention relates the compound of Formula (I), and Formula (la) its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein ring A is

According to another embodiment, the invention relates the compound of Formula (lb), and its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein ring A is


According to another embodiment, the invention relates the compound of Formula (I), Formula (la) or Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein R2 is optionally substituted C1-C6 alkyl.
According to another embodiment, the invention relates the compound of Formula (I), Formula (la) or Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein R2 is optionally substituted ethyl.
According to another embodiment, the invention relates the compound of Formula (I), or Formula (la) its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein n is 0,1, or 2.
According to another embodiment, the invention relates the compound of Formula (I), or Formula (la) its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein n is 0.
According to another embodiment, the invention relates the compound of Formula (I), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein R2 is optionally substituted C1-C6 alkyl ; n is 0, 1, or 2; and ring A is optionally substituted heterocyclyl or optionally substituted heteroaryl.
In another embodiment, the invention provides a compound of Formula (I), their tautomeric forms, and their all possible geometrical isomers, including, but not limiting to Formula (A) , Formula (B), Formula (C), Formula (D) , and Formula (E) as represented below:


In another embodiment, the invention provides a compound of Formula (I), Formula (la) or Formula (lb), their tautomeric forms, its pharmaceutically acceptable salt, hydrate, solvate, or its prodrug, wherein the compound is selected from:

Ex. Structure IUPAC Name
No
1 N N O ° (E)-8-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-l,15-bis(l-
X/i^WV ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8,9,16,19-
ft tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-
r )t
o (E)-8-((2S,6R)-2,6-dimethylmorpholino)-l, 15-bis( 1-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 5)

6 N-N\ / U o (S,E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 6)
7 >
o (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(piperidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 7)
8 >
o (E)-8-(azetidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6, lO-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2, 1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 8)
9 O (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-( 1 -methylpiperidin-4-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 9)

10
>
M N O (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
-jCj^rriXm- carboxamido)-8-(piperazin- l-yl)-8,9,16,19-tetrahydro-7H-
r JpO- 6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-

cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
o 10)
11 N N O ° (S,E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-
X^^WU carboxamido)-8-(3-hydroxypyrrolidin-l-yl)-8,9,16,19-
tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-
r )t<^ tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-
0 dicarboxamide (Compound 11)
12 »■ »» o (R,E)-1,15-bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5 -
N \ /? 5 carboxamido)-8-(3-hydroxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-
o tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 12)
13 NO ° (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
X^L/TY-"-, carboxamido)-8-(2-morpholinoethyl)-8,9,16,19-tetrahydro-
;V 7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -
r X^O cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
0 13)

14
J « o (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
carboxamido)-8-((l-methylazetidin-3-yl)methyl)-

8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
0 tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-

dicarboxamide (Compound 14)
15 J »» o (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
N'N\ /? U carboxamido)-8-(( 1 -methylpiperidin-4-yl)methyl)-

8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
0 tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 15)
16 J n O (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
o carboxamido)-8-(morpholinomethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 16)

17
»■ <-. O (E)-15-( 1 -ethyl-3-methyl-1 H-pyrazole-5-carboxamido)-1 -
(l-(2-fluoroethyl)-3-methyl-lH-pyrazole-5-carboxamido)-

8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-
0 2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 17)
18 »■ »» o (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
N~N\ /P U 0 carboxamido)-8-((4-methylpiperazin-l-yl)methyl)-

8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-

dicarboxamide (Compound 18)
19 J n O (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
N'N\ /P U carboxamido)-8-(lH-imidazol-l-yl)-8,9,16,19-tetrahydro-

7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -
0 cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 19)

20
J n 0 (33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-
N'VJ1 N 1 carboxamido)-l lH,61H-2,5-dioxa-l,6(7,1 )-dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-
0 ene-15,65-dicarboxamide (Compound 20)
21 NO ° (33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-
^L^ carboxamido)-31-methyl-llH,61H-2,5-dioxa-1,6(7,1)-

dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-
0 ene-15,65-dicarboxamide (Compound 21)
22 n « O (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
carboxamido)-8-(4-hydroxypiperidin-1 -yl)-8,9,16,19-

tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-
N 0 f O ^/^OH 0 tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 22)
23 NO ° (E)-8-(4-aminopiperidin-1 -yl)-1,15-bis( 1 -ethyl-3-methyl-
XM^W^H, lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-
N-V*1 6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-
J. r\ \ 0 ^/^NH, cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
N-NvA° \ ? ^/ NH2 O 23)

28
> (R,E)-1 -(4,12-dicarbamoyl-1,15 -bis( 1 -ethyl-3-methyl-1H-
N 0 \ ° pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6, lO-

dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2, 1 -cd:8,9,10-c'd']diinden-8-yl)pyrrolidin-3-yl dihydrogen
0 phosphate (Compound 28)
29 J n O (E)-8-(4-cyanopiperidin-l-yl)-l,15-bis(l-ethyl-3-methyl-
N-N 0 J? lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-
0 cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 29)
30 »■ « o (E)-8-(azetidin-3-yl)-1,15-bis( 1 -ethyl-3-methyl-1H-
N"N\ /P U pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6, lO-

dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2, 1 -
0 cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 30)
31 »■ « o (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
N'N\ /? U carboxamido)-8-(piperidin-4-yl)-8,9,16,19-tetrahydro-7H-

6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-
0 cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 3D

32 J « o (E)-1 -(4,12-dicarbamoyl-1,15-bis( 1 -ethyl-3-methyl- 1H-
pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6, lO-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2, 1 -
0 cd:8,9,10-c'd']diinden-8-yl)pyrrolidine-3-carboxylic acid (Compound 32)
33 »■ « o (E)-1 -(4,12-dicarbamoyl-1,15-bis( 1 -ethyl-3-methyl- 1H-
pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6, lO-

dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2, 1 -
r AW
0 cd:8,9,10-c'd']diinden-8-yl)piperidine-4-carboxylic acid (Compound 33)
34 J »> o (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
carboxamido)-8-(l-methylazetidin-3-yl)-8,9,16,19-

tetrahydro-7H-6, lO-dioxa-2,14,15a, 19a-
o tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-

dicarboxamide (Compound 34)

35
NO ° (R,E)-1,15-bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5-
^tf^ carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-
tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-
o tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-

dicarboxamide (Compound 35)
36 > (E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-
N'N O 9 carboxamido)-8-(pyridin-2-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-
(Jfe cd:8,9,10-c'd']diindene-4,12-dicarboxamidexamide

(Compound 36)
0
In a further embodiment, the present invention provides a pharmaceutical composition comprising the compound of Formula (I), Formula (la), Formula (lb) or pharmaceutically acceptable salts thereof and at least one or more pharmaceutically acceptable excipient.
In a further embodiment, the present invention provides a compound of Formula (I), Formula (la), Formula (lb) or pharmaceutically acceptable salts thereof for use in the treatment of a disease or condition in which activation of STING is beneficial.
In a further embodiment, the present invention provides the use of a compound or pharmaceutical composition of Formula (I), Formula (la), Formula (lb) or pharmaceutically acceptable salts thereof in the manufacture of a medicament for the treatment of a disease or condition in which activation of STING is beneficial.

In a further embodiment, the present invention provides a method of treatment of a disease or condition in which activation of STING is beneficial in a subject comprising administering a therapeutically effective amount of a compound of Formula (I), Formula (la), Formula (lb) or its pharmaceutically acceptable salt thereof.
In a further embodiment, the invention provides a method of treatment of disease or condition selected from cancer and infectious diseases, in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula (I), Formula (la), Formula (lb) or its pharmaceutically acceptable salt thereof.
In a further embodiment, the invention provides a method of treatment of cancer such as solid tumors, leukemias and lymphomas.
In a further embodiment, the invention provides a method of treatment of infectious diseases such as viral infection or bacterial infection.
In a further embodiment, the invention provides a composition comprising compound of Formula (I), Formula (la), Formula (lb) or pharmaceutically acceptable salts thereof, and one or more additional therapies.
In a further embodiment, the invention provides a composition comprising compound of Formula (I), Formula (la), Formula (lb) or pharmaceutically acceptable salts thereof, and one or more additional therapies such as chemotherapy, immunotherapy or radiotherapy.
In a further embodiment, the invention provides a vaccine adjuvant comprising a compound of Formula (I), Formula (la), Formula (lb) or pharmaceutically acceptable salts thereof.
In a further embodiment, the invention provides a vaccine composition comprising compound of Formula (I), Formula (la), Formula (lb) or pharmaceutically acceptable salts thereof, and an antigen or antigen composition.

DETAILED DESCRIPTION OF THE INVENTION
General terms used in formula can be defined as follows; however, the meaning stated should not be interpreted as limiting the scope of the term per se.
The term "alkyl" refers to an alkane derived hydrocarbon radical that includes solely carbon and hydrogen atoms in the backbone, contains no unsaturation, has from one to six carbon atoms, and is attached to the remainder of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1- dimethylethyl (t-butyl) and the like. Unless set forth or recited to the contrary, all alkyl groups described or claimed herein may be straight chain or branched, substituted or unsubstituted.
The term 'perhaloalkyl', as used herein, means an alkyl group as defined hereinabove wherein all the hydrogen atoms of the said alkyl group are substituted with halogen. The perhaloalkyl group is exemplified by trifluoromethyl, pentafluoroethyl, and the like.
The term "aromatic ring" as used herein, refers to a monocyclic aromatic hydrocarbon ring system.
The term "heteroaromatic ring" as used herein, refers to a 5-6 membered monocyclic aromatic ring system having 1-2 ring heteroatoms selected from O, N, or S.
The term "cycloalkyl" or 'carbocycle' refers to a non-aromatic mono or multicyclic ring system having 3 to 12 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. Unless set forth or recited to the contrary, all cycloalkyl groups described or claimed herein may be substituted or unsubstituted.
The term " C3-C5 monocyclic cycloalkyl" refers to a substituted or unsubstituted non-aromatic monocyclic ring system having 3 to 5 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, and the like.

The term "aromatic carbocyclic ring", as used herein, refers to aromatic hydrocarbon ring system. Examples include benzene ring, and the like.
The term 'aryl', as used herein, refers to a monovalent monocyclic, bicyclic or tricyclic aromatic hydrocarbon ring system. Examples of aryl groups include phenyl, naphthyl, anthracenyl, fluorenyl, indenyl, azulenyl, and the like.
The term 'heteroaryl', as used herein, refers to a 5-14 membered monocyclic, bicyclic, or tricyclic ring system having 1-4 ring heteroatoms selected from O, N, or S, and the remainder ring atoms being carbon (with appropriate hydrogen atoms unless otherwise indicated), wherein at least one ring in the ring system is aromatic.
The term "heterocycle" or "heterocyclyl", unless otherwise specified, refers to substituted or unsubstituted non-aromatic, monocyclic, bicyclic, tricyclic or bridged/fused/spiro ring system having 3- to 15- membered ring which consists of carbon atoms and with one or more (e.g., 2 or 3) heteroatom(s) independently selected from N, O, S, P(0)(OR4), P(0)(R4a) or S(0)2. The point of attachment may be from any suitable carbon or nitrogen.
The term 'oxo' means a divalent oxygen (=0) attached to the parent group. For example oxo attached to carbon forms a carbonyl, oxo substituted on cyclohexane forms a cyclohexanone, and the like.
The term "tautomer" or "tautomeric form" refers to structural isomers of different energies which are interconvertible via a low energy barrier. For example, proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol isomerizations. Valence tautomers include interconversions by reorganization of some of the bonding electrons.
The term " geometric isomer " refers to E or Z geometric isomers (for example, cis or trans) of double bond.

All tautomeric forms and their possible geometrical isomers, including, but not limiting to Formula (s), Formula (r), and Formula (t), of the formulas and compounds described herein are intended to be encompassed within the scope of the present invention.

The compounds of the present invention may have one or more chiral centers. The absolute stereochemistry at each chiral center may be 'R' or 'S'. The compounds of the invention include all diastereomers and enantiomers and mixtures thereof. Unless specifically mentioned otherwise, reference to one stereoisomer applies to any of the possible stereoisomers. Whenever the stereoisomeric composition is unspecified, it is to be understood that all possible stereoisomers are included.
The term "stereoisomer" refers to a compound made up of the same atoms bonded by the same bonds but having different three-dimensional structures which are not interchangeable. The three-dimensional structures are called configurations. As used herein, the term "enantiomer" refers to two stereoisomers whose molecules are nonsuperimposable mirror images of one another. The term "chiral center" refers to a carbon atom to which four different groups are attached. As used herein, the term "diastereomers" refers to stereoisomers which are not enantiomers. The terms "racemate" or "racemic mixture" refer to a mixture of equal parts of enantiomers.
The term "treating" or "treatment" of a state, disease, disorder, condition or syndrome includes: (a) preventing or delaying the appearance of clinical symptoms of the state, disease, disorder, condition or syndrome developing in a subject that may be afflicted with or predisposed to the state, disease, disorder, condition or syndrome but does not yet experience or display clinical or subclinical symptoms of the state, disease, disorder, condition or

syndrome; (b) inhibiting the state, disease, disorder, condition or syndrome, i.e., arresting or reducing the development of the disease or at least one clinical or subclinical symptom thereof; c) lessening the severity of a disease disorder or condition or at least one of its clinical or subclinical symptoms thereof; and/or (d) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.
The term "subject" includes mammals, preferably humans and other animals, such as domestic animals; e.g., household pets including cats and dogs.
A "therapeutically effective amount" refers to the amount of a compound that, when administered to a subject in need thereof, is sufficient to cause a desired effect. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity, age, weight, physical condition and responsiveness of the subject to be treated.
Compounds disclosed herein and their tautomeric forms, stereoisomers, prodrugs may be prepared, for example, by techniques well known in the organic synthesis and familiar to a practitioner ordinarily skilled in art of this invention. In addition, the processes described herein may enable the synthesis of the compounds of the present invention. However, these may not be the only means by which the compounds described in the invention may be synthesized. Further, the various synthetic steps described herein may be performed in alternate sequences in order to furnish the desired compounds.
In a further aspect, of the present invention, there is provided a compound of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof for use in the treatment of a disease or condition in which activation of STING is beneficial.
In a further aspect of the present invention, there is provided the use of a compound or pharmaceutical composition of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for use in the treatment of a disease or condition in which activation of STING is beneficial.

In a further aspect of the present invention, there is provided a method of the treatment of a disease or condition in which activation of STING is beneficial in a subject comprising administering a therapeutically effective amount of a compound of Formula (I), Formula (la), and Formula (lb), or its pharmaceutically acceptable salt thereof.
In a further aspect the invention provides a method of treatment of disease or condition selected from cancer and infectious diseases, in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula (I), Formula (la), and Formula (lb), or its pharmaceutically acceptable salt thereof.
In a further aspect the invention provides a method of treatment cancer such as solid tumors, leukemias and lymphomas.
In a further aspect the invention provides a method of treatment of infectious diseases such as viral infection or bacterial infection. Examples of solid tumors which may be treated with the compounds of present invention include, but are not limited to, breast cancer, pancreatic cancer, lung cancer, colon cancer, coloretal cancer, brain cancer, renal cancer, testicular cancer, cancer of urethra, rectal cancer, cancer of fallopian tubes, penile cancer, vaginal cancer, stomach cancer, skin cancer, melanoma, liver cancer, gastrointestinal stromal tumors, urothelial cancer, thyroid cancer, parathyroid gland cancer, adrenal cancer, bone cancer, oral cancer, ovarian cancer, uterine cancer, head and neck sqamous cell carcinoma, endometrial cancer, gall bladder cancer, bladder cancer, orophyrangeal cancer, lymph node cancer, glioblastoma, astrocytoma, glioblastoma multiforme or sarcomas of soft tissue, fibrosarcoma, chondrosarcoma, hemangioma, teratoma, lipoma, myxoma, fibroma, rhabdomyoma, teratoma, cholangiocarcinoma, Ewing's sarcoma. Examples of leukemia, which may be treated with the compounds of present invention include, but are not limited to Lymphoblastic T cell leukemia, Chronic myelogenous leukemia, Acute lymphoblastic T cell leukemia, Acute myelobastic leukemia, Hairy-cell leukemia, Chronic neutrophilic leukemia, Mantle cell leukemia, Acute megakaryocytic leukemia, Multiple myeloma, Megakaryoblastic leukemia, Erythroleukemia, Plasmacytoma, Promyelocytic leukemia, Chronic

myelomonocytic leukemia, Myelodysplastic syndrome, Myelofibrosis, Chronic myelogenous leukemia, Polycythemia vera, Thrombocythemia, Chronic lymphocytic leukemia, Prolymphocytic leukemia, Hairy cell leukemia, Waldenstrom's macroglobulinemia, Castleman's disease, Chronic neutrophilic leukemia, Immunoblastic large cell leukemia, Plasmacytoma, and Leukemias in any other parts of body. Examples of lymphoma, which may be treated with the compounds of present invention include, but are not limited to, Hodgkin's disease, non-Hodgkin's lymphoma, Follicular lymphoma, Mantle cell lymphoma, Burkitt's lymphoma, Lymphoblastic T-cell lymphoma, Marginal zone lymphoma, Cutaneous T cell lymphoma, CNS lymphoma, Small lymphocytic lymphoma, Lymphoplasmacytic lymphoma, Diffuse large B-cell lymphoma (DLBCL), Peripheral T-cell lymphoma, Anaplastic large cell lymphoma, Primary mediastinal lymphoma, Mycosis fungoides, Small non-cleaved cell lymphoma, Lymphoblastic lymphoma, Immunoblastic lymphoma, Primary effusion lymphoma and HIV associated (or AIDS related) lymphomas. Examples of viral infection which may be treated with the compounds of present invention include, but are not limited to, human immune deficiency virus (HIV), Human papillomavirus(HPV), hepatitis C virus (HCV), hepatitis B virus (HBV), Influenza (Orthomyxoviridae), Alphavirus, Rotavirus, Sendai, vaccinia, respiratory synctical virus, Lassa virus (Arenaviridae), Rabies virus (Rhabdoviridae), West nile virus, Dengue virus, Japanese encephalitis virus, and other Flaviviridae, RNA virus, DNA virus, virus belonging to the family of Alphaflexiviridae, Astroviridae, Alphatetraviridae, Alvernaviridae, Asfarviridae, Ampullaviridae, Adenoviridae, Ascoviridae, Betaflexiviridae, Bromoviridae, Barnaviridae, Bicaudaviridae. Baculoviridae Closteroviridae, Caliciviridae, Carmotetraviridae, Clavaviridae, Corticoviridae, Dicistroviridae, Endornaviridae, Filoviridae, Globuloviridae, Guttaviridae, Geminiviridae, Hytrosaviridae, Leviviridae, Luteoviridae, Lipothrixviridae, Mesoniviridae, Marnaviridae, Metaviridae, Malacoherpesviridae, Nodaviridae, Nyamiviridae, Nimaviridae, Nanoviridae, Piconaviridae, Partitiviridae, Picobirnaviridae, Paramyxoviridae, Poxviridae, Pandoraviridae, Polymaviridae, Phycodnaviridae, Papillomaviridae, Polydnaviruses, Polymaviridae, Permutotetraviridae, Potyviridae, Retroviridae, Siphoviridae, Sphaerolipoviridae, Virgaviridae, Togaviridae, Turriviridae, Tectiviridae. Examples of bacterial infection which

may be treated with the compounds of present invention include, but are not limited to, infections caused by bacteria belonging to Brucella, Clostridium, Clostrodium, Campylobacter, Enterococcus, Fransicella, Listeria, Legionella, Mycobacteria, Pseudomonas, Salmonella, Staphylococcus, Yersinia genus. In a further aspect, the invention provides a composition comprising compound of Formula (I), Formula (la), and Formula (lb), or its pharmaceutically acceptable salt thereof, and one or more additional therapies.
In a further aspect, the invention provides a composition comprising compound of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof, and one or more additional therapies such as chemotherapy, immunotherapy or radiotherapy.
Chemotherapy comprises administering one or more additional chemotherapeutic agents that may be used in combination with the compounds of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof, chemotherapeutic agents that may be used in combination includes topoisomerase II inhibitors, anti-tumor antibiotics, anti-metabolites, retinoids, antiviral agents, abiraterone acetate, altretamine, anhydrovinblastine, auristatin, bexarotene, bicalutamide, BMS 184476, 2,3,4,5,6- pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, bleomycin, N,N- dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-proly- 1-Lproline-tbutylamide, cachectin, cemadotin, chlorambucil, cyclophosphamide, 3',4'-didehydro-4'deoxy-8'-norvin- caleukoblastine, docetaxol, doxetaxel, cyclophosphamide, carboplatin, carmustine, cisplatin, cryptophycin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, daunorubicin, decitabine dolastatin, doxorubicin (adriamycin), etoposide, 5- fluorouracil, finasteride, flutamide, hydroxyurea and hydroxyureataxanes, ifosfamide, liarozole, lonidamine, lomustine (CCNU), MDV3100, mechlorethamine (nitrogen mustard), melphalan, mivobulin isethionate, rhizoxin, sertenef, streptozocin, mitomycin, methotrexate, taxanes, nilutamide, onapristone, paclitaxel, prednimustine, procarbazine, RPR109881, stramustine phosphate, tamoxifen, tasonermin, taxol, tretinoin, vinblastine, vincristine, vindesine sulfate, and vinflunine.

Immunotherapy comprises administering one or more additional immunostimulatory agents that may be used in combination with the compound of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof. Immunostimulatory agents that may be used in combination herein includes vaccine adjuvants, such as Toll-like receptor agonists, T-cell checkpoint blockers, CTLA4, PD-1, PD-L1, TIM3, OX40, LAG3, B7-H3, GITR, 4-IBB, ICOS, CD40 and KIR antibody. Examples of CTLA-4 and PD-1 antagonists include, but are not limited to, ipilimumab, tremelimumab, nivolumab, pembrolizumab, CT-011, AMP-224, and MDX- 1106.
In a further aspect the invention provides a vaccine adjuvant comprising a compound of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof.
In a further aspect the invention provides a vaccine composition comprising compound of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof, and an antigen or antigen composition.
Antigens and adjuvants that may be used in combination with the compound of Formula (I), Formula (la), and Formula (lb), or a pharmaceutically acceptable salt thereof disclosed herein include B7 costimulatory molecule, interleukin-2, interferon-a, interferon-y, GM-CSF, CTLA-4 antagonists, OX-40 agonist, CD40 agonist, sargramostim, levamisol, vaccinia virus, Bacille Calmette-Guerin (BCG), liposomes, alum, detoxified endotoxins, mineral oils, surface active substances such as lipolecithin, pluronic polyols, polyanions, peptides, and oil or hydrocarbon emulsions. Adjuvants, such as aluminum hydroxide or aluminum phosphate, can be added to increase the ability of the vaccine to trigger, enhance, or prolong an immune response. Additional materials, such as cytokines, chemokines, and bacterial nucleic acid sequences, like CpG, a toll-like receptor (TLR) 9 agonist as well as additional agonists for TLR 2, TLR 4, TLR 5, TLR 7, TLR 8, TLR9, including lipoprotein, LPS, monophosphoryllipid A, lipoteichoic acid, imiquimod, resiquimod, and in addition retinoic acid- inducible gene I (RIG-I) agonists such as poly I:C, used separately or in combination with the described compositions are also potential adjuvants.

The pharmaceutical compositions may be administered by a variety of means including non-parenterally, parenterally, by inhalation spray, topically, or rectally in formulations containing pharmaceutically acceptable carriers, adjuvants and vehicles. Intra-tumoral (directly into the tumor mass) or peri-tumoral (around the tumor mass) administration of the compounds of the present invention.
General Methods of Preparation
The compound of formula described herein may be prepared by techniques known in the art. In addition, the compound of formula described herein may be prepared by following the reaction sequence as depicted in Scheme-1 and Scheme-2. Further, in the following schemes, where specific bases, acids, reagents, solvents, coupling agents, etc., are mentioned, it is understood that other bases, acids, reagents, solvents, coupling agents etc., known in the art may also be used and are therefore included within the scope of the present invention. Variations in reaction conditions, for example, temperature and/or duration of the reaction, which may be used as known in the art, are also within the scope of the present invention. All the isomers of the compound of formula in described in these schemes, unless otherwise specified, are also encompassed within the scope of this invention.
The processes described herein may enable the synthesis of the compounds of the present invention. However, these may not be the only means by which the compounds described in the invention may be synthesized. Further, the various synthetic steps described herein may be performed in alternate sequences to afford the desired compounds.

WE CLAIM:
1. A compound of general Formula (I), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug,

wherein,
Gi is independently selected from ring A or |-CH-(CH2)"-ring A;
G2 is -CH=CH-;
ring A is independently selected from optionally substituted heterocyclyl, and optionally substituted heteroaryl;
ring B is aromatic carbocyclic ring;
ring C is optionally substituted five membered heteroaryl;
R1 is -CON(R3)2;
R2 is independently selected from hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C5 monocyclic cycloalkyl;

R3 is independently selected from hydrogen, and optionally substituted C1-C6 alkyl;
m is selected from 0, or 1;
n is selected from 0, 1, or 2;
o is 1;
p is selected from 0, 1, or 2;
when 'alkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, -N(R4)2, and -OR4;
when 'carbocycle' or 'cycloalkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, -N(R4)2, and -OR4;
when 'heterocycle'or 'heterocyclyl' is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=0), halogen, cyano, alkyl, perhaloalkyl, -OR4, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, -P(0)(OR4)R4a, -S02R4a, -SO2NH2, -C(=0)N(H)R4, -C(=0)N(alkyl)R4, -N(H)C(=0)R4a, -N(H)R4, and -N(alkyl)R4;
when the 'heteroaryl' group is substituted, it is substituted with 1 to 4 substituents selected from halogen, cyano, alkyl, perhaloalkyl, -O-alkyl, -O-perhaloalkyl, N(alkyl)alkyl, -N(H)R4, -S02-alkyl, -N(alkyl)C(=0)alkyl, -N(H)C(=0)alkyl, -C(=0)N(alkyl)alkyl, -C(=0)N(H)alkyl, -C(=0)NH2, -S02N(alkyl)alkyl, -S02N(H)alkyl, -SO2NH2, -C(=0)OH, -OP(0)(OR4)2, -P(0)(0R4)2, and -P(0)(OR4)R4a;
each R4 is independently selected from hydrogen, alkyl, and cycloalkyl; and
each R4a is independently selected from alkyl, and cycloalkyl.
2. A compound of Formula (la), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug,


wherein,
R2 is independently selected from hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C5 monocyclic cycloalkyl;
ring A is independently selected from optionally substituted heterocyclyl, and optionally substituted heteroaryl;
m is selected from 0, or 1;
n is selected from 0, 1, or 2;
when 'alkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, -N(R4)2, and -OR4;
when 'carbocycle' or 'cycloalkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, -N(R4)2, and -OR4;
when 'heterocycle'or 'heterocyclyl' is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=0), halogen, cyano, alkyl, perhaloalkyl, -OR4, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, -P(0)(OR4)R4a, -S02R4a, -SO2NH2, -C(=0)N(H)R4, -C(=0)N(alkyl)R4, -N(H)C(=0)R4a, -N(H)R4, and -N(alkyl)R4;

when the 'heteroaryl' group is substituted, it is substituted with 1 to 4 substituents selected from halogen, cyano, alkyl, perhaloalkyl, -O-alkyl, -O-perhaloalkyl, N(alkyl)alkyl, -N(H)R4, -S02-alkyl, -N(alkyl)C(=0)alkyl, -N(H)C(=0)alkyl, -C(=0)N(alkyl)alkyl, -C(=0)N(H)alkyl, -C(=0)NH2, -S02N(alkyl)alkyl, -S02N(H)alkyl, -S02NH2, -C(=0)OH, -OP(0)(OR4)2, -P(0)(0R4)2, and -P(0)(OR4)R4a;
each R4 is independently selected from hydrogen, alkyl, and cycloalkyl; and
each R4a is independently selected from alkyl, and cycloalkyl.
3. A compound of Formula (lb), its tautomeric form, its stereoisomer, its
pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug,

wherein,
R2 is independently selected from hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C5 monocyclic cycloalkyl;
ring A is independently selected from optionally substituted heterocyclyl, and optionally substituted heteroaryl;

m is selected from 0, or 1;
when 'alkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, -N(R4)2, and -OR4;
when 'carbocycle' or 'cycloalkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, -N(R4)2, and -OR4;
when 'heterocycle'or 'heterocyclyl' is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=0), halogen, cyano, alkyl, perhaloalkyl, -OR4, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, -P(0)(OR4)R4a, -S02R4a, -SO2NH2, -C(=0)N(H)R4, -C(=0)N(alkyl)R4, -N(H)C(=0)R4a, -N(H)R4, and -N(alkyl)R4;
when the 'heteroaryl' group is substituted, it is substituted with 1 to 4 substituents selected from halogen, cyano, alkyl, perhaloalkyl, -O-alkyl, -O-perhaloalkyl, N(alkyl)alkyl, -N(H)R4, -S02-alkyl, -N(alkyl)C(=0)alkyl, -N(H)C(=0)alkyl, -C(=0)N(alkyl)alkyl, -C(=0)N(H)alkyl, -C(=0)NH2, -S02N(alkyl)alkyl, -S02N(H)alkyl, -SO2NH2, -C(=0)OH, -OP(0)(OR4)2, -P(0)(0R4)2, and -P(0)(OR4)R4a;
each R4 is independently selected from hydrogen, alkyl, and cycloalkyl; and
each R4a is independently selected from alkyl, and cycloalkyl.
4. The compound of Formula (I), Formula (la), Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug, as claimed in claim 1, 2 and 3, wherein, ring A is optionally substituted heterocyclyl or optionally substituted heteroaryl.
5. The compound of Formula (I), Formula (la), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug, as claimed in claim 1 and 2, wherein, ring A is


6. The compound of Formula (I), Formula (la), Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug, as claimed in claim 1, 2 and 3, wherein, R2 is ethyl.
7. The compound of Formula (I), Formula (la), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug, as claimed in claim 1 and 2, wherein, n is 0.
8. The compound of Formula (I), Formula (la), Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug, as claimed in claim 1 and 2, wherein, R2 is Ci-C6 alkyl ; n is 0, 1, or 2; and ring A is optionally substituted heterocyclyl or optionally substituted heteroaryl.
9. The compound of Formula (I), Formula (la), Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug, as claimed in claim 1 to 8, wherein, the compound is selected from:
(E)-8-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
i);

(E)-8-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
2);
(E)-1,15-bis( 1-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd: 8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 3);
(E)-8-(4,4-difluoropiperidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
4);
(E)-8-((2S,6R)-2,6-dimethylmorpholino)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
5);
(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 6);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(piperidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 7);
(E)-8-(azetidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 8);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( l-methylpiperidin-4-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 9);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(piperazin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 10);

(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
ID;
(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 12);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(2-morpholinoethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 13);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(( 1 -methylazetidin-3-yl)methyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 14);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(( l-methylpiperidin-4-yl)methyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 15);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(morpholinomethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 16);
(E)-15-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-l-(l-(2-fluoroethyl)-3-methyl- lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd: 8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 17);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-((4-methylpiperazin-1 -yl)methyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 18);

(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( lH-imidazol-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 19);
(33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-llH,61H-2,5-dioxa-1,6(7, l)-dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-ene-15,65-dicarboxamide (Compound 20);
(33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-31-methyl-HH,61H-2,5-dioxa-1,6(7,1 )-dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-ene-15,65-dicarboxamide (Compound 21);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(4-hydroxypiperidin-1-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 22);
(E)-8-(4-aminopiperidin-1 -yl)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
23);
(S,E)-l-(4,12-dicarbamoyl-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)pyrrolidin-3-yl dihydrogen phosphate (Compound 24);
(E)-1 -(4,12-dicarbamoyl-1,15 -bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)piperidin-4-yl dihydrogen phosphate (Compound 25);
(E)-8-(3-cyanopyrrolidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 26);
(E)-8-(3-aminopyrrolidin-1 -yl)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
27);

(R,E)-l-(4,12-dicarbamoyl-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)pyrrolidin-3-yl dihydrogen phosphate (Compound 28);
(E)-8-(4-cyanopiperidin-1 -yl)-1,15-bis( 1 -ethyl-3-methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 29);
(E)-8-(azetidin-3-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 30);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(piperidin-4-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 31);
(E)-1 -(4,12-dicarbamoyl-1,15 -bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)pyrrolidine-3-carboxylic acid (Compound 32);
(E)-1 -(4,12-dicarbamoyl-1,15 -bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)piperidine-4-carboxylic acid (Compound 33);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( 1 -methylazetidin-3-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 34);
(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 35); and
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(pyridin-2-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamidexamide (Compound 36).

10. The compound of Formula (I), Formula (la), Formula (lb), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, its solvate or its prodrug, as claimed in claim 1 to 8, wherein, the compound is selected from:
(E)-8-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
i);
(E)-8-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
2);
(E)-1,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd: 8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 3);
(E)-8-(4,4-difluoropiperidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
4);
(E)-8-((2S,6R)-2,6-dimethylmorpholino)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
5);
(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 6);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( l-methylpiperidin-4-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 9);
(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-

tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
ID;
(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 12);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(2-morpholinoethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 13);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(morpholinomethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 16);
(E)-15-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-l-(l-(2-fluoroethyl)-3-methyl- lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 17);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( lH-imidazol-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 19) ;
(33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-llH,61H-2,5-dioxa-1,6(7, l)-dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-ene-15,65-dicarboxamide (Compound 20);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(4-hydroxypiperidin-1-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 22);
(E)-8-(3-cyanopyrrolidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 26);
(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 35); and

(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(pyridin-2-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamidexamide (Compound 36).
11. A compound of general Formula (I) and its pharmaceutical^ acceptable salt

wherein,
Gi is independently selected from ring A or j-CH-(CH2)"-ring A;
G2 is -CH=CH-;
ring A is independently selected from optionally substituted heterocyclyl, and optionally substituted heteroaryl;
ring B is aromatic carbocyclic ring;
ring C is optionally substituted five membered heteroaryl;
R1 is -CON(R3)2;
R2 is independently selected from hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C5 monocyclic cycloalkyl;

R3 is independently selected from hydrogen, and optionally substituted C1-C6 alkyl;
m is selected from 0, or 1;
n is selected from 0, 1, or 2;
o is 1;
p is selected from 0, 1, or 2;
when 'alkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, -N(R4)2, and -OR4;
when 'carbocycle' or 'cycloalkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, -N(R4)2, and -OR4;
when 'heterocycle'or 'heterocyclyl' is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=0), halogen, cyano, alkyl, perhaloalkyl, -OR4, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, -P(0)(OR4)R4a, -S02R4a, -SO2NH2, -C(=0)N(H)R4, -C(=0)N(alkyl)R4, -N(H)C(=0)R4a, -N(H)R4, and -N(alkyl)R4;
when the 'heteroaryl' group is substituted, it is substituted with 1 to 4 substituents selected from halogen, cyano, alkyl, perhaloalkyl, -O-alkyl, -O-perhaloalkyl, N(alkyl)alkyl, -N(H)R4, -S02-alkyl, -N(alkyl)C(=0)alkyl, -N(H)C(=0)alkyl, -C(=0)N(alkyl)alkyl, -C(=0)N(H)alkyl, -C(=0)NH2, -S02N(alkyl)alkyl, -S02N(H)alkyl, -SO2NH2, -C(=0)OH, -OP(0)(OR4)2, -P(0)(0R4)2, and -P(0)(OR4)R4a;
each R4 is independently selected from hydrogen, alkyl, and cycloalkyl; and
each R4a is independently selected from alkyl, and cycloalkyl.
12. A compound of Formula (la) and its pharmaceutically acceptable salt,


wherein,
R2 is independently selected from hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C5 monocyclic cycloalkyl;
ring A is independently selected from optionally substituted heterocyclyl, and optionally substituted heteroaryl;
m is selected from 0, or 1;
n is selected from 0, 1, or 2;
when 'alkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, -N(R4)2, and -OR4;
when 'carbocycle' or 'cycloalkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, -N(R4)2, and -OR4;
when 'heterocycle'or 'heterocyclyl' is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=0), halogen, cyano, alkyl, perhaloalkyl, -OR4, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, -P(0)(OR4)R4a, -S02R4a, -SO2NH2, -C(=0)N(H)R4, -C(=0)N(alkyl)R4, -N(H)C(=0)R4a, -N(H)R4, and -N(alkyl)R4;

when the 'heteroaryl' group is substituted, it is substituted with 1 to 4 substituents selected from halogen, cyano, alkyl, perhaloalkyl, -O-alkyl, -O-perhaloalkyl, N(alkyl)alkyl, -N(H)R4, -S02-alkyl, -N(alkyl)C(=0)alkyl, -N(H)C(=0)alkyl, -C(=0)N(alkyl)alkyl, -C(=0)N(H)alkyl, -C(=0)NH2, -S02N(alkyl)alkyl, -S02N(H)alkyl, -S02NH2, -C(=0)OH, -OP(0)(OR4)2, -P(0)(0R4)2, and -P(0)(OR4)R4a;
each R4 is independently selected from hydrogen, alkyl, and cycloalkyl; and
each R4a is independently selected from alkyl, and cycloalkyl.
13. A compound of Formula (lb) and its pharmaceutically acceptable salt,

wherein,
R2 is independently selected from hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C5 monocyclic cycloalkyl;
ring A is independently selected from optionally substituted heterocyclyl, and optionally substituted heteroaryl;
m is selected from 0, or 1;

when 'alkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, -N(R4)2, and -OR4;
when 'carbocycle' or 'cycloalkyl' is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, alkyl, perhaloalkyl, -N(R4)2, and -OR4;
when 'heterocycle'or 'heterocyclyl' is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=0), halogen, cyano, alkyl, perhaloalkyl, -OR4, -C(=0)OH, -OP(0)(OR4)2, -P(0)(OR4)2, -P(0)(OR4)R4a, -S02R4a, -SO2NH2, -C(=0)N(H)R4, -C(=0)N(alkyl)R4, -N(H)C(=0)R4a, -N(H)R4, and -N(alkyl)R4;
when the 'heteroaryl' group is substituted, it is substituted with 1 to 4 substituents selected from halogen, cyano, alkyl, perhaloalkyl, -O-alkyl, -O-perhaloalkyl, N(alkyl)alkyl, -N(H)R4, -S02-alkyl, -N(alkyl)C(=0)alkyl, -N(H)C(=0)alkyl, -C(=0)N(alkyl)alkyl, -C(=0)N(H)alkyl, -C(=0)NH2, -S02N(alkyl)alkyl, -S02N(H)alkyl, -SO2NH2, -C(=0)0H, -OP(0)(OR4)2, -P(0)(OR4)2, and -P(0)(OR4)R4a;
each R4 is independently selected from hydrogen, alkyl, and cycloalkyl; and
each R4a is independently selected from alkyl, and cycloalkyl.
14. The compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 11, 12 and 13, wherein ring A is optionally substituted heterocyclyl or optionally substituted heteroaryl.
15. The compound of Formula (I), Formula (la), or its pharmaceutically acceptable salt as claimed in claim 11 and 12, wherein, ring A is selected from


16. The compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 11, 12 and 13, wherein, R2 is ethyl.
17. The compound of Formula (I), Formula (la), or its pharmaceutically acceptable salt as claimed in claim 11 and 12, wherein, n is 0.
18. The compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 11 and 12, wherein, R2 is Ci-C6 alkyl; n is 0, 1, or 2; and ring A is optionally substituted heterocyclyl or optionally substituted heteroaryl.
19. The compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 11 to 18, wherein the compound is selected from:
(E)-8-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
i);
(E)-8-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
2);

(E)-1,15-bis( 1-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd: 8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 3);
(E)-8-(4,4-difluoropiperidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
4);
(E)-8-((2S,6R)-2,6-dimethylmorpholino)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
5);
(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 6);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(piperidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 7);
(E)-8-(azetidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 8);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( l-methylpiperidin-4-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 9);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(piperazin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 10);
(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
ID;

(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 12);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(2-morpholinoethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 13);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(( 1 -methylazetidin-3-yl)methyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 14);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(( l-methylpiperidin-4-yl)methyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 15);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(morpholinomethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 16);
(E)-15-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-l-(l-(2-fluoroethyl)-3-methyl- lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 17);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-((4-methylpiperazin-1 -yl)methyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-
tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 18);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( lH-imidazol-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 19);
(33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-llH,61H-2,5-dioxa-1,6(7, l)-dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-ene-15,65-dicarboxamide (Compound 20);

(33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-31-methyl-HH,61H-2,5-dioxa-l,6(7,l)-dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-ene-15,65-dicarboxamide (Compound 21);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(4-hydroxypiperidin-1-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 22);
(E)-8-(4-aminopiperidin-1 -yl)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
23);
(S,E)-l-(4,12-dicarbamoyl-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)pyrrolidin-3-yl dihydrogen phosphate (Compound 24);
(E)-1 -(4,12-dicarbamoyl-1,15 -bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)piperidin-4-yl dihydrogen phosphate (Compound 25);
(E)-8-(3-cyanopyrrolidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 26);
(E)-8-(3-aminopyrrolidin-1 -yl)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
27);
(R,E)-l-(4,12-dicarbamoyl-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)pyrrolidin-3-yl dihydrogen phosphate (Compound 28);
(E)-8-(4-cyanopiperidin-1 -yl)-1,15-bis( 1 -ethyl-3-methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 29);

(E)-8-(azetidin-3-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 30);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(piperidin-4-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 31);
(E)-1 -(4,12-dicarbamoyl-1,15 -bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)pyrrolidine-3-carboxylic acid (Compound 32);
(E)-1 -(4,12-dicarbamoyl-1,15 -bis( 1 -ethyl-3 -methyl-1 H-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diinden-8-yl)piperidine-4-carboxylic acid (Compound 33);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( 1 -methylazetidin-3-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 34);
(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 35); and
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(pyridin-2-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamidexamide (Compound 36).
20. The compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 11 to 18, wherein the compound is selected from:
(E)-8-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
i);
(E)-8-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-

tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
2);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd: 8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 3);
(E)-8-(4,4-difluoropiperidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
4);
(E)-8-((2S,6R)-2,6-dimethylmorpholino)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
5);
(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 6);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( l-methylpiperidin-4-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 9);
(S,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound
ID;
(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-hydroxypyrrolidin-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 12);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(2-morpholinoethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 13);

(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(morpholinomethyl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 16);
(E)-15-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-l-(l-(2-fluoroethyl)-3-methyl- lH-pyrazole-5-carboxamido)-8-morpholino-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 17);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-( lH-imidazol-1 -yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 19) ;
(33R,35R,E)-12,62-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-llH,61H-2,5-dioxa-1,6(7, l)-dibenzo[d]imidazola-3(3,5)-pyrrolidinacyclodecaphan-8-ene-15,65-dicarboxamide (Compound 20);
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(4-hydroxypiperidin-1-yl)-8,9,16,l 9-tetrahydro-7H-6,10-dioxa-2,14,15 a, 19a-tetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 22);
(E)-8-(3-cyanopyrrolidin-l-yl)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 26);
(R,E)-l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8-(3-methoxypyrrolidin-l-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a,19a-tetraazacyclopentadeca[3,2,l-cd:8,9,10-c'd']diindene-4,12-dicarboxamide (Compound 35); and
(E)-1,15-bis( 1 -ethyl-3-methyl- lH-pyrazole-5-carboxamido)-8-(pyridin-2-yl)-8,9,16,19-tetrahydro-7H-6,10-dioxa-2,14,15a, 19a-tetraazacyclopentadeca[3,2,1 -cd:8,9,10-c'd']diindene-4,12-dicarboxamidexamide (Compound 36).
21. A pharmaceutical composition comprising the compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 1 to 20 and at least one or more pharmaceutically acceptable excipient.

22. Use of the compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 1-20 for the manufacture of a medicament for the treatment of a disease or condition in which activation of STING is beneficial.
23. A method of treating a disease or condition in which activation of STING is beneficial in a subject comprising administering a therapeutically effective amount of the compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 1 -20.
24. The method according to claim 23, wherein the disease or disorder is cancer or infectious diseases.
25. The method according to claim 23, wherein the disease or disorder is cancer such as solid tumor, leukemia and lymphoma.
26. The method according to claim 23, wherein the disease or disorder is infectious diseases such as viral infection or bacterial infection.
27. The method according to claim 25, wherein the disease or disorder is selected from brain cancer, renal cancer, testicular cancer, cancer of urethra, rectal cancer, cancer of fallopian tubes, penile cancer, vaginal cancer, stomach cancer, skin cancer, liver cancer, gastrointestinal stromal tumors, urothelial cancer, thyroid cancer, parathyroid gland cancer, adrenal cancer, bone cancer, oral cancer, ovarian cancer, uterine cancer, head and neck sqamous cell carcinoma, endometrial cancer, gall bladder cancer, renal cancer, bladder cancer, orophyrangeal cancer, lymph node cancer, gliobalstoma, astrocytoma, glioblastoma multiforme or sarcomas of soft tissue, fibrosarcoma, chondrosarcoma, hemangioma, teratoma, lipoma, myxoma, fibroma, rhabdomyoma, teratoma, cholangiocarcinoma, myeloma, Ewing's sarcoma, myeloma, Hodgkin's disease, non-Hodgkin's lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt's lymphoma, lymphoblastic T-cell lymphoma, marginal zone lymphoma, cutaneous T cell lymphoma, CNS lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, diffuse large cell lymphoma (DLBCL), peripheral T-cell lymphoma, anaplastic large cell lymphoma, primary mediastinal lymphoma, mycosis fungoides, small non- cleaved cell lymphoma, lymphoblastic lymphoma, immunoblastic lymphoma, primary effusion

lymphoma, HIV associated (or AIDS related) lymphomas, lymphoblastic T cell leukemia, chronic myelogenous leukemia, acute lymphoblastic T cell leukemia, lymphoblastic T cell leukemia, acute myelobastic leukemia, hairy-cell leukemia, chronic neutrophilic leukemia, mantle cell leukemia, acute megakaryocyte leukemia, multiple myeloma, megakaryoblastic leukemia, erythroleukemia, plasmacytoma, promyelocytic leukemia, chronic myelomonocytic leukemia, myelodysplastic syndrome, myelofibrosis, chronic myelogenous leukemia, polycythemia vera, thrombocythemia, chronic lymphocytic leukemia, prolymphocytic leukemia, hairy cell leukemia, Waldenstrom's macroglobulinemia, Castleman's disease, chronic neutrophilic leukemia, immunoblastic large cell leukemia and plasmacytoma.
28. The method according to claim 26, wherein the disease or disorder is selected from HIV, HPV, HCV, HBV, alphavirus, rotavirus or influenza infection.
29. A method according to claim 27 and 28 further involving one or more additional therapy.
30. A method according to claim 29 wherein, the additional therapy is selected from chemotherapy, immunotherapy or radiotherapy.
31. The compound of Formula (I), Formula (la), Formula (lb), or its pharmaceutically acceptable salt as claimed in claim 1 to 20, for use as a vaccine adjuvant.
32. A composition comprising a compound of Formula (I), Formula (la), Formula (lb) or its pharmaceutically acceptable salt as claimed in claim 1 to 20 and an antigen or antigen composition.