NOVEL SUBSTITUTED SULFONYLUREA AND SULFOXIMINEUREA DERIVATIVES

FIELD OF THE INVENTION

The present invention relates to novel compounds of the general formula (I) their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers and polymorphs. The invention also relates to processes for the preparation of the compounds of invention, pharmaceutical compositions containing the compounds and their use as the compounds of the invention belong to the family of NOD-like receptor family (NLR) protein NLRP3 modulators. The present invention thus relates to novel NLRP3 modulators as well as to the use of the novel inhibitor compounds in the treatment of diseases or conditions in which interleukin 1b activity is implicated.

BACKGROUND OF THE INVENTION

The NOD-like receptor family (NLR) protein NLRP3 is an intracellular signaling molecule that senses many pathogens, environmental and host-derived factors. (Wen., et. al., Immunity. 2013; 39:432-441). Activation of NLRP3 leads to binding with apoptosis associated speck-like protein containing a CARD (ASC). ASC in turn interacts with the cysteine protease caspase-1, forming a complex termed the inflammasome. This results in the activation of caspase-1, which cleaves the pro-inflammatory cytokines IL-Ib and IL-18 to their active forms and mediates a type of inflammatory cell death known as pyroptosis. Other intracellular pattern recognition receptors (PRRs) are also capable of forming inflammasomes. These include other NLR family members such as NLRP1 and NLRC4 and non-NLR PRRs such as the double-stranded DNA (dsDNA) sensors absent in melanoma 2 (AIM2) and interferon, gamma inducible protein 16 (IFI16) (Latz, et. ah, Nat Rev Immunol.

2013; 13:397-411). NLRP3 -dependent IL-Ib processing can also be activated by an indirect, non-canonical pathway downstream of caspase-1 (Lamkanfi, et. al., Cell. 2014; 157:1013-1022).

Inflammasome components such as NLRP3, ASC and caspase-1 are expressed in immune cells in the liver including Kupffer cells, infiltrating macrophages, hepatocytes, and hepatic stellate cells. Inflammasome activation is dependent on two successive signals. Signal 1 is driven by TLR and IL-1R signaling, includes expression of component proteins including NLRP3, ASC, pro-caspase-1, pro-IL-Ib, and pro-IL-18. Signal 2 is provided by danger

signals (DAMPS) that during NASH development are mainly released by stressed or dying hepatocytes or via a ”leaky” gut (PAMPs). This process leads to oligomerization of the inflammasome components and cleavage of pro-caspase‐1, leading to the release of active pro-inflammatory cytokines.

The NLRP3 inflammasome acts as a key mediator of inflammatory responses through the activation of caspase-1 leading to processing and release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). The NLRP3 inflammasome is a component of the inflammatory process and its aberrant activation is pathogenic in inherited disorders such as the rare periodic fever syndrome, cryopyrin associated periodic syndromes (CAPS), Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, atherosclerosis, asthma, gouty arthritis, and inflammatory central nervous system (CNS) diseases including Alzheimer’s and other brain diseases. (Masters, et. al., Annu Rev Immunol. 2009; 27:621–668; Strowig, et. al., Nature 2012, 481, 278−286; Guo, et. al., Nat. Med. 2015, 21, 677; Ising, et.al., Nature 2019, 575, 669–673)

Inflammation is an essential host response to infection and injury. The regulation of the pro-inflammatory cytokine interleukin-1β (IL-1β), which is central to host responses to infection, also causes tissue injury when activated inappropriately. (Dinarello, et. al., Nat. Rev. Drug Discovery 2012, 11, 633−652.) NLRP3 inflammasome activation plays a key role in each of the components including induction of pro-inflammatory signaling, hepatocellular injury and cell death, and activation of the hepatic stellate cells (HSC) that are responsible for collagen deposition and liver fibrosis. In particular, the transition from NAFLD to NASH associates with NLRP3-inflammasome activation and an increased expression of inflammasome-related components, including apoptosis-associated speck-like protein containing a carboxy-terminal CARD (ASC), caspase-1 (CASP-1) and pannexin. (Mridha, et. al., Journal of Hepatology, 2017, 66 (5), 1037-1046)

Current treatments for NLRP3 related diseases include biologic agents that target IL-1. These are the recombinant IL-1 receptor antagonist Anakinra, the neutralizing IL-1β antibody Canakinumab and the soluble decoy IL-1 receptor Rilonacept.

Suppression of IL-Ib and IL-18 using NLRP3 inflammasome inhibitors would be an effective therapy during a cytokine storm and might be a plausible treatment option for diseases like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Spanish flu, COVID19 (Coronavirus disease 2019), hepatitis C virus, chikungunya virus, influenza A virus, herpes simplex virus type 1 and Japanese encephalitis vims, where high levels of interleukin (IE)- 1 b and/or IL-18 have been associated with inflammation and Pathogenesis (. Lancet 2020, 395, (10223), 497-506; The FASEB Journal 2020, 33, 8865-6677).

Wipo patent application No. W098/32733, W02001/019390, W02014/190015,

WO2016/123229 W02016/131098 disclosed sulfonylureas derivatives and related compounds as NLRP3 inflammasome inhibitors. WO2017/017469 disclosed certain cyclic diarylboron derivatives as NLRP3 inflammasome inhibitors for the treatment of diseases or conditions in which interleukin 1b activity is implicated. Some of the recent patent applications such as W02017/031161, WO2017/079352, WO2017/129897,

WO2017/184623, WO2018/225018, W02019/043610, WO2019/023147, WO2019/068772, W02020/035466, W02020/208249 W02020/035465, WO2020/254697 also disclosed certain class of compounds as NLRP3 inhibitors.

We herein disclose novel compounds of general formula (I) which are NLRP3 modulators for the prevention and treatment of disease states mediated by NLRP3 or conditions in which interleukin 1b activity is implicated, including inflammation, gouty arthritis, type 2 diabetes, atherosclerosis, and liver fibrosis. More particularly, embodiments of the present invention are useful as therapeutics in the treatment of a variety of pathological conditions including (but not limited to) lymphoma, auto-immune diseases, heteroimmune diseases, inflammatory diseases, cancer, and neurodegenerative diseases or conditions.

SUMMARY OF THE INVENTION

The present invention discloses novel compounds as defined by the general formula (I) that are NLRP3 modulators for the prevention and treatment of disease states mediated by NLRP3 as well as treatment of diseases or conditions in which interleukin 1b activity is implicated. The compounds of the present invention are useful in the treatment of human or animal body, by inhibition of NLRP3. The compounds of this invention are therefore suitable for the prevention and treatment of disease states mediated by NLRP3.

EMBODIMENT(S) OF THE INVENTION

An embodiment of the present invention provides novel compounds represented by the general formula (I), their tautomeric forms, their enantiomers, their diastereoisomers, their stereoisomers, their pharmaceutically acceptable salts and pharmaceutical compositions containing them or their mixtures thereof.

In an another embodiment of the present invention is provided pharmaceutical compositions containing compounds of the general formula (I), their tautomeric forms, their enantiomers, their diastereoisomers, their stereoisomers, their pharmaceutically acceptable salts, or their mixtures in combination with suitable carriers, solvents, diluents and other media normally employed in preparing such compositions.

In a further embodiment is provided the use of compounds of the present invention as NLRP3 modulators, by administering a therapeutically effective and non-toxic amount of compounds of general formula (I) or their pharmaceutically acceptable compositions to the mammals. In a still further embodiment compound of formula (I) of the present invention may be used in combination with one or more suitable pharmaceutically active agents.

In another further embodiment is provided a process for preparing the novel compounds of the present invention.

DESCRIPTION OF THE INVENTION

Accordingly, the present invention relates to the compounds of the general formula (I)

Formula (I)

their tautomeric forms, their stereoisomers, their enantiomers, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them wherein

Each of R1 and R2 at each occurrence independently represents hydrogen, halogen, haloalkyl, cyano, optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-

C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylSO2(C1-C6)alkyl, (C1-C6)alkylN(C1-C6)alkyl, (C1-C6)alkylN(C3-C7)cycloalkyl, aryl, heteroaryl, heterocyclyl, benzyl, tert-butyloxycarbonyl, thiol, mercaptoalkyl, SO2(C1-C6)alkyl, SO2(C3-C7)cycloalkyl, SO2-aryl, SO2-heterocyclyl, (C1-C6)thioalkyl, (C1-C6)thioalkoxy, (C1-C6)alkylSO2NH2, -CONH2, -CO(C1-C6)alkyl, -CO(C1-C6)haloalkyl, CO(O)(C1-C6)alkyl, -CO-aryl, -CO-heteroaryl, -CO-heterocyclyl, 4- to 7-membered heterocyclic ring, 7- to 14-membered bicyclic heterocyclic ring system, bridged or spiro ring system having optionally one or more than one heteroatoms; Alternatively R1 , R2 and N together may form a saturated or partially saturated 3 to 8 membered heterocyclic ring system, 7- to 14-membered bicyclic heterocyclic ring system, bridged or spiro ring system having optionally one or more than one heteroatoms;

Each of R3 and R4 at each occurrence represents hydrogen, halogen, haloalkyl, cyano, nitro, amide, sulphonamide, acyl, hydroxyl, optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, SO2(C1-C6)alkyl, thiol, mercapto alkyl benzyl, aryl, heteroaryl, heterocyclyl; Alternatively R3 and R4 may forms a bond;

X is O, N-R6; wherein R6 at each occurrence independently represents hydrogen, hydroxyl, halogen, nitro, cyano, haloalkyl, optionally substituted groups selected from (C1-C10)alkyl, (C1-C10)alkoxy, (C3-C10)cycloalkyl, (C2-C10) alkenyl, (C2-C10)alkynyl, SO2(C1-C6)alkyl, thiol, thioalkyl, thio-alkoxy, SO2(C1-C6)alkyl, SO(C1-C6)alkyl, benzyl, aryl, heteroaryl, heterocyclyl;

n, is independently selected from integer 0-3;

R5 at each occurrence independently represents hydrogen, halogen, haloalkyl, cyano, optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C3-C7)cycloalkyl, benzyl, aryl, heteroaryl, heterocyclyl, thiol, thioalkyl, thio-alkoxy, SO2(C1-C6)alkyl, SO(C1-C6)alkyl, bridged or spiro ring system having optionally one or more than one heteroatoms;

‘A’ is selected from the following ring system

wherein X, Y, Z at each occurrence independently represents C, N, S, SO2, and O, which may be optionally substituted;

Each of R7, R8, R9, R10

, R11 and R12 at each occurrence are independently selected from hydrogen, halogen, cyano, amide, sulphonamide, acyl, hydroxyl, optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, benzyl, aryl, heteroaryl, heterocyclyl; Alternatively each of R8 and R9

, R9 and R10, R10 and R11 and R11 and R12 wherever possible, together may form a 4 to 7 membered saturated or partially saturated ring containing from 0-2 additional heteroatoms selected from the group consisting of N, O, and S(O)p; p = 1-2.

When any of above defined group is substituted the substitutions on them may be selected from those described above or may be selected from hydrogen, hydroxy, cyano, halo, haloalkyl, haloalkyloxy, alkylthio, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3- C10)cycloalkyl, C1-(C1-C6)alkoxy, aryl, heterocyclyl, heteroaryl, -COR11, -CSR11, C(O)OR11, C(O)-R11, -C(O)-NR11R12, -C(S)-NR11R12, -SO2R11 group, wherein each of, R11 and R12 is independently selected from hydrogen, optionally substituted group selected from (C1- C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, aryl, heteroaryl, heterocyclyl groups;

In a preferred embodiment each of R3 and R4 at each occurrence independently selected from hydrogen, halogen, optionally substituted group selected from (C1-C6)alkyl;

In a preferred embodiment R5 at each occurrence independently represents hydrogen, halogen, optionally substituted group selected from (C1-C6)alkyl;

In a preferred embodiment R6 at each occurrence independently represents hydrogen, cyano; In a preferred embodiment each of R7, R8, R9, R10

, R11 and R12 at each occurrence independently selected from hydrogen, halogen, hydroxy optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)haloalkyl;

In a preferred embodiment, the groups, radicals described above may be selected from: "Alkyl", as well as other groups having the prefix "alk", such as alkoxy and alkanoyl, means a carbon chain which may further be substituted with an oxygen atom as is well understood by a skilled artisan, which may further be either linear or branched, and combinations thereof, unless the carbon chain is defined otherwise. Examples of alkyl group include but not limited to methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert. -butyl, pentyl, hexyl etc. where the specified number of carbon atoms permits e.g. from C3-10, the term alkyl also includes cycloalkyl groups, and combinations of linear or branched alkyl chains combined with cycloalkyl structures. When no number of carbon atoms is specified, C1-6 is intended. Substituted alkyl includes alkyl substituted with one or more moieties selected from the group consisting of halo {e.g., CI, F, Br, and I); halogenated alkyl {e.g., CF3, 2-Br-ethyl, CH2F, CH2CI, CH2CF3, or CF2CF3); hydroxyl; amino; carboxylate; carboxamido; alkylamino; arylamino; alkoxy; aryloxy; nitro; azido; cyano; thio; sulfonic acid; sulfate; phosphonic acid; phosphate; and phosphonate as well as those described under the definition of ‘Optionally substituted’.

"Alkenyl" means carbon chains which contain at least one carbon-carbon double bond, and which may be linear or branched or combinations thereof, unless the carbon chain is defined otherwise. Examples of alkenyl include but not limited to vinyl, allyl, isopropenyl, hexenyl, pentenyl, heptenyl, 1 -propenyl, 2-butenyl, 2-methyl -2-butenyl etc. where the specified number of carbon atoms permits, e.g., from C5-10, the term alkenyl also includes cycloalkenyl groups and combinations of linear, branched and cyclic structures. When no number of carbon atoms is specified, C2-6) is intended.

"Alkynyl" means carbon chains which contain at least one carbon-carbon triple bond, and which may be linear or branched or combinations thereof. Examples of alkynyl include ethynyl, propargyl, 3-methyl- l -pentynyl etc. When no number of carbon atoms is specified, is intended.

the “thioalkyl” group used either alone or in combination with other radicals, denotes an alkyl group, as defined above, attached to a group of formula –SR’, (sulfur and its oxidized forms) where R’ represents hydrogen, alkyl or aryl group, e.g. thiomethyl, methylthiomethyl, phenylthiomethyl and the like, which may be optionally substituted.

As used herein, "carbocycle" or "carbocyclic residue" is intended to mean any stable monocyclic or bicyclic or tricyclic ring, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl,
We claim:

1. Compound having the structure of general formula (I)

Formula (I)

their tautomeric forms, their stereoisomers, their enantiomers, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them wherein

Each of R1 and R2 at each occurrence independently represents hydrogen, halogen, haloalkyl, cyano, optionally substituted groups selected from (C1-C6)alkyl, (C1- C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1- C6)alkylSO2(C1-C6)alkyl, (C1-C6)alkylN(C1-C6)alkyl, (C1-C6)alkylN(C3-C7)cycloalkyl, aryl, heteroaryl, heterocyclyl, benzyl, tert-butyloxycarbonyl, thiol, mercaptoalkyl, SO2(C1-C6)alkyl, SO2(C3-C7)cycloalkyl, SO2-aryl, SO2-heterocyclyl, (C1-C6)thioalkyl, (C1-C6)thioalkoxy, (C1-C6)alkylSO2NH2, -CONH2, -CO(C1-C6)alkyl, -CO(C1- C6)haloalkyl, CO(O)(C1-C6)alkyl, -CO-aryl, -CO-heteroaryl, -CO-heterocyclyl, 4- to 7- membered heterocyclic ring, 7- to 14-membered bicyclic heterocyclic ring system, bridged or spiro ring system having optionally one or more than one heteroatoms; Alternatively R1 , R2 and N together may form a saturated or partially saturated 3 to 8 membered heterocyclic ring system, 7- to 14-membered bicyclic heterocyclic ring system, bridged or spiro ring system having optionally one or more than one heteroatoms;

Each of R3 and R4 at each occurrence represents hydrogen, halogen, haloalkyl, cyano, nitro, amide, sulphonamide, acyl, hydroxyl, optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, SO2(C1-C6)alkyl, thiol, mercapto alkyl benzyl, aryl, heteroaryl, heterocyclyl; Alternatively R3 and R4 may forms a bond;

X is O, N-R6; wherein R6 at each occurrence independently represents hydrogen, hydroxyl, halogen, nitro, cyano, haloalkyl, optionally substituted groups selected from (C1-C10)alkyl, (C1-C10)alkoxy, (C3-C10)cycloalkyl, (C2-C10) alkenyl, (C2-C10)alkynyl, SO2(C1-C6)alkyl, thiol, thioalkyl, thio-alkoxy, SO2(C1-C6)alkyl, SO(C1-C6)alkyl, benzyl, aryl, heteroaryl, heterocyclyl;

n, is independently selected from integer 0-3;

R5 at each occurrence independently represents hydrogen, halogen, haloalkyl, cyano, optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C3-C7)cycloalkyl, benzyl, aryl, heteroaryl, heterocyclyl, thiol, thioalkyl, thio-alkoxy, SO2(C1-C6)alkyl, SO(C1-C6)alkyl, bridged or spiro ring system having optionally one or more than one heteroatoms;

‘A’ is selected from the following ring system

wherein X, Y, Z at each occurrence independently represents C, N, S, SO2, and O, which may be optionally substituted;

Each of R7, R8, R9, R10

, R11 and R12 at each occurrence are independently selected from hydrogen, halogen, cyano, amide, sulphonamide, acyl, hydroxyl, optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, benzyl, aryl, heteroaryl, heterocyclyl; Alternatively each of R8 and R9 R9 10 10

, and R , R and R11 and R11 and R12 wherever possible, together may form a 4 to 7 membered saturated or partially saturated ring containing from 0-2 additional heteroatoms selected from the group consisting of N, O, and S(O)p; p = 1-2.

The compound as claimed in claim 1, wherein R3 and R4 at each occurrence is independently selected from hydrogen, halogen, optionally substituted group selected from (C1-C6)alkyl.

The compound as claimed in claim 1, wherein R5 at each occurrence is independently selected from hydrogen, halogen, optionally substituted groups selected from (C1- C6)alkyl.

The compound as claimed in claim 1, wherein R6 at each occurrence is independently selected from optionally substituted groups selected from hydrogen, cyano.

The compound as claimed in claim 1, wherein each of R7, R8, R9, R10, R11 and R12 at each occurrence is independently selected from hydrogen, halogen optionally substituted groups selected from (C1-C6)alkyl, (C1-C6)haloalkyl;

The compound as claimed in any preceding claim, wherein when any of the above group is substituted, the substitutions are selected from hydrogen, hydroxy, cyano, halo, haloalkyl, haloalkyloxy, alkylthio, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C10)cycloalkyl, C1-(C1-C6)alkoxy, aryl, heterocyclyl, heteroaryl, -COR11, -CSR11, C(O)OR11, C(O)-R11, -C(O)-NR11R12, -C(S)-NR11R12, -SO2R11 group, wherein each of, R11 and R12 is independently selected from hydrogen, optionally substituted group selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, aryl, heteroaryl, heterocyclyl groups;

A compound as claimed in claim 1 selected from the group comprising of:

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(isopropylamino)prop-1-ene-1-sulfonamide;

(E)-3-(dimethylamino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methyl(propyl)amino)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(propylamino)prop-1-ene-1-sulfonamide;

(E)-3-((cyclopropylmethyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonamide;

(E)-3-((cyclopropylmethyl)(methyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonamide;

(E)-3-(ethyl(methyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(N-methylmethylsulfonamido)prop-1-ene-1-sulfonamide;

(E)-N-(3-(N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamoyl)allyl)-N-methylcyclopropanesulfonamide;

(E)-N-(3-(N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamoyl)allyl)-N-methylcyclohexanesulfonamide;

(E)-N-(3-(N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamoyl)allyl)cyclohexanesulfonamide;

(E)-3-((cyclohexylmethyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonamide;

(E)-3-((cyclohexylmethyl)(methyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonamide;

(E)-N-(3-(N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamoyl)allyl)-N-methylcyclohexanecarboxamide;

(E)-N-(3-(N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamoyl)allyl)-N-methylacetamide;

(E)-N-(3-(N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamoyl)allyl)-N-methylcyclopropanecarboxamide;

(E)-N-((2,6-diisopropylphenyl)carbamoyl)-3-(dimethylamino)prop-1-ene-1-sulfonamide; (E)-N-((2,6-diisopropyl-4-methylphenyl)carbamoyl)-3-(dimethylamino)prop-1-ene-1-sulfonamide;

(E)-3-(dimethylamino)-N-((4-fluoro-2,6-diisopropylphenyl)carbamoyl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methyl(phenyl)amino)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(phenylamino)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(thiazol-2-ylamino)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methyl(thiazol-2-yl)amino)prop-1-ene-1-sulfonamide;

(E)-N'-cyano-3-(dimethylamino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-N'-cyano-3-(ethyl(methyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-N'-cyano-3-((cyclopropylmethyl)(methyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-N'-cyano-3-((cyclopropylmethyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-N'-cyano-3-(dimethylamino)-N-((4-fluoro-2,6-diisopropylphenyl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-3-((cyclopropylmethyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-3-((cyclopropylmethyl)(methyl)amino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-3-(dimethylamino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-3-(dimethylamino)-N-((4-fluoro-2,6-diisopropylphenyl)carbamoyl)prop-1-ene-1-sulfonimidamide;

(E)-3-(dimethylamino)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-N'-methylprop-1-ene-1-sulfonimidamide;

(E)-N'-cyano-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methyl(oxetan-3-yl)amino)prop-1-ene-1-sulfonimidamide;

(E)-N'-cyano-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(oxetan-3-ylamino)prop-1-ene-1-sulfonimidamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(oxetan-3-ylamino)prop-1- ene-1-sulfonimidamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(oxetan-3-ylamino)prop-1- ene-1-sulfonamide

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(5- methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hexahydropyrrolo[3,4- c]pyrrol-2(1H)-yl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(5- (methylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)prop-1-ene-1-sulfonamide; (E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hexahydropyrrolo[3,4- c]pyrrol-2(1H)-yl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(tetrahydro-1H-furo[3,4- c]pyrrol-5(3H)-yl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(3,4,5,6- tetrahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)prop-1-ene-1-sulfonamide;

(E)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(5-(methylsulfonyl)-3,4,5,6- tetrahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)prop-1-ene-1-sulfonamide

or pharmaceutically acceptable salts of any of the compounds above.

8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) as claimed in any of the preceding claims and optionally one or more pharmaceutically acceptable carriers, diluents or excipients.

9. A method of treating diseases medicated by the NLRP3 modulators as well as treatment of diseases or conditions in which interleukin 1β activity and interleukin-18 (IL-18) are implicated which comprising administering to a patient in need thereof an effective amount of a compound of Formula (I) as claimed in any of the preceding claims or its suitable pharmaceutical composition.

10. The use of compounds of formula (I) or its pharmaceutical compositions as claimed in any of the preceding claim suitable for treatment of diseases wherein the NLRP3 modulator has a pathophysiological function.

11. The pharmaceutical composition as claimed in claims 8 in combination with one or more suitable pharmaceutically active agents selected from Inhibitors of interleukin-1β; immune-suppressants; metabolic disorders drugs, glucocorticoids, non-steroidal anti- inflammatory drugs, COX-2 specific inhibitors, anti-inflammatory drugs, TNF-α binding proteins, interferon-13, interferon, interleukin-2, antihistamines, beta-agonist, BTK inhibitors, anticolinergics, anti-cancer agents or their suitable pharmaceutically acceptable salts, Non-Alcoholic Steato- Hepatitis (NASH) and fibrosis drugs, anticancer drugs, antibiotics, hormones, aromatase inhibitors, inhibitors of mitogen-activated protein kinase signaling, Syk inhibitors, mTOR inhibitors, BCR/ABL antagonists, Arenaviridae virus infections, particularly Lassa virus and Junin virus infections, antibiotic and/or antifungal prophylaxis, fever and pain medication, antiemetic and/or antidiarrheal agents, vitamin and mineral supplements, anti-inflammatory agents, anti-inflammatory and immunosuppressant agents, pain medications, and medications for other common diseases in the patient population, anti-malarial agents and cephalosporin antibiotics.