The invention relates to inhibitors of Janus Kinase 1 (JAK1), a process for synthesis of the compounds of the present invention, composition comprising the compounds and use of the compounds for inhibition of JAK1.

BACKGROUND OF THE INVENTION

Cytokines are key drivers of several biological pathways and anti-cytokine therapy is indicated if there is any dysregulation in the pathway. Signalling pathways for Type I and Type II cytokine receptors, a family of receptors employed by over 50 cytokines, interleukins, interferons, colony stimulating factors, and hormones. Like other receptor super families, Type I and Type II cytokine receptors are related by their mode of intracellular signaling: they all employ JAKs. Janus Kinases (JAK) are intracellular tyrosine kinases linked to intracellular domains of many cytokine receptors. There are four JAK isoforms: JAK1, JAK2, JAK3 and TYK2. JAK1, JAK2, JAK3 and Tyrosine Kinase 2 (TYK2) bind directly to the intracellular domains of Type I/II cytokine receptors and not to other classes of cytokine receptors. Different cytokine receptor families utilize specific JAK isoforms for signal transduction. Phosphorylation of JAK when cytokine binds to its cognate receptor leads to phosphorylation of other intracellular molecules that eventually leads to gene transcription. JAK-dependent cytokines are major contributors to immunopathology and that blocking such cytokines with biologics can be beneficial in immune-mediated diseases and in cancers and several other major disease and disorders.

Several inhibitors of JAK kinase exist. They block multiple JAKs and therefore inhibit the actions of a large variety of cytokines and several pan-JAK inhibitors continue to be developed. The JAK isoforms vary in function, and therefore there exists a need in the art for isoform-specific inhibitors that can reduce undesired effects from the administration of generalized JAK inhibitors. JAK1 plays a key role in types I and II interferon signaling and elicits signals from the interleukin-2, interleukin-4, gp130 and class II receptor families. As such, small molecule inhibition of JAK1 may intervene in the signaling pathways involved in oncology, inflammation and autoimmune diseases. However, to minimize adverse effects, especially those arising from JAK2 inhibition, the generation of selective inhibitors could in principle maintain efficacy and improve safety.

OBJECT OF THE INVENTION

An object of the invention is to provide compounds as selective JAK1 inhibitor, a process for preparation of the inhibitors, a composition containing the compounds and utility of the compounds.

SUMMARY OF THE INVENTION

The present invention discloses 1H-imidazo[4,5-b]pyridin-2(3H)-one as selective inhibitor of JAK 1 their pharmaceutically acceptable salts and isomers of formula I:

Wherein;
A is a 5 membered or a 6 membered carbocycle or heterocycle comprising 1 to 3 heteroatom selected from the group comprising O, N, S optionally substituted with CH3, F or Cl;

B is H or alkoxy or O, -CO-, optionally substituted 3 to 8 carbocyclic ring, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S,

X is independently, H, (CH2)n, -CO-, OCO, COO; CO(CH2)n, (NH2)n; (CH2)n(NH2)n; (CH2)n(NH2)nCN; CONH; CONR1R2, CO(NH2)n; (CH2)nCO(NH2)n, CO(NH2)n(CH2)CF3, SO2(CH2)n, NH(CH2)nCN, unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S and SO2, and substituents on the carboxylic or heterocyclic ring may be selected from Halogen, Alkoxy, CHMe, -CH(CF3), - C(CF3)(OH), C(CF3)(OMe), -CH(CN), CHOH, CH(R5),

Y may be absent or may be selected from H, R1, R2, halo, , C1-C6 Alkyl, C1-C6 Alkoxy CN, -CO-, COR1, (CH2)n, -(CH2)nCN -, CH2CF3, COOH, OR1, NR1R2, -COOR1, - CON(R1)2,-SO2(CH2)n,-SO2N(R1)2, -OCOR1, CONHCH(CH3)-CF3, CH2CN,

CH2SO2CH3 -NR1COR1, -CONH, CONR1R2, -CO(NH2)n(CH2)nSO2; -CONH(CH2)nOH, CONH(CH2)nSO2R1R2, -CONH-(CH2)nCF3, -CONH(CH2)nCF3,-NHCONH(CH2)nCF3, NHCONHR1, -NHCOR1R2, NR1CONR1R2, (NH2)n, -NH2CH2, NH2CH2CF3,-CH(CF3)-(CH)n-CO-N-R1R2,CH(CF3)-(CH)n-SO2,

(CH)n;CH(OH)(CF3)(Heretocycle)R1, optionally substituted 3 to 8 membered carbocyclic ring, or 3 to 8 membered saturated, mono-, fused- or bridged heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, optionally substituted 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, wherein the substitution may independently be R1 and R2 at any position of the ring;C1-6alk-aryl, ArC1-6alkyl;

R1 and R2 are independently selected from the group comprising H, halo, CN, CF3, hydroxyl, Amino, SO2, SO2, C1-C6 Alkyl, SO2-C3-C8-cycloalkyl, CH2CN, CH2CF3, unsubstituted or substituted C1-C6 straight or branched alkyl wherein the substituents are selected from halo, OH, CN, C1-C6 alkoxy, optionally substituted NH2, C1-C6 alkylsulfonyl, optionally substituted CONH2, unsubstituted or substituted C3-C8 carbocyclyl or 3-8 membered heterocyclic ring with 1-3 heteroatoms selected from O, N and S, SO2, C1-C6 straight or branched alkenyl, C1-C6 straight or branched alkynyl, , C1-C6 alkyloxy; C1-C6 alkylamino, C1-C6 alkylcarbonyl, C(O)-C3-C8-cycloalkyl, heteroalkyl, optionally substituted CONH2, C3–C8 cycloalkyl, C3–C8cycloalkenyl, C3– C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl, -CH(CF3)-(CH)n-CO-N-R3R4, -CH(CF3)-(CH)n-SO2-NR3R4, CH(CF3)-(CH)n-NR3R4, CH(CF3)-NR3R4, CH(CF3)-(CH)n-SO2-CHR3R4, wherein cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, carbocyclyl, aryl and heteroaryl groups are optionally substituted;

R3 and R4 are H, independently CH3, C3–C8 cycloalkyl;

R5 is unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1to 3 heteroatoms selected from the group comprising O, N, S, SO2;

R6, is independently H, C1-C6 straight or branched alkyl, halogen;

X can be connected to Y at any atom so as to arrive at chemically viable bond;

n is 0 to 3.

The present invention also discloses a process for preparing the compounds of the present invention, a composition comprising the compounds of the present invention and utility of the compounds of the present invention as selective JAK1 inhibitors.

BRIEF DESCRIPTION OF FIGURES

Figure 1 depicts cumulative Psoriasis Score and body weight of Example 1133 and 1215 in IMQ induced psoriasis mouse model. Figure 1a is based on the Psoriasis Score. Data is shown as Mean ± S.E.M.(n=8), * Significant difference as compared to Vehicle Control group. # Significant difference as compared to Naive Control group. Two-way ANOVA followed by Bonferroni Test. **P < 0.01 & ###/***P < 0.001. Figure 1(b) pertains to the body weight. Data is shown as Mean ± S.E.M.(n=8), # Significant difference as compared to Naive control. Two-way ANOVA followed by Bonferroni Test #P < 0.05.

DETAILED DESCRIPTION OF THE INVENTION

The present invention discloses 1H-imidazo[4,5-b]pyridin-2(3H)-one as selective inhibitor of JAK 1 their pharmaceutically acceptable salts and isomers of formula I:

Wherein;

A is a 5 membered or a 6 membered carbocycle or heterocycle comprising 1 to 3 heteroatom selected from the group comprising O, N, S optionally substituted with CH3, F or Cl;

B is H or alkoxy or O, -CO-, optionally substituted 3 to 8 carbocyclic ring, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S,

X is independently, H, (CH2)n, -CO-, OCO, COO; CO(CH2)n, (NH2)n; (CH2)n(NH2)n; (CH2)n(NH2)nCN; CONH; CONR1R2, CO(NH2)n; (CH2)nCO(NH2)n, CO(NH2)n(CH2)CF3, SO2(CH2)n, NH(CH2)nCN, unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S and SO2, and substituents on the carboxylic or heterocyclic ring may be selected from Halogen, Alkoxy, CHMe, -CH(CF3), -C(CF3)(OH), C(CF3)(OMe), -CH(CN), CHOH, CH(R5),

Y may be absent or may be selected from H, R1, R2, halo, , C1-C6 Alkyl, C1-C6 Alkoxy CN, -CO-, COR1, (CH2)n, -(CH2)nCN -, CH2CF3, COOH, OR1, NR1R2, -COOR1, -CON(R1)2,-SO2(CH2)n,-SO2N(R1)2, -OCOR1, CONHCH(CH3)-CF3, CH2CN, CH2SO2CH3 -NR1COR1, -CONH, CONR1R2, -CO(NH2)n(CH2)nSO2; -CONH(CH2)nOH, CONH(CH2)nSO2R1R2, -CONH-(CH2)nCF3, -CONH(CH2)nCF3,-NHCONH(CH2)nCF3, NHCONHR1, -NHCOR1R2, NR1CONR1R2, (NH2)n, -NH2CH2, NH2CH2CF3,-CH(CF3)-(CH)n-CO-N-R1R2,CH(CF3)-(CH)n-SO2, (CH)n;CH(OH)(CF3)(Heretocycle)R1, optionally substituted 3 to 8 membered carbocyclic ring, or 3 to 8 membered saturated, mono-, fused- or bridged heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, optionally substituted 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, wherein the substitution may independently be R1 and R2 at any position of the ring;C1-6alk-aryl, ArC1-6alkyl;

R1 and R2 are independently selected from the group comprising H, halo, CN, CF3, hydroxyl, Amino, SO2, SO2, C1-C6 Alkyl, SO2-C3-C8-cycloalkyl, CH2CN, CH2CF3, unsubstituted or substituted C1-C6 straight or branched alkyl wherein the substituents are selected from halo, OH, CN, C1-C6 alkoxy, optionally substituted NH2, C1-C6 alkylsulfonyl, optionally substituted CONH2, unsubstituted or substituted C3-C8 carbocyclyl or 3-8 membered heterocyclic ring with 1-3 heteroatoms selected from O, N and S, SO2, C1-C6 straight or branched alkenyl, C1-C6 straight or branched alkynyl, , C1-C6 alkyloxy; C1-C6 alkylamino, C1-C6 alkylcarbonyl, C(O)-C3-C8-cycloalkyl, heteroalkyl, optionally substituted CONH2, C3–C8 cycloalkyl, C3– C8cycloalkenyl, C3–C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl, -CH(CF3)-(CH)n-CO-N-R3R4, -CH(CF3)-(CH)n-SO2-NR3R4, CH(CF3)-(CH)n-NR3R4, CH(CF3)-NR3R4, CH(CF3)-(CH)n-SO2-CHR3R4, wherein cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, carbocyclyl, aryl and heteroaryl groups are optionally substituted;

R3 and R4 are H, independently CH3, C3–C8 cycloalkyl;

R5 is unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S, SO2;

R6, is independently H, C1-C6 straight or branched alkyl, halogen;

X can be connected to Y at any atom so as to arrive at chemically viable bond;

n is 0 to 3.

The compounds disclosed herein and their pharmaceutically acceptable salts can exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. The compounds disclosed herein can also exist as geometric isomers. All such single stereoisomers, racemates and mixtures thereof, and geometric isomers are intended to be within the scope of the compounds disclosed herein.

Exemplary compounds of the present invention of Formula I are illustrated herein below at Table 1.

Table 1: Exemplary compounds of the present invention

The compounds of the present invention include:

1001. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)benzamide;

1002. 1-(1,1,1-trifluoropropan-2-yl)-3-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)urea;

1003. 1-(2,2,2-trifluoroethyl)-3-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)urea;

1004. 1-(2,2,2-trifluoroethyl)-3-(5-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)pyrimidin-2-yl)urea;

1005. 1-(2,2,2-trifluoroethyl)-3-(5-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)pyridin-2-yl)urea;

1006. 1-(5-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)pyrazin-2-yl)-3-(2,2,2-trifluoroethyl)urea;

1007. N-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)-3,3-dimethylazetidine-1-carboxamide;

1008. N-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)morpholine-4-carboxamide;

1009. 1-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)-3-(pyridin-4-yl)urea; 1010. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-3-(2,2,2-trifluoroethyl)urea;

1011. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1012. N-(cyanomethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1013. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2-(methylsulfonyl)ethyl)piperazine-1-carboxamide;

1014. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(pyridin-4-yl)piperazine-1-carboxamide;

1015. N-(2-fluoropyridin-4-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1016. N-(1-(methylsulfonyl)piperidin-4-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1017. N-(cyclopentylmethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1018. 7-(4-(1,1-dioxidothiomorpholine-4-carbonyl)piperazin-1-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one;

1019. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2-methoxypyridin-4-yl)piperazine-1-carboxamide;

1020. N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1021. N-(1,1,1-trifluoropropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1022. N-(2,2,2-trifluoroethyl)-4-(2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1023. 7-(4-(3,3-dimethylazetidine-1-carbonyl)piperazin-1-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one;

1024. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2-methyl-4-(methylsulfonyl)phenyl)piperazine-1-carboxamide;

1025. N-(2,2,2-trifluoroethyl)-2-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)acetamide;

1026. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1027. N-(cyanomethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1028. N-(2,2,2-trifluoroethyl)-3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrrole-1-carboxamide;

1029. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-1-methyl-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1030. N-(1,1,1-trifluoropropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1031. 7-(1-(4,4,4-trifluorobutanoyl)-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one; 1032. N-(1-cyanocyclopropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1033. N-(2-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1034. N-(cyclopentylmethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1035. N-(cyanomethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide hydrochloride;

1036. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)-1H-pyrazole-1-carboxamide;

1037. 7-(1-(3,3-dimethylazetidine-1-carbonyl)-1H-pyrazol-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one;

1038. N-(cyano(cyclopentyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1039. N-(2-cyano-1-cyclopentylethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1040. N-(2-cyanobutan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1041. N-(1-cyclopentyl-2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1042. 4-(1-ethyl-2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide;

1043. N-(cyano(cyclopropyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1044. N-(1-cyano-2-methylpropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1045. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazole-1-carboxamide;

1046. N-(1-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1047. N-((S)-1-cyano-2-methylpropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1048. 1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)azetidine-3-carbonitrile;

1049. N-((R)-1-cyano-2-methylpropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1050. N-(3-cyano-1,1,1-trifluoropropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1051. N-(2-cyano-1-cyclopropylethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1052. N-(1-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1053. N-(1-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1054. N-((R)-cyano(cyclopropyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1055. 1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile;

1056. N-(3-cyanocyclobutyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1057. 2-(1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidin-3-yl)acetonitrile;

1058. N-(1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1059. N-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1060. N-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1061. 3-(1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidin-3-yl)propanenitrile;

1062. N-(2-cyano-1-(tetrahydro-2H-pyran-4-yl)ethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1063. N-(cyano(phenyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1064. N-(2,2,2-trifluoroethyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1065. N-(2-cyano-1-(tetrahydro-2H-pyran-4-yl)ethyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1066. N-(2-cyanocyclohexyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1067. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)piperidine-4-carbonitrile;

1068. N-(1-(3-cyanoazetidin-1-yl)propan-2-yl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1069. N-(1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidin-3-yl)propane-1-sulfonamide;

1070. N-(cyano(phenyl)methyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1071. N-(1-cyano-3-methoxypropyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1072. N-(1-cyano-3-(methylsulfonyl)propyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1073. N-((S)-1-cyano-2-methylpropyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1074. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)-4-methylpyrrolidine-3-carbonitrile;

1075. 2-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)oxazol-4-yl)acetonitrile; 1076. 2-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)thiazol-4-yl)acetonitrile; 1077. 7-(1-((oxazol-5-yl)methyl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1078. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)acetonitrile; 1079. 6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridine-3-carbonitrile;

1080. 7-(1-(5-((methylsulfonyl)methyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1081. 7-(1-(5-((oxetan-3-yl)methyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1082. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)acetonitrile hydrochloride;

1083. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methanol; 1084. 7-(1-(5-(2,2,2-trifluoroethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1085. 7-(1-(5-(morpholinomethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1086. 4-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methyl)thiomorpholine 1,1-dioxide;

1087. 1-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methyl)azetidine-3-carbonitrile;

1088. 6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-N-(cyanomethyl)pyridine-3-carboxamide;

1089. N-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methyl)methanesulfonamide;

1090. N-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methyl)methanesulfonamide;

1091. N-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methyl)-2-cyanoacetamide;

1092. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-N-(2,2,2-trifluoroethyl)acetamide;

1093. 2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-N-(cyanomethyl)pyrimidine-5-carboxamide;

1094. N-(2,2,2-trifluoroethyl)-4-(2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1095. 4-(2-ethoxy-3H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide;

1096. 4-(2-cyclopropyl-3H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide;

1097. 3-(4-(2-(4-chloro-3-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-tetrahydro-2H-pyran-4-carbonitrile;

1098. 4-(2-(1-acetylpiperidin-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide;

1099. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)acetonitrile;

1100. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2-cyclopropylacetonitrile;

1101. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2-morpholinoacetonitrile;

1102. N-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2-cyanoacetamide; 1103. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-3-fluorophenyl)acetonitrile;

1104. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-2-fluorophenyl)acetonitrile;

1105. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-2-methoxyphenyl)acetonitrile;

1106. 2-(3-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)acetonitrile;

1107. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)propanenitrile; 1108. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)propanamide; 1109. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)cyclopropanecarbonitrile;

1110. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-cyclopropylacetonitrile;

1111. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(3,3-difluoroazetidin-1-yl)acetonitrile;

1112. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-morpholinoacetonitrile;

1113. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1-dioxidothiomorpholino)acetonitrile;

1114. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1-(methylsulfonyl)azetidin-3-yl)acetonitrile;

1115. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1-(methylsulfonyl)azetidin-3-yl)acetonitrile;

1116. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4-(methylsulfonyl)butanenitrile;

1117. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-2-yl)acetonitrile; 1118. 2-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-4-yl)acetonitrile; 1119. 7-(1-(5-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1120. 7-(1-(5-(1-chloro-2,2,2-trifluoroethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1121. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-N,N-dimethylethanamine;

1122. 7-(1-(5-(1,1,1-trifluorobutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1123. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutanenitrile;

1124. 7-(1-(5-(2,2,2-trifluoro-1-isopropoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1125. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1-trifluoropropan-2-ol;

1126. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol;

1127. 7-(1-(5-(1-cyclopropyl-2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1128. 7-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1129. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1-trifluoro-3-methylbutan-2-ol;

1130. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclohexyl-2,2,2-trifluoroethanol;

1131. 1-(4-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-hydroxyethyl)piperidin-1-yl)ethanone;

1132. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopentyl-2,2,2-trifluoroethanol;

1133. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-methylpiperidin-4-yl)ethanol;

1134. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(tetrahydro-2H-pyran-4-yl)ethanol;

1135. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(piperidin-4-yl)ethan-1-ol

1135. 7-(1-(5-(2,2,2-trifluoro-1-(oxetan-3-yl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1136. 7-(1-(5-(2,2,2-trifluoro-1-morpholinoethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1137. 7-(1-(5-(1,1,1-trifluoro-3-(methylsulfonyl)propan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1138. 7-(1-(5-(4-(cyclopropylsulfonyl)-1,1,1-trifluorobutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1139. 7-(1-(5-(1-((methylsulfonyl)methoxy)-2,2,2-trifluoroethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1140. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutane-1-sulfonamide;

1141. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutane-1-sulfonamide;

1142. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)methanesulfonamide;

1143. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N,N-dimethylbutanamide;

1144. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutanamide;

1145. 1-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethyl)-3-cyclopropylurea;

1146. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

1147. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoro-N-methylpentanamide;

1148. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)cyclopropanecarboxamide;

1149. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-N-cyclopropyl-5,5,5-trifluoropentanamide;

1150. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)cyclopentanecarboxamide;

1151. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutan-1-amine;

1152. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)cyclopropanamine;

1153. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutan-1-ol;

1154. 7-(1-(5-(1,1,1-trifluoro-4-methoxybutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1155. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoropentanenitrile;

1156. 2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethoxy)acetonitrile;

1157. 7-(1-(5-(1-(methylsulfonyl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1158. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(cyclopropyl)methanol;

1159. 7-(1-(5-(3-(methylsulfonyl)-1-(oxetan-3-yl)propyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1160. 7-(1-(5-(1-methoxy-3-(methylsulfonyl)propyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1161. 7-(1-(5-(1-fluoro-3-(methylsulfonyl)propyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1162. 7-(1-(5-(4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1163. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanol;

1164. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-methylpiperidin-4-yl)methanol;

1165. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-N-(2,2,2-trifluoroethyl)-2-hydroxyacetamide;

1166. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-cyclopropyl-N-(2,2,2-trifluoroethyl)acetamide;

1167. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-cyano-N-(2,2,2-trifluoroethyl)acetamide;

1168. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethanol;

1169. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-2-yl)-2,2,2-trifluoroethanol;

1170. 7-(1-(6-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1171. 1-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-4-yl)-2,2,2-trifluoroethanol;

1172. 1-(5-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-2-yl)-2,2,2-trifluoroethanol;

1173. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1174. 7-(1-(6-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1175. 7-(1-(4-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1176. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile

1177. 1-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethyl)-3-cyclopropylurea

1178. 1-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)-3-cyclopropylurea

1179. 3-cyclopentyl-3-(4-(2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)propanenitrile

1180. 3-cyclopentyl-3-(4-(2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)propanenitrile

1181. 7-(1-(5-((S)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1182. 7-(1-(5-((R)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1183. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1-trifluoropropan-2-ol

1184. 7-(1-(5-((R)-2,2,2-trifluoro-1-(oxetan-3-yl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1185. 7-(1-(5-((S)-2,2,2-trifluoro-1-(oxetan-3-yl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1186. 7-(1-(5-(1,1,1-trifluoro-4-(isopropylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1187. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-(methyl sulfonyl) 1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethanamine

1188. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-(cyclopropyl amino sulfonyl) 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1189. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

1190. 7-(1-(4-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)phenyl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1191. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(trifluoromethyl)propan-1-ol

1192. N-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethyl)-2-cyanoacetamide

1193. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoro-2-methylpentan-2-ol

1194. 7-(1-(5-(3,3,3-trifluoro-2-((methylsulfonyl)methyl)propyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1195. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)-N-methylcyclopropanamine

1196. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-2,2-dimethylbutan-1-ol

1197. N-(2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethoxy)ethyl)cyclopropanamine

1198. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutan-1-amine

1199. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)cyclohexanamine

1200. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutan-1-amine

1201. 7-(1-(5-(1,1,1-trifluoro-4-morpholinobutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1202. 1-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)azetidine-3-carbonitrile

1203. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-isopropylbutan-1-amine

1204. 7-(1-(5-(4-(cyclopropylmethylsulfonyl)-1,1,1-trifluorobutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1205. 7-(1-(5-(3-(cyclopropylmethylsulfonyl)-1,1,1-trifluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1206. 7-(1-(5-(1,1,1-trifluoro-3-morpholinopropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1207. (S)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-isopropylbutan-1-amine

1208. (R)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-isopropylbutan-1-amine

1209. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-(Methyl sulfonyl)1H-pyrazol-1-yl)pyridin-3-yl)-3,3,3-trifluoropropan-1-amine

1210. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoro-N-isopropylpentanamide

1211. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N,N-diisopropylbutan-1-amine

1212. N-(2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-3,3,3-trifluoropropyl)cyclopropanamine

1213. (R)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutanamide

1214. (S)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutanamide

1215. (S)-4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoro-N-isopropylpentanamide

1216. 7-(1-(5-((S)-4-(cyclopropylsulfonyl)-1,1,1-trifluorobutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1217. (S)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-N-methylbutan-1-amine,TFA salt

1218. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-3,3,3-trifluoro-N-isopropylpropan-1-amine

1219. 7-(1-(5-(1,1,1-trifluoro-4-(4-methylpiperazin-1-yl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1220. (4-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-hydroxyethyl)piperidin-1-yl)(cyclopropyl)methanone

1221. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1-ethylpiperidin-4-yl)-2,2,2-trifluoroethanol

1222. 7-(1-(5-(1,1,1-trifluoro-3-(4-methylpiperazin-1-yl)propan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1223. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-ol

1224. 5-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-6,6,6-trifluorohexan-2-amine,TFA salt

1225. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol

1226. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol

1227. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoro-4-hydroxypentanenitrile

1228. 2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethoxy)-N-methylethanamine

1229. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1-trifluoro-3-morpholinopropan-2-ol

1230. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1-trifluoro-4-morpholinobutan-2-ol

1231. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-methylazetidin-3-yl)ethanol

1232. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1-ethylpyrrolidin-3-yl)-2,2,2-trifluoroethanol

1233. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1-ethylpyrrolidin-3-yl)-2,2,2-trifluoroethanol

1234. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-methylpyrrolidin-3-yl)ethanol

1235. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-methylpyrrolidin-3-yl)ethanol

1236. 1-(3-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-hydroxyethyl)azetidin-1-yl)ethanone

1237. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-isopropylazetidin-3-yl)ethanol

1238. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoro-4-hydroxy-N-isopropylpentanamide

1239. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1-ethylazetidin-3-yl)-2,2,2-trifluoroethanol

1240. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-isopropylpiperidin-4-yl)ethanol

1241. N-(2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoroethoxy)ethyl)propan-2-amine,TFA salt

1242. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-(oxetan-3-yl)pyrrolidin-3-yl)ethanol

1243. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-(oxetan-3-yl)pyrrolidin-3-yl)ethanol

1244. 7-(1-(5-(2,2,2-trifluoro-1-methoxy-1-(1-methylpiperidin-4-yl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1245. 3-(3-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-hydroxyethyl)azetidin-1-yl)-3-oxopropanenitrile

1246. 3-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-hydroxyethyl)-N-methylazetidine-1-carboxamide

1247. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)isobutyramide

1248. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluorobutyl)-2-cyanoacetamide

1249. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4-trifluoro-1-morpholinobutan-1-one

1250. 1-(4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5-trifluoropentanoyl)azetidine-3-carbonitrile

1251. (S)-1-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol

1252. (R)-1-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol

The present invention discloses novel compounds of 1H-imidazo[4,5-b]pyridin-2(3H)-one their pharmaceutically acceptable salts and isomers of formula II:

Wherein;

B is H;

X is independently, H, (CH2)n, -CO-, OCO, COO; CO(CH2)n, (NH2)n; (CH2)n(NH2)n; (CH2)n(NH2)nCN; CONH; CONR1R2, CO(NH2)n; (CH2)nCO(NH2)n, CO(NH2)n(CH2)CF3, SO2(CH2)n, NH(CH2)nCN, unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S and SO2, and substituents on the carboxylic or heterocyclic ring may be selected from Halogen, Alkoxy, CHMe, -CH(CF3), -C(CF3)(OH), C(CF3)(OMe), -CH(CN), CHOH, CH(R5),

H, R1, R2, halo, , C1-C6 Alkyl, C1-C6 Alkoxy CN, -CO-, COR1, (CH2)n, -(CH2)nCN -, CH2CF3, COOH, OR1, NR1R2, -COOR1, -CON(R1)2,-SO2(CH2)n,-SO2N(R1)2, -OCOR1, CONHCH(CH3)-CF3, CH2CN, CH2SO2CH3 -NR1COR1, -CONH, CONR1R2, -CO(NH2)n(CH2)nSO2; -CONH(CH2)nOH, CONH(CH2)nSO2R1R2, -CONH-(CH2)nCF3, -CONH(CH2)nCF3,-NHCONH(CH2)nCF3, NHCONHR1, -NHCOR1R2, NR1CONR1R2, (NH2)n, -NH2CH2, NH2CH2CF3,-CH(CF3)-(CH)n-CO-N-R1R2,CH(CF3)-(CH)n-SO2, (CH)n;CH(OH)(CF3)(Heretocycle)R1, optionally substituted 3 to 8 membered carbocyclic ring, or 3 to 8 membered saturated, mono-, fused- or bridged heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, optionally substituted 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, wherein the substitution may independently be R1 and R2 at any position of the ring;C1-6alk-aryl, ArC1-6alkyl;

R1 and R2 are independently selected from the group comprising H, halo, CN, CF3, hydroxyl, Amino, SO2, SO2, C1-C6 Alkyl, SO2-C3-C8-cycloalkyl, CH2CN, CH2CF3, unsubstituted or substituted C1-C6 straight or branched alkyl wherein the substituents are selected from halo, OH, CN, C1-C6 alkoxy, optionally substituted NH2, C1-C6 alkylsulfonyl, optionally substituted CONH2, unsubstituted or substituted C3-C8 carbocyclyl or 3-8 membered heterocyclic ring with 1-3 heteroatoms selected from O, N and S, SO2, C1-C6 straight or branched alkenyl, C1-C6 straight or branched alkynyl, , C1-C6 alkyloxy; C1-C6 alkylamino, C1-C6 alkylcarbonyl, C(O)-C3-C8-cycloalkyl, heteroalkyl, optionally substituted CONH2, C3–C8 cycloalkyl, C3– C8cycloalkenyl, C3–C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl, -CH(CF3)-(CH)n-CO-N-R3R4, -CH(CF3)-(CH)n-SO2-NR3R4, CH(CF3)-(CH)n-NR3R4, CH(CF3)-NR3R4, CH(CF3)-(CH)n-SO2-CHR3R4, wherein cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, carbocyclyl, aryl and heteroaryl groups are optionally substituted;

R3 and R4 are H, independently CH3, C3–C8 cycloalkyl;

R5 is unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S, SO2;

R6, is independently H, C1-C6 straight or branched alkyl, halogen;

X can be connected to Y at any atom so as to arrive at chemically viable bond;

n is 0 to 3.

The present invention discloses novel compounds of 1H-imidazo[4,5-b]pyridin-2(3H)-one their pharmaceutically acceptable salts and isomers of formula III:

Wherein;

Y may be present at any position of the pyridine ring, preferably, at 4th or 5th position of pyridine;

Y is H, R1, R2, halo, CN, -CO-, COR1, (CH2)n, -(CH2)nCN -, CH2CF3, COOH, -COOR1, -CON(R1)2,-SO2(CH2)n,-SO2N(R1)2, -OCOR1, -NR1COR1, -CONH, CONR1R2, -CO(NH2)n(CH2)nSO2; -CONH(CH2)nOH, CONH(CH2)nSO2R1R2, -CONH-(CH2)nCF3, -CONH(CH2)nCF3,-NHCONH(CH2)nCF3, , -CH(CF3)-(CH)n-CO-N-R1R2,CH(CF3)-(CH)n-SO2-(CH)n; CH(OH)(CF3)(Heretocycle)R1, NHCONHR1, -NHCOR1R2, NR1CONR1R2, (NH2)n, -NH2CH2-, NH2CH2CF3,

wherein the heterocycle is optionally substituted 3 to 8 membered saturated, mono-, fused- or bridged heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S.

wherein the substitution may independently be R1 and R2 at any position of the heterocyclic ring; C1-6alk-aryl, Ar C1-6 alkyl;

R1 and R2 are absent or independently selected from the group comprising H, halo, CN, CF3, hydroxyl, Amino, SO2, SO2C1-C6 Alkyl, CH2CF3, C1-C6 straight or branched alkyl, C1-C6 straight or branched alkenyl, C1-C6 straight or branched alkynyl, halo-C1-C6 alkyl, C1-C6 alkyloxy; C1-C6 alkylamino,

n is 0 to 3.

The present invention discloses exemplary compounds of formula III as below:

1133.1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-methylpiperidin-4-yl)ethanol;

1134.1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(tetrahydro-2H-pyran-4-yl)ethanol;

1176.1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile

1181.7-(1-(5-((S)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1182.7-(1-(5-((R)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

1225.(R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol

1226.(S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol

1231.1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2-trifluoro-1-(1-methylazetidin-3-yl)ethanol

In an embodiment, the present invention also discloses a process of preparing the compounds of the present invention. The compounds of the present invention can be prepared by the general synthetic schemes 1 to 4, presented here below:

General Synthetic Scheme 1:

Wherein,

X is C, N,

R2 and R3 is H,

R1:

Wherein,

X is C, N,

R1 is CN and R2 is H R3;

Wherein,

X is C, N,

R1 CF3 and R2 is H, R3;

Wherein,

X is C, N,

R1 is CF3 and R2 is OH R3

X is C, N,

R1 is CF3 and R2 is OCH3 R3

General Synthetic Scheme 2:

X1= O or H R2= H or–CH3 R3= H or–CH3 R1;

General Synthetic Scheme 3:

X1, Y, Z is C, N.

R3 is H, O, carbocycle,

General Synthetic Scheme 4:

X is C, N.

R2 is H, O, carbocycle, R1 =

The invention also comprises as another embodiment, a composition comprising a JAK1 inhibitor compound according to any one of the preceding embodiments together with a pharmaceutically acceptable diluent, excipient, and/or carrier. The compositions will include a conventional pharmaceutical carrier, excipient, and/or diluent and a compound of this disclosure as the/an active agent, and, in addition, can include carriers and adjuvants, etc. The pharmaceutically acceptable compositions will contain about 1% to about 99% by weight of a compound(s) of this disclosure, or a pharmaceutically acceptable salt thereof, and 99% to 1% by weight of a suitable pharmaceutical excipient.

Administration of the compounds of this disclosure, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration or agents for serving similar utilities. Thus, administration can be, for example, orally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, intracisternally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, preferably in unit dosage forms suitable for simple administration of precise dosages.

Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. Solid dosage forms, as described above, can be prepared with coatings and shells, such as enteric coatings. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. Compositions for rectal administrations are, for example, suppositories that can be prepared by mixing the compounds of this disclosure with, for example, suitable non-irritating excipients or carriers. They are also be parenteral and administered as sterile powders for reconstitution into sterile injectable solutions or dispersions. Dosage forms for topical administration of a compound of this disclosure include ointments, powders, sprays. Ophthalmic formulations, eye ointments, powders, inhalation formulations and solutions are also contemplated for the compounds in this disclosure. Compressed gases can be used to disperse a compound of this disclosure in aerosol form.

The invention comprises as a further embodiment a method for treating a disease JAK1 mediates or is implicated in a subject in need thereof comprising administrating to the subject a therapeutically effective amount of a JAK1 inhibitor compound according to any one of the

preceding embodiments, or a composition comprising a JAK1 inhibitor according to any one of the preceding embodiments together with a pharmaceutically acceptable diluent, excipient, and/or carrier. The diseases JAK1 mediates or is implicated in that may be treated includes, without limitation, cancer, inflammatory disorders, and autoimmune diseases.

The selective JAK1 inhibitors of the present invention may be effective in treating cancer, including, but not limited to, carcinomas, sarcomas, lymphomas, leukemias, myelomas, germ cell tumors, blastomas, tumors of the central and peripheral nervous system and other tumors including melanomas, seminoma and Kaposi's sarcoma and the like.

The compounds of the present invention may also be useful in disorder and diseases pertaining to acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, asthma, autoimmune hemolytic anemia, autoimmune thyroiditis, Crohn's disease, episodic lymphopenia with lymphocytotoxins, erythroblastosis fetalis, Goodpasture's syndrome, Graves' disease, Hashimoto's thyroiditis, hypereosinophilia, irritable bowel syndrome and other interbowel diseases, Lupus, myasthenia gravis, myocardial or pericardial inflammation, pancreatitis, polymyositis, psoriasis, Reiter's syndrome, scleroderma, systemic analphylaxis, ulcerative colitis, nephritis (including glomerulonephritis), gout, arthritis (such as rheumatoid arthritis and osteoarthritis), erythema, dermatitis, dermatomyositis, bronchitis, cholecystitis, sepsis and gastritis.

Without being limited by theory, the compounds of the present invention exhibit selective inhibition of JAK1 with respect to JAK 2, JAK 3 and TYK 2. Therefore, it is submitted that the compounds of the present invention demonstrate selective inhibition and therefore are more specific and advantageous than other compounds in prior art, as they are expected to result in less adverse effects.

The examples and scheme below depict the general synthetic procedure for the compounds disclosed herein. Synthesis of the compounds of Formulae I disclosed herein, and embodiments thereof, are not limited by these examples and schemes. One skilled in the art will know that other procedures can be used to synthesize the compounds of Formulae I disclosed herein, and that the procedures described in the examples and schemes is only one such procedure. In the descriptions below, one of ordinary skill in the art would recognize that specific reaction conditions, added reagents, solvents, and reaction temperatures can be modified for the

synthesis of specific compounds that fall within the scope of this disclosure. All intermediate compounds described below, for which there is no description of how to synthesize such intermediates within these examples below, are commercially available compounds unless otherwise specified.

Synthesis of Compound no. _1177: 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)acetonitrile

Step-1: Synthesis of tert-butyl 3-hydroxypyrrolidine-1-carboxylate:

To a stirred solution solution of tert-butyl 3-oxopyrrolidine-1-carboxylate (0.50 g, 2.699 mmol) in ethanol (5 mL) was added sodium borohydride (0.20 g, 5.399 mmol) at 0⁰C and the mixture was stirred at room temperature for 4h. Progress of reaction was monitored by TLC. After reaction completion water (10 mL) was added to the reaction mixture and the product extracted with ethyl acetate. The organic layer was dried over sodium sulphate, concentrated under reduced pressure to give tert-butyl 3-hydroxypyrrolidine-1-carboxylate (0.5 g, 99%) as yellow solid.

MS: 188.24 [M+1]

Step-2: Synthesis of 1-(tert-butoxycarbonyl)pyrrolidin-3-yl methanesulfonate

To a stirred solution of tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.0 g, 5.347 mmol) in DCM (10.0 mL) at 0⁰C was added MsCl (0.673 g, 5.882 mmol) under nitrogen. To resultant reaction mixture DIPEA (0.898 g, 6.951 mmol) solution in DCM (1.0 mL) was added drop wise, stirred for 4h at RT and progress of reaction was monitored by TLC. On completion, quenched with water, extracted with ethyl acetate. Organic layer was dried over sodium sulphate, concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 10% ethyl acetate in hexane as eluent to 1-(tert-butoxycarbonyl)pyrrolidin-3-yl methanesulfonate (0.25 g, 25 %) as crude yellow oily mass. MS: 266.33 [M+1]

Step-3: synthesis of tert-butyl 3-cyanopyrrolidine-1-carboxylate

To a stirred solution of 1-(tert-butoxycarbonyl) pyrrolidin-3-yl methanesulfonate (0.25 g, 0.9432 mmol) in DMF (5 mL) and water (1 mL) was added KCN (0.138 g, 2.830 mmol) under nitrogen and the resulted solution heated overnight at 80⁰C. Progress of reaction was monitored by TLC. After reaction completion reaction mass was cooled to 0⁰C and quenched with water. Product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 6% acetone/hexane as eluent to obtain tert-butyl 3-cyanopyrrolidine-1-carboxylate (0.15 g, 81 %) as yellow oil. MS: 197.25 [M+1]

Step-4: synthesis of pyrrolidine-3-carbonitrile trifluoroacetate

To a stirred solution of tert-butyl 3-cyanopyrrolidine-1-carboxylate (0.15 g, 0.765 mmol) in DCM (5 mL) was added TFA (0.8 mL) at 0⁰C and reaction allowed to stir at room temperature for 4h. Reaction was monitored by TLC. On completion all volatiles were evaporated under reduced pressure, residue was triturated with diethtyl ether, filtered and dried to obtained pyrrolidine-3-carbonitrile trifluoroacetate (0.1 g, 62.2 %) as off brown solid.

MS: 194.15 [M+1]

Step-5: synthesis of 4-nitrophenyl 3-cyanocyclopentanecarboxylate

To a stirred solution of pyrrolidine-3-carbonitrile trifluoroacetate (0.05 g, 0.238 mmol) in ACN (5.0 mL), trimethylamine (0.072 g , 0.714 mmol) was added followed by 4-nitrophenyl chloroformate (0.047 g , 0.238 mmol) at 00C. The resultant reaction mixture was stirred for 4h at room temperature. Completion of reaction was monitored by TLC. On completion product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give 4-nitrophenyl 3-cyanocyclopentanecarboxylate (0.05 g, 80.5%) as white solid

MS: 261.25 [M+1]

Step-6: synthesis of 1-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile

To a stirred solution of 3-nitro-4-(1H-pyrazol-4-yl)pyridin-2-amine (0.05 g, 0.2439 mmol) in DMF (2 mL) at 0⁰C was added NaH (0.02 g, 0.4878 mmol) under nitrogen and stirred for 30 min. at same temperature. To resultant reaction mass solution of 4-nitrophenyl 3-cyanocyclopentanecarboxylate (0.094 g, 0.7894 mmol) in DMF was added at 0⁰C and stirred

for 4h at RT. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 0.5 % Methanol in DCM as eluent to obtain 1-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile (0.03 g, 37.6 %) as yellow solid.

MS: 328.3 [M+1]

Step-7: Synthesis of 1-(4-(2,3-diaminopyridin-4-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile

15 16

To a stirred solution of 1-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile (0.03 g, 0.0917 mmol) in methanol (5 mL) was hydrogenated by 10% Pd/C (0.003 g, 10 % wt/wt) using hydrogen balloon. Progress of the reaction was monitored by TLC. After reaction completion reaction mass filtered through celite and filtrate was evaporated under reduced pressure to give 2-(6-(4-(2,3-diaminopyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)acetonitrile (0.02 g, 73.5 %) as brown solid.

MS: 298.3 [M+1]

Step-8: Synthesis of 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile

Trimethyl orthoformate

THF, PTSA, 70°C, 4h

17 1177

To a stirred solution of 2-(6-(4-(2,3-diaminopyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)acetonitrile (0.025 g, 0.0841 mmol) in trimethyl orthoformate (1.0 mL) was added. To resultant reaction mixture, PTSA (0.004 g) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, quenched with aq. sodium bicarbonate solution, extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 3% to 5% MeOH in DCM to obtain 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3-carbonitrile (0.01 g, 40 %) as off white solid.

MS: 308.3 [M+1]

Synthesis of Compound No: 1056: N-(3-cyanocyclobutyl)-4- (2,3-dihydro-2-oxo-1H-imidazo [4,5-b] pyridin-7-yl) -1H-pyrazole-1- carboxamide

Step-1: Synthesis of tert-butyl 3-carbamoylcyclobutylcarbamate:

18 19

To a stirred solution of tert-butyl 3-cyanopyrrolidine-1-carboxylate (0.500 g, 2.325 mmol) in THF (15 mL) was added ethyl chloroformate (0.301 mg, 2.79mmol) at 0⁰C and reaction allowed to stir at room temperature for 1h. To resultant reaction mass solution of ammonium hydroxide ( 5.0 mL) was added at 0⁰C and stirred for 4h at RT. Reaction was monitored by TLC. On completion product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give to obtained tert-butyl 3-carbamoylcyclobutylcarbamate (0.430 g, 85.65 %) as colourless liquid.

MS: 215.12 [M+1]

Step-2: Synthesis of tert-butyl 3-cyanocyclobutylcarbamate:

To a stirred solution of tert-butyl 3-carbamoylcyclobutylcarbamate (0.400 g, 1.869 mmol) in pyridine (5.0 mL) was added POCl3 (1.84g, 1.200 mmol) at 0⁰C and reaction allowed to stir at room temperature for 1h. Reaction was monitored by TLC. On completion product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give to obtained tert-butyl 3-cyanocyclobutylcarbamate (0.340 g, 98.8 %) as colourless liquid.

MS: 197.15 [M+1]

Step-3: Synthesis of 3-aminocyclobutanecarbonitrile hydrochloride:

To a stirred solution of tert-butyl 3-cyanocyclobutylcarbamate (0.300 g, 1.522 mmol) in DCM (5 mL) was added Dioxane-HCl (2.5 mL) at 0⁰C and reaction allowed to stir at room temperature for 4h. Reaction was monitored by TLC. On completion all volatiles were evaporated under reduced pressure, residue was triturated with di-ethyl ether, filtered and dried to obtained 3-aminocyclobutanecarbonitrile hydrochloride (0.240 g, 94.63 %) as off white solid.

MS: 133.05 [M+1]

Step-4: synthesis of 4-nitrophenyl 3-cyanocyclobutylcarbamate

To a stirred solution of 3-aminocyclobutanecarbonitrile hydrochloride (0.300 g, 2.247 mmol) in ACN (5.0 mL), trimethylamine (0.493 g, 4.89 mmol) was added followed by 4-nitrophenyl chloroformate (0.544 g, 2.706 mmol) at 00C. The resultant reaction mixture was stirred for 4h at room temperature. Completion of reaction was monitored by TLC. On completion product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give 4-nitrophenyl 3- cyanocyclobutylcarbamate (0.250 g, 42.23%) as yellowish solid.

MS: 262.05 [M+1]

Step-5: synthesis of N-(3-cyanocyclobutyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5- b]pyridin-7-yl)-1H-pyrazole-1-carboxamide

To a stirred solution of 7-(1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one hydrochloride (0.05 g, 0.210 mmol) in ACN (2.5 mL) at 0⁰C was added TEA (0.053 g, 0.527 mmol) under nitrogen and stirred for 30 min. at same temperature. To resultant reaction mass solution of 4-nitrophenyl 3-cyanocyclobutylcarbamate (0.081 g, 0.315 mmol) in ACN was added at 0⁰C followed by TEA (0.035 g, 0.315 mmol) under nitrogen and stirred for 4h at RT. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 3-5 % Methanol in DCM as eluent to obtain N-(3-cyanocyclobutyl)-4- (2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide (0.03 g, 37.6 %) as off white solid.

MS: 324.11 [M+1]

Synthesis of compound No. 1063: N-(cyano(phenyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide

Step-1: 2-amino-2-phenylacetonitrile

29

To a stirred solution of benzaldehyde (1.0 g, 0.934 mmol) in Ethanol (20 mL) was added ammonium chloride (0.99g, 1.86mmol), ammonium hydroxide (12.5 ml, 25%) and potassium cyanide (078g,1.21mmol) at room temperature. The resultant reaction mixture was stirred at same temperature for 4h. Completion of reaction was monitored by TLC. On completion, quenched with ice water, extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate, concentrated under reduced pressure to obtained 2-amino-2-phenylacetonitrile (0.600g, 48.3%) as orange solid.

MS: 133.04 [M+1]

Step-2 : 4-nitrophenyl cyano(phenyl)methylcarbamate

To a stirred solution of 2-amino-2-phenylacetonitrile (0.200 g, 1.515 mmol) in chloroform (5.0 mL), pyridine (0.3 g , 3.03 mmol) was added followed by 4-nitrophenyl chloroformate (0.3 g , 1.515 mmol) at 00C. The resultant reaction mixture was stirred for 4h at room temperature. Completion of reaction was monitored by TLC. On completion product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give 4-nitrophenyl cyano(phenyl)methylcarbamate (0.200 g, 44.4%) as white solid

MS: 298.25 [M+1]

Step-3: 3 Synthesis of N-(cyano(phenyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide

1063

To a stirred solution of 7-(1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one hydrochloride (0.030g, 0.0127 mmol) in DMF (2.0 mL), trimethylamine (0.038g, 0.0381) and 4-nitrophenyl cyano(phenyl)methylcarbamate (0.037g, 0.0127 mmol) was added. The resultant reaction mixturewas stirred 6h at room temprature. Completion of reaction was monitored by TLC. On completion, quenched with bicarbonate water, extracted with 10% MeOH in DCM. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 8 to 9% MeOH in DCM to obtain N-(cyano(phenyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide (0.004 g, 8.7%) as off white solid.

MS: 360.1[M+1]

Synthesis of Compound No.1064:- N-(2,2,2-trifluoroethyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide

Step-1: Synthesis of 4-(2-amino-3-nitropyridin-4-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide

To a stirred solution of 3-nitro-4-(1H-pyrazol-4-yl)pyridin-2-amine (0.150 g, 0.073 mmol) in acetonitrile (10 mL) and trimethylamine(0.147g, 0.146mmol), was added 4-nitrophenyl 2,2,2-trifluoroethylcarbamate (0.231g, 0.087 mmol) at room temperature. The resultant reaction mixture was stirred at 600C temperature for 6h. Completion of reaction was monitored by TLC. On completion, quenched with ice water, extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate, concentrated under reduced pressure obtained crude reaction mass. Purification of the crude was done via silica gel (100-200 Mesh) column chromatography and desired compound eluted at 3 to 4% methanol in DCM to obtained 4-(2-amino-3-nitropyridin-4-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide (0.160g, 67%) as yellow solid.

MS: 331.04 [M+1]

Step-2: Synthesis of 4-(2,3-diaminopyridin-4-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide

To a stirred solution of 4-(2-amino-3-nitropyridin-4-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide (0.080g, 0.024 mmol) in EtOH (3.0 mL), NH4Cl (2.0 mL) was added at room temperature. To resultant reaction mixture, Fe powder (0.064 g, 0.12 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, reaction mixture was diluted with H2O: EtOAc (50 mL, 5:5) and pass over celite to remove inorganic impurities from the reaction mixture. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to obtained 4-(2,3-diaminopyridin-4-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide (0.045 g, 62.5 %) as dark brown solid mass.

MS: 301.2 [M+1]

Step-: 3 Synthesis of N-(2,2,2-trifluoroethyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide

To a stirred solution of 4-(2,3-diaminopyridin-4-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carboxamide (0.045g, 0.015 mmol) in THF (1.0 mL), trimethyl orthoformate (2.0 mL) was added. To resultant reaction mixture, PTSA (0.0051 g, 0.0030 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, quenched with

bicarbonate water, extracted with 10% MeOH in DCM. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 8 to 9% MeOH in DCM to obtained N-(2,2,2-trifluoroethyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide (0.023 g, 50%) as off white solid.

MS: 311.1[M+1]

Synthesis of Compound No.1119: 7-(1-(5-(2,2,2-trifluoro-1-methoxy ethyl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

Step-1: Synthesis of 6-bromopyridine-3-carbaldehyde:

To a stirred solution of 2,5-dibromopyridine (26.0 g, 109.75 mmol) in diethyl ether (500 mL) at -78⁰C was added n-Butyl lithium (2.5M in hexane) (66 mL, 164.63 mmol) under nitrogen and stirred for 1h at same temperature. DMF (13 mL, 164.63 mmol) was then added drop wise to the reaction mixture, stirred for 1h at -78⁰C. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with diethyl ether. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 4% ethyl acetate in hexane as eluent to obtain 6-bromopyridine-3-carbaldehyde (12.20 g, 59.8 %) as yellow oil.

MS: 187.0 [M+1]

Step-2: Synthesis of 1-(6-bromopyridin-3-yl)-2,2,2-trifluoroethanol

To a stirred solution of 6-bromopyridine-3-carbaldehyde (2.0 g, 10.75mmol) in DME (50 mL) at 0⁰C was added TMSCF3 (1.61 g, 16.12 mmol) under nitrogen, followed by portion wise addition of CsF (2.44 g, 16.12 mmol) and stirred for 1h at same temperature. Allow to warm to RT and Stirred for 6h. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) on flash column chromatography using 20% ethyl acetate in hexane as eluent to obtain 1-(6-bromopyridin-3-yl)-2,2,2-trifluoroethanol (1.24 g, 47.69 %) as yellow oil.

MS: 257.8 [M+1]

Step-3: synthesis of 2-bromo-5-(2,2,2-trifluoro-1-methoxyethyl)pyridine

To a stirred solution of 1-(6-bromopyridin-3-yl)-2,2,2-trifluoroethanol (0.40 g, 15.56 mmol) in THF (5.0 mL) at 0⁰C was added NaH (0.081 g, 20.23 mmol) under nitrogen and stirred for 1h at same temperature. To resultant reaction mass MeI (0.232 g, 20.23mmol) solution in THF (3.0 mL) was added Allow to warm to RT and Stirred for 1h. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 10% acetone in hexane as eluent to obtain 2-bromo-5-(2,2,2-trifluoro-1-methoxyethyl)pyridine (0.39 g, 92.19 %) as colourless oil.

MS: 271.0 [M+1]

Step-4: Synthesis of 4-(1-(5-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-nitropyridin-2-amine

To a stirred solution of 3-nitro-4-(1H-pyrazol-4-yl) pyridin-2-amine (0.15g, 0.73 mmol) and compound 2-bromo-5-(2,2,2-trifluoro-1-methoxyethyl)pyridine (0.278g, 1.02 mmol) in DMSO (5 ml) was added K2CO3 (0.251g, 1.825 mmol) followed by CuI (0.013g, 0.073 mmol) and L-Proline (0.056g, 0.365 mmol). Reaction was heated at 110oC for 16h. Reaction was monitored by TLC. On completion reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 40-60% acetone in n-hexane to obtained 4-(1-(5-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-nitropyridin-2-amine (0.075 g, 37.87 %) as yellow solid.

MS: 394.4[M+1]

Step-5: Synthesis of 4-(1-(5-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)pyridine-2,3-diamine

To a stirred solution of 4-(1-(5-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-nitropyridin-2-amine (0.070g, 1.77 mmol) in EtOH (3.0 mL), NH4Cl (2.5 mL) was added at room temperature. To resultant reaction mixture, Fe powder (0.025 g, 0.45 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, reaction mixture was diluted with H2O: EtOAc (50 mL, 5:5) and pass over celite to remove inorganic impurities from the reaction mixture. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to obtained pure 4-(1-(5-(2,2,2- trifluoro-1- methoxy ethyl) pyridin-2-yl)-1H-pyrazol-4-yl) pyridine -2,3-diamine (0.035g, 53.03%) as dark brown solid mass.

MS: 364.2 [M+1]

Step-6: Synthesis of 7-(1-(5-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

53 1119

To a stirred solution of 4-(1-(5-(2,2,2-trifluoro-1- methoxy ethyl) pyridin-2-yl)-1H-pyrazol-4-yl) pyridine -2,3-diamine (0.035g, 0.093 mmol) in THF (1.0 mL), Trimethyl orthoformate (1.5 mL) was added. To resultant reaction mixture, PTSA (0.002 g, 0.018 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, quenched with bicarbonate water, extracted with 10% MeOH in DCM. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 3% to 5% MeOH in DCM to obtained 7-(1-(5-(2,2,2- trifluoro-1-methoxy ethyl)pyridin-2-yl)-1H-pyrazol-4-yl) -3H-imidazo [4,5-b] pyridine (0.07 g, 19.44%) as off white solid.

MS: 375.9[M+1]

Synthesis of Compound No.1126: 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol

Step-1: Synthesis of N-methoxy-N-methyl cyclopropane carboxamide:

To a stirred solution of cyclopropane carbonyl chloride (10.0 g, 961.5 mmol) and N-methoxy methanamine hydrochloride (11.20 g, 1153.8 mmol) in THF (150 mL), TEA (24.20g, 2403.8 mmol) was added drop-wise at 0°C and allow to stirred for 30 min. Resultant reaction mass was then placed at RT and stirred for 4h. Completion of reaction was monitored by TLC. On completion, concentrated under reduced pressure to obtained crude mass. Purification of the crude was done via silica gel (100-200 Mesh) column chromatography and desired compound eluted at 5% ether/n-Hexane to obtained N-methoxy-N-methyl cyclopropane carboxamide (7.45g, 60%) as colourless oily mass.

MS: 130.07 [M+1]

Step-2: Synthesis of (6-bromopyridin-3-yl)(cyclopropyl)methanone:

To a stirred solution of 2,5-dibromopyridine (12.0 g, 50.63mmol) in diethyl ether (250 mL) at -78⁰C was added n-Butyl lithium (2.5M in hexane) (24.30 mL, 65.81mmol) under nitrogen and stirred for 1h at same temperature. N-methoxy-N-methyl cyclopropane carboxamide (7.1 g, 55.69 mmol) was then added drop wise to the reaction mixture, stirred for 1h at -78⁰C. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with diethyl ether. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 4% ethyl acetate in hexane as eluent to obtain (6-bromopyridin-3-yl) (cyclopropyl)methanone (6.46 g, 68.07 %) as yellow oil.

MS: 227.1 [M+1]

Step-3: Synthesis of 1-(6-bromopyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol

To a stirred solution of (6-bromopyridin-3-yl) (cyclopropyl) methanone (2.0 g, 88.49mmol) in DME (25 mL) at 0⁰C was added TMSCF3 (1.86 g, 132.74 mmol) under nitrogen, followed by portion wise addition of CsF (2.01 g, 132.74 mmol) and stirred for 1h at same temperature. Allow to warm to RT and Stirred for 6h. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) on flash column chromatography using 15-20% ethyl acetate in hexane as eluent to obtain 1-(6-bromopyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (1.45 g, 55.76 %) as yellow oil.

MS: 297.4 [M+1]

Step-4: Synthesis of 1-(6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol

To a stirred solution of 3-nitro-4-(1H-pyrazol-4-yl) pyridin-2-amine (0.15g, 0.73 mmol) and compound 1-(6-bromopyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.320g, 1.02 mmol) in DMSO (5 ml) was added K2CO3 (0.251g, 1.825 mmol) followed by CuI (0.013g, 0.073 mmol) and L-Proline (0.056g, 0.365 mmol). Reaction was heated at 110oC for 12h. Reaction was monitored by TLC. On completion reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 40-60% acetone in n-hexane to obtained 1-(6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.065 g, 21.10 %) as yellow solid.

MS: 421.37 [M+1]

Step-5: Synthesis of 1-(6-(4-(2,3-diaminopyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol

To a stirred solution of 1-(6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl) pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.065g, 1.54 mmol) in EtOH (3.0 mL), NH4Cl (2.5 mL) was added at room temperature. To resultant reaction mixture, Fe powder (0.043 g, 7.8 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, reaction mixture was diluted with H2O: EtOAc (50 mL, 5:5) and pass over celite to remove inorganic impurities from the reaction mixture. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to obtained 1-(6-(4-(2,3-diamino pyridin -4-yl)-1H-pyrazol-1-yl )pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.035 g, 57.37 %) as dark brown solid mass.

MS: 391.2 [M+1]

Step-6: Synthesis of 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol

To a stirred solution of 1-(6-(4-(2,3-diamino pyridin -4-yl)-1H- pyrazol-1-yl) pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.035g, 0.089 mmol) in THF (1.0 mL), Trimethyl orthoformate (1.5 mL) was added. To resultant reaction mixture, PTSA (0.003 g, 0.0017 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, quenched with bicarbonate water and extracted with 10% MeOH in DCM. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 3% to 5% MeOH in DCM to obtained 7-(1-(5-(2,2,2-trifluoro-1-methoxy ethyl)pyridin-2-yl)-1H-pyrazol-4-yl) -3H-imidazo [4,5-b] pyridine (0.06 g, 17.19%) as off white solid.

MS: 400.9[M+1]

Synthesis of Compound No. 1128: 7-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

Step-1: Synthesis of 1-(6-bromopyridin-3-yl)ethanone:

To a stirred solution of 2,5-dibromopyridine (12.0 g, 50.63mmol) in diethyl ether (250 mL) at -78⁰C was added n-Butyl lithium (2.5M in hexane) (24.30 mL, 65.81mmol) under nitrogen and stirred for 1h at same temperature. DMA (7.89 g, 60.75 mmol) was then added drop wise to the reaction mixture, stirred for 1h at -78⁰C. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with diethyl ether. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 4% ethyl acetate in hexane as eluent to obtain 1-(6-bromopyridin-3-yl)ethanone (4.5 g, 44.03 %) as yellow oil.

MS: 201.1 [M+1]

Step-2: Synthesis of 2-(6-bromopyridin-3-yl)-1,1,1-trifluoropropan-2-ol

To a stirred solution of 1-(6-bromopyridin-3-yl)ethanone (2.0 g, 11.00mmol) in DME (50 mL) at 0⁰C was added TMSCF3 (2.33 g, 14.30 mmol) under nitrogen, followed by portion wise addition of CsF (2.50 g, 16.50 mmol) and stirred for 1h at same temperature. Allow to warm to RT and Stirred for 6h. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) on flash column chromatography using 15-20% ethyl acetate in hexane as eluent to obtain 2-(6-bromopyridin-3-yl)-1,1,1-trifluoropropan-2-ol (1.45 g, 53.50 %) as yellow oil.

MS: 271.0 [M+1]

Step-3: Synthesis of 2-bromo-5-(1,1,1,2-tetrafluoropropan-2-yl)pyridine

To a stirred solution of 2-(6-bromopyridin-3-yl)-1,1,1-trifluoropropan-2-ol (1.45 g, 53.70mmol) in DCE (35 mL) at 0⁰C was added DAST (1.12 g, 69.81 mmol) under nitrogen, followed by stirred for 15 min at same temperature. Allow to warm to RT and Stirred for 1h. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) on flash column chromatography using 15-20% ethyl acetate in hexane as eluent to obtain 2-bromo-5-(1,1,1,2-tetrafluoropropan-2-yl)pyridine (1.1 g, 75.86 %) as yellow oil.

MS: 273.04 [M+1]

Step-4: Synthesis of 4-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-nitropyridin-2-amine

To a stirred solution of 3-nitro-4-(1H-pyrazol-4-yl) pyridin-2-amine (0.15g, 0.73 mmol) and compound 2-bromo-5-(1,1,1,2-tetrafluoropropan-2-yl)pyridine (0.298g, 1.09 mmol) in DMSO (5 ml) was added K2CO3 (0.251g, 1.825 mmol) followed by CuI (0.013g, 0.073 mmol) and L-Proline (0.056g, 0.365 mmol). Reaction was heated at 110oC for 16h. Reaction was monitored by TLC. On completion reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography, eluent at 40-60% acetone in n-hexane to obtained 4-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-nitropyridin-2-amine (0.065 g, 22.49 %) as yellow solid.

MS: 397.1 [M+1]

Step-5: Synthesis of 4-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)pyridine-2,3-diamine

To a stirred solution of 4-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-nitropyridin-2-amine (0.065g, 0.16 mmol) in EtOH (3.0 mL), NH4Cl (2.5 mL) was added at room temperature. To resultant reaction mixture, Fe powder (0.041 g, 0.82 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, reaction mixture was diluted with H2O: EtOAc (50 mL, 5:5) and pass over celite to remove inorganic impurities from the reaction mixture. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to obtained 4-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)pyridine-2,3-diamine (0.035 g, 58.32 %) as dark brown solid mass.

MS: 367.4 [M+1]

Step-6: Synthesis of 7-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

To a stirred solution of 4-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)pyridine-2,3-diamine (0.035g, 0.095 mmol) in THF (1.0 mL), Trimethyl orthoformate (1.5 mL) was added. To resultant reaction mixture, PTSA (0.003 g, 0.0017 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, quenched with bicarbonate water, extracted with 10% MeOH in DCM. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 3% to 5% MeOH in DCM to obtained 7-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (0.06 g, 16.67%) as off white solid.

MS: 377.2 [M+1]

Synthesis of Compound No. 1164: (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanol

Step-1: Synthesis of N-methoxy-N-methyl cyclopropane carboxamide:

To a stirred solution of 1-(tert-butoxy carbonyl)piperidine-4-carboxylic acid (10.0 g, 43.66 mmol) and N-methoxy methanamine hydrochloride (5.56 g, 56.76 mmol) in DMF (35 mL), DCC (13.51g, 65.49 mmol) and DMAP (1.60g, 13.98 mmol) was added successively at 0°C and allow to stirred for 30 min. Resultant reaction mass was allow to warm to RT and stirred for 4h. Completion of reaction was monitored by TLC. On completion, quenched reaction mixture with 1N HCl water and extracted with EtOAc. The organic layer was washed with bicarbonate water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 20% acetone in n-hexane to obtained tert-butyl 4-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate (7.45g, 60%) as colourless oily mass.

MS: 273.1 [M+1]

Step-2: Synthesis of tert-butyl 4-(6-bromonicotinoyl)piperidine-1-carboxylate

To a stirred solution of 2,5-dibromopyridine (5.0 g, 21.18 mmol) in diethyl ether (100 mL) at -78⁰C was added n-Butyl lithium (2.5M in hexane) (8.47 mL, 21.18 mmol) under nitrogen and stirred for 1h at same temperature. tert-butyl 4-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate (6.36 g, 23.29 mmol) was then added drop wise to the reaction mixture, stirred for 1h at -78⁰C. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with 10% MeOH in DCM. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to obtained tert-butyl 4-(6-bromonicotinoyl)piperidine-1-carboxylate (5.8 g, 67.12%) as colourless oily mass.

MS: 371.0 [M+1]

Step-3: Synthesis of (6-bromopyridin-3-yl)(piperidin-4-yl)methanone:

To a stirred solution of tert-butyl 4-(6-bromonicotinoyl)piperidine-1-carboxylate (5.0 g, 13.51 mmol) in THF (50 mL), 4M HCl in Dioxane (25 mL) was added at 0⁰C under nitrogen. Allow to warm reaction mixture to RT and stirred for 10h. On completion, reaction mixture quenched with bicarbonate solution and extracted with 10% MeOH in DCM. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 4-5% MeOH in DCM as eluent to obtain (6-bromopyridin-3-yl)(piperidin-4-yl)methanone (3.45g, 94.52%) as colourless crystalline solid.

MS: 271.0 [M+1]

Step-4: Synthesis of (6-bromopyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone

To a stirred solution of (6-bromopyridin-3-yl)(piperidin-4-yl)methanone (2.0 g, 7.44mmol) in dry DCM (20 mL) at 0⁰C was added MsCl (1.11 g, 9.66 mmol) under nitrogen. To resultant reaction mixture TEA (1.12 g, 11.16 mmol) was added drop wise to the reaction mixture, stirred for 1h at 0⁰C. Allow to warm to RT and Stirred for 1h. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) on flash column chromatography using 2-3% ethyl MeOH in DCM as eluent to obtain (6-bromopyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone (1.40 g, 56.00 %) as off white solid.

MS: 349.01 [M+1]

Step-5: Synthesis of (6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone

To a stirred solution of 3-nitro-4-(1H-pyrazol-4-yl) pyridin-2-amine (0.15g, 0.73 mmol) and compound (6-bromopyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone (0.254g,

mmol) in DMA (5 ml) was added K2CO3 (0.251g, 1.825 mmol). Reaction was heated at 110oC for 6h. Reaction was monitored by TLC. On completion reaction mixture was quenched with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) on flash column chromatography using 4-5% MeOH in DCM as eluent to obtained (6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone (0.065 g, 18.84 %) as yellow solid.

MS: 472.02 [M+1]

Step-6: Synthesis of 1-(6-(4-(2,3-diaminopyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol

To a stirred solution of 1-(6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.065g, 1.37 mmol) in EtOH (3.0 mL), NH4Cl (2.5 mL) was added at room temperature. To resultant reaction mixture, Fe powder (0.037 g, 6.8 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, reaction mixture was diluted with H2O: EtOAc (50 mL, 5:5) and pass over celite to remove inorganic impurities from the reaction mixture. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to obtained 1-(6-(4-(2,3-diamino pyridin -4-yl)-1H-pyrazol-1-yl )pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.035 g, 57.37 %) as dark brown solid mass.

MS: 442.0 [M+1]

Step-7: Synthesis of (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone

To a stirred solution of 1-(6-(4-(2,3-diamino pyridin -4-yl)-1H- pyrazol-1-yl )pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol (0.035g, 7.93 mmol) in THF (1.0 mL), trimethyl orthoformate (1.5 mL) was added. To resultant reaction mixture, PTSA (0.003 g, 0.0017 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, quenched with bicarbonate water, extracted with 10% MeOH in DCM. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) on flash column chromatography using 5-6% MeOH in DCM as eluent to obtained (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone (0.006 g, 17.41%) as off white solid.

MS: 452.0 [M+1]

Step-8: Synthesis of 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethanol

To a stirred solution of (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanone (0.006g, 0.013 mmol) in THF (1.0 mL), NaBH4 (0.001 g, 0.026 mmol) was added and stirred for 2h at 0°C. Completion of reaction was monitored by TLC. On completion, quenched with water, extracted with 10% MeOH in DCM. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to obtained (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1-(methylsulfonyl)piperidin-4-yl)methanol (0.03 g, 50.00%) as off white solid.

MS: 454.0 [M+1]

Synthesis of Compound No.1166: 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1-dioxidothiomorpholino)acetonitrile

Step-1: Synthesis of 6-bromopyridine-3-carbaldehyde:

To a stirred solution of 2,5-dibromopyridine (26.0 g, 109.75 mmol) in diethyl ether (500 mL) at -78⁰C was added n-Butyl lithium (2.5M in hexane) (66 mL, 164.63 mmol) under nitrogen and stirred for 1h at same temperature. DMF (13 mL, 164.63 mmol) was then added drop wise to the reaction mixture, stirred for 1h at -78⁰C. Progress of reaction was monitored by TLC. After reaction completion reaction mass was quenched with ice cold water. Phases separated and aqueous layer was extracted with diethyl ether. The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 4% ethyl acetate in hexane as eluent to obtain 6-bromopyridine-3-carbaldehyde (12.20 g, 59.8 %) as yellow oil.

MS: 187.0 [M+1]

Step-2: Synthesis of 6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl) pyridine-3-carbaldehyde

To a stirred solution of 3-nitro-4-(1H-pyrazol-4-yl) pyridin-2-amine (0.075g, 0.36 mmol) and compound 6-bromopyridine-3-carbaldehyde (0.075g, 0.40 mmol) in DMA (5 ml) was added K2CO3 (0.124g, 0.90 mmol) and reaction heated at 110oC for 16h. Reaction was monitored by TLC. On completion reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to give crude desired product that was purified by silica gel (100 to 200 Mesh) column chromatography: eluent at 1% to 3% MeOH/DCM to obtained 6-(4-(2-amino-3- nitropyridin-4-yl) -1H-pyrazol-1-yl) pyridine-3-carbaldehyde (0.065 g, 51.58%) as yellow solid.

MS: 311[M+1]

Step-3: 2-(6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1-dioxidothiomorpholino)acetonitrile

To a stirred solution of 6-(4-(2-amino-3- nitropyridin-4-yl) -1H-pyrazol-1-yl) pyridine-3-carbaldehyde (0.065g, 0.20 mmol) in AcOH (5mL) , Trimethyl silylcynide (TMSCN) (0.031g, 0.31 mmol) and TMSCN (0.051g, 0.38 mmol) in AcOH (1 mL) was added at 0°C and allow to warm to RT. Stirred for 16h. Reaction was monitored by TLC. On completion reaction mixture was quenched with bi-carbonate water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 2-3% MeOH in DCM as eluent to obtain obtained 2-(6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1-dioxidothiomorpholino)acetonitrile (0.045 g, 47.36%) as yellow solid.

MS: 454 [M+1]

Step-4: 2-(6-(4- diaminopyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1-
dioxidothiomorpholino)acetonitrile

To a stirred solution of 2-(6-(4-(2-amino-3-nitropyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1-dioxidothiomorpholino)acetonitrile (0.045g, 0.09 mmol) in EtOH (10 mL), NH4Cl (2.5 mL) was added at room temperature. To resultant reaction mixture, Fe powder (0.027 g, 0.49 mmol) was added and stirred for 4h at 70°C. Completion of reaction was monitored by TLC. On completion, reaction mixture was diluted with H2O: EtOAc 5:5 (50 mL) and pass over celite to remove inorganic impurities from the reaction mixture. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated under reduced pressure to obtained pure 2-(6-(4-(2,3-diaminopyridin-4-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1-dioxidothiomorpholino)acetonitrile (0.016g, 37.20%) as dark brown solid mass.

We Claim:

1. 1H-imidazo[4,5-b]pyridin-2(3H)-one as selective inhibitor of JAK 1 their pharmaceutically acceptable salts and isomers of formula I:

Wherein;

A is a 5 membered or a 6 membered carbocycle or heterocycle comprising 1 to 3 heteroatom selected from the group comprising O, N, S optionally substituted with CH3, F or Cl;

B is H or alkoxy or O, -CO-, optionally substituted 3 to 8 carbocyclic ring, 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S;

X is independently, H, (CH2)n, -CO-, OCO, COO; CO(CH2)n, (NH2)n; (CH2)n(NH2)n; (CH2)n(NH2)nCN; CONH; CONR1R2, CO(NH2)n; (CH2)nCO(NH2)n, CO(NH2)n(CH2)CF3, SO2(CH2)n, NH(CH2)nCN, unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S and SO2, and substituents on the carboxylic or heterocyclic ring may be selected from Halogen, Alkoxy, CHMe, -CH(CF3), - C(CF3)(OH), C(CF3)(OMe), -CH(CN), CHOH, CH(R5),

Y may be absent or may be selected from H, R1, R2, halo, , C1-C6 Alkyl, C1-C6 Alkoxy CN, -CO-, COR1, (CH2)n, -(CH2)nCN -, CH2CF3, COOH, OR1, NR1R2, -COOR1, - CON(R1)2,-SO2(CH2)n,-SO2N(R1)2, -OCOR1, CONHCH(CH3)-CF3, CH2CN, CH2SO2CH3 -NR1COR1, -CONH, CONR1R2, -CO(NH2)n(CH2)nSO2; - CONH(CH2)nOH, CONH(CH2)nSO2R1R2, -CONH-(CH2)nCF3, -CONH(CH2)nCF3,- NHCONH(CH2)nCF3, NHCONHR1, -NHCOR1R2, NR1CONR1R2, (NH2)n, -NH2CH2,

NH2CH2CF3,-CH(CF3)-(CH)n-CO-N-R1R2,CH(CF3)-(CH)n-SO2,

(CH)n;CH(OH)(CF3)(Heretocycle)R1, optionally substituted 3 to 8 membered carbocyclic ring, or 3 to 8 membered saturated, mono-, fused- or bridged heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, optionally substituted 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, wherein the substitution may independently be R1 and R2 at any position of the ring;C1-6alk-aryl, ArC1-6alkyl;

R1 and R2 are independently selected from the group comprising H, halo, CN, CF3, hydroxyl, Amino, SO2, SO2, C1-C6 Alkyl, SO2-C3-C8-cycloalkyl, CH2CN, CH2CF3, unsubstituted or substituted C1-C6 straight or branched alkyl wherein the substituents are selected from halo, OH, CN, C1-C6 alkoxy, optionally substituted NH2, C1-C6 alkylsulfonyl, optionally substituted CONH2, unsubstituted or substituted C3-C8 carbocyclyl or 3-8 membered heterocyclic ring with 1-3 heteroatoms selected from O, N and S, SO2, C1-C6 straight or branched alkenyl, C1-C6 straight or branched alkynyl, , C1-C6 alkyloxy; C1-C6 alkylamino, C1-C6 alkylcarbonyl, C(O)-C3-C8-cycloalkyl, heteroalkyl, optionally substituted CONH2, C3–C8 cycloalkyl, C3–C8cycloalkenyl, C3– C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl, - CH(CF3)-(CH)n-CO-N-R3R4, -CH(CF3)-(CH)n-SO2-NR3R4, CH(CF3)-(CH)n-NR3R4, CH(CF3)-NR3R4, CH(CF3)-(CH)n-SO2-CHR3R4, wherein cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, carbocyclyl, aryl and heteroaryl groups are optionally substituted;

R3 and R4 are H, independently CH3, C3–C8 cycloalkyl;

R5 is unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S, SO2;

R6, is independently H, C1-C6 straight or branched alkyl, halogen;

X can be connected to Y at any atom so as to arrive at chemically viable bond;

n is 0 to 3.

2. The compounds of formula I, as claimed in claim 1, selected from the group comprising:

1001. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)benzamide;

1002. 1-(1,1,1-trifluoropropan-2-yl)-3-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin- 7-yl)phenyl)urea;

1003. 1-(2,2,2-trifluoroethyl)-3-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)phenyl)urea;

1004. 1-(2,2,2-trifluoroethyl)-3-(5-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)pyrimidin-2-yl)urea;

1005. 1-(2,2,2-trifluoroethyl)-3-(5-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)pyridin-2-yl)urea;

1006. 1-(5-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)pyrazin-2-yl)-3-(2,2,2- trifluoroethyl)urea;

1007. N-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)-3,3- dimethylazetidine-1-carboxamide;

1008. N-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)morpholine-4- carboxamide;

1009. 1-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)phenyl)-3-(pyridin-4- yl)urea;

1010. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)phenyl)-3-(2,2,2-trifluoroethyl)urea;

1011. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)piperazine-1-carboxamide;

1012. N-(cyanomethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)piperazine-1-carboxamide;

1013. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2- (methylsulfonyl)ethyl)piperazine-1-carboxamide;

1014. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(pyridin-4-yl)piperazine- 1-carboxamide;

1015. N-(2-fluoropyridin-4-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)piperazine-1-carboxamide;

1016. N-(1-(methylsulfonyl)piperidin-4-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5- b]pyridin-7-yl)piperazine-1-carboxamide;

1017. N-(cyclopentylmethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)piperazine-1-carboxamide;

1018. 7-(4-(1,1-dioxidothiomorpholine-4-carbonyl)piperazin-1-yl)-1,3-dihydro-2H- imidazo[4,5-b]pyridin-2-one;

1019. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2-methoxypyridin-4- yl)piperazine-1-carboxamide;

1020. N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4-(2-oxo-2,3-dihydro-1H- imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxamide;

1021. N-(1,1,1-trifluoropropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)piperazine-1-carboxamide;

1022. N-(2,2,2-trifluoroethyl)-4-(2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl)piperazine-1- carboxamide;

1023. 7-(4-(3,3-dimethylazetidine-1-carbonyl)piperazin-1-yl)-1,3-dihydro-2H- imidazo[4,5-b]pyridin-2-one;

1024. 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2-methyl-4- (methylsulfonyl)phenyl)piperazine-1-carboxamide;

1025. N-(2,2,2-trifluoroethyl)-2-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)piperazin-1-yl)acetamide;

1026. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1027. N-(cyanomethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide;

1028. N-(2,2,2-trifluoroethyl)-3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrrole-1-carboxamide;

1029. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-1-methyl-2-oxo-1H-imidazo[4,5- b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1030. N-(1,1,1-trifluoropropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)-1H-pyrazole-1-carboxamide;

1031. 7-(1-(4,4,4-trifluorobutanoyl)-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)- one;

1032. N-(1-cyanocyclopropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1033. N-(2-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1034. N-(cyclopentylmethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide;

1035. N-(cyanomethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide hydrochloride;

1036. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1037. 7-(1-(3,3-dimethylazetidine-1-carbonyl)-1H-pyrazol-4-yl)-1,3-dihydro-2H- imidazo[4,5-b]pyridin-2-one;

1038. N-(cyano(cyclopentyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)-1H-pyrazole-1-carboxamide;

1039. N-(2-cyano-1-cyclopentylethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin- 7-yl)-1H-pyrazole-1-carboxamide;

1040. N-(2-cyanobutan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide;

1041. N-(1-cyclopentyl-2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5- b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1042. 4-(1-ethyl-2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2- trifluoroethyl)-1H-pyrazole-1-carboxamide;

1043. N-(cyano(cyclopropyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)-1H-pyrazole-1-carboxamide;

1044. N-(1-cyano-2-methylpropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7- yl)-1H-pyrazole-1-carboxamide;

1045. N-(2,2,2-trifluoroethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1046. N-(1-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1047. N-((S)-1-cyano-2-methylpropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin- 7-yl)-1H-pyrazole-1-carboxamide;

1048. 1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carbonyl)azetidine-3-carbonitrile;

1049. N-((R)-1-cyano-2-methylpropyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin- 7-yl)-1H-pyrazole-1-carboxamide;

1050. N-(3-cyano-1,1,1-trifluoropropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5- b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1051. N-(2-cyano-1-cyclopropylethyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin- 7-yl)-1H-pyrazole-1-carboxamide;

1052. N-(1-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1053. N-(1-cyanopropan-2-yl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1054. N-((R)-cyano(cyclopropyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5- b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1055. 1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carbonyl)pyrrolidine-3-carbonitrile;

1056. N-(3-cyanocyclobutyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide;

1057. 2-(1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carbonyl)pyrrolidin-3-yl)acetonitrile;

1058. N-(1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-2,3-dihydro-1H- imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1059. N-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5- b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1060. N-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5- b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1061. 3-(1-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carbonyl)pyrrolidin-3-yl)propanenitrile;

1062. N-(2-cyano-1-(tetrahydro-2H-pyran-4-yl)ethyl)-4-(2,3-dihydro-2-oxo-1H- imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carboxamide;

1063. N-(cyano(phenyl)methyl)-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)- 1H-pyrazole-1-carboxamide;

1064. N-(2,2,2-trifluoroethyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carboxamide;

1065. N-(2-cyano-1-(tetrahydro-2H-pyran-4-yl)ethyl)-4-(3H-imidazo[4,5-b]pyridin-7- yl)-1H-pyrazole-1-carboxamide;

1066. N-(2-cyanocyclohexyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carboxamide;

1067. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)piperidine-4- carbonitrile;

1068. N-(1-(3-cyanoazetidin-1-yl)propan-2-yl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide;

1069. N-(1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidin-3- yl)propane-1-sulfonamide;

1070. N-(cyano(phenyl)methyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carboxamide;

1071. N-(1-cyano-3-methoxypropyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1- carboxamide;

1072. N-(1-cyano-3-(methylsulfonyl)propyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide;

1073. N-((S)-1-cyano-2-methylpropyl)-4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole- 1-carboxamide;

1074. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)-4- methylpyrrolidine-3-carbonitrile;

1075. 2-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)oxazol-4-yl)acetonitrile; 1076. 2-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)thiazol-4- yl)acetonitrile;

1077. 7-(1-((oxazol-5-yl)methyl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1078. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)acetonitrile;

1079. 6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridine-3-carbonitrile; 1080. 7-(1-(5-((methylsulfonyl)methyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridine;

1081. 7-(1-(5-((oxetan-3-yl)methyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridine;

1082. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)acetonitrile hydrochloride;

1083. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methanol; 1084. 7-(1-(5-(2,2,2-trifluoroethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridine;

1085. 7-(1-(5-(morpholinomethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridine;

1086. 4-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)methyl)thiomorpholine 1,1-dioxide;

1087. 1-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)methyl)azetidine-3-carbonitrile;

1088. 6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-N-(cyanomethyl)pyridine- 3-carboxamide;

1089. N-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)methyl)methanesulfonamide;

1090. N-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)methyl)methanesulfonamide;

1091. N-((6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)methyl)- 2-cyanoacetamide;

1092. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-N-(2,2,2- trifluoroethyl)acetamide;

1093. 2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-N- (cyanomethyl)pyrimidine-5-carboxamide;

1094. N-(2,2,2-trifluoroethyl)-4-(2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl)-1H- pyrazole-1-carboxamide;

1095. 4-(2-ethoxy-3H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2-trifluoroethyl)-1H- pyrazole-1-carboxamide;

1096. 4-(2-cyclopropyl-3H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2-trifluoroethyl)-1H- pyrazole-1-carboxamide;

1097. 3-(4-(2-(4-chloro-3-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol- 1-yl)-tetrahydro-2H-pyran-4-carbonitrile;

1098. 4-(2-(1-acetylpiperidin-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)-N-(2,2,2- trifluoroethyl)-1H-pyrazole-1-carboxamide;

1099. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)acetonitrile; 1100. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2- cyclopropylacetonitrile;

1101. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2- morpholinoacetonitrile;

1102. N-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2- cyanoacetamide;

1103. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-3- fluorophenyl)acetonitrile;

1104. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-2- fluorophenyl)acetonitrile;

1105. 2-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)-2- methoxyphenyl)acetonitrile;

1106. 2-(3-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)acetonitrile; 1107. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)propanenitrile;

1108. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)propenamide;

1109. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)cyclopropanecarbonitrile;

1110. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2- cyclopropylacetonitrile;

1111. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(3,3- difluoroazetidin-1-yl)acetonitrile;

1112. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2- morpholinoacetonitrile;

1113. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1,1- dioxidothiomorpholino)acetonitrile;

1114. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1- (methylsulfonyl)azetidin-3-yl)acetonitrile;

1115. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-(1- (methylsulfonyl)azetidin-3-yl)acetonitrile;

1116. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4- (methylsulfonyl)butanenitrile;

1117. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-2- yl)acetonitrile;

1118. 2-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-4- yl)acetonitrile;

1119. 7-(1-(5-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1120. 7-(1-(5-(1-chloro-2,2,2-trifluoroethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1121. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-N,N-dimethylethanamine;

1122. 7-(1-(5-(1,1,1-trifluorobutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridine;

1123. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutanenitrile;

1124. 7-(1-(5-(2,2,2-trifluoro-1-isopropoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1125. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1- trifluoropropan-2-ol;

1126. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1- cyclopropyl-2,2,2-trifluoroethanol;

1127. 7-(1-(5-(1-cyclopropyl-2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridine;

1128. 7-(1-(5-(1,1,1,2-tetrafluoropropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1129. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1- trifluoro-3-methylbutan-2-ol;

1130. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1- cyclohexyl-2,2,2-trifluoroethanol;

1131. 1-(4-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)- 2,2,2-trifluoro-1-hydroxyethyl)piperidin-1-yl)ethenone;

1132. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1- cyclopentyl-2,2,2-trifluoroethanol;

1133. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-methylpiperidin-4-yl)ethanol;

1134. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(tetrahydro-2H-pyran-4-yl)ethanol;

1135. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(piperidin-4-yl)ethan-1-ol;

1136. 7-(1-(5-(2,2,2-trifluoro-1-(oxetan-3-yl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1137. 7-(1-(5-(2,2,2-trifluoro-1-morpholinoethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1138. 7-(1-(5-(1,1,1-trifluoro-3-(methylsulfonyl)propan-2-yl)pyridin-2-yl)-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridine;

1139. 7-(1-(5-(4-(cyclopropylsulfonyl)-1,1,1-trifluorobutan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1140. 7-(1-(5-(1-((methylsulfonyl)methoxy)-2,2,2-trifluoroethyl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1141. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutane-1-sulfonamide;

1142. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutane-1-sulfonamide;

1143. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)methanesulfonamide;

1144. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N,N-dimethylbutanamide;

1145. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutanamide;

1146. 1-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoroethyl)-3-cyclopropylurea;

1147. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

1148. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoro-N-methylpentanamide;

1149. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)cyclopropanecarboxamide;

1150. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-N- cyclopropyl-5,5,5-trifluoropentanamide;

1151. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)cyclopentanecarboxamide;

1152. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutan-1-amine;

1153. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)cyclopropanamine;

1154. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutan-1-ol;

1155. 7-(1-(5-(1,1,1-trifluoro-4-methoxybutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1156. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoropentanenitrile;

1157. 2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoroethoxy)acetonitrile;

1158. 7-(1-(5-(1-(methylsulfonyl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridine;

1159. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3- yl)(cyclopropyl)methanol;

1160. 7-(1-(5-(3-(methylsulfonyl)-1-(oxetan-3-yl)propyl)pyridin-2-yl)-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridine;

1161. 7-(1-(5-(1-methoxy-3-(methylsulfonyl)propyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1162. 7-(1-(5-(1-fluoro-3-(methylsulfonyl)propyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1163. 7-(1-(5-(4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1164. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1- (methylsulfonyl)piperidin-4-yl)methanol;

1165. (6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)(1- methylpiperidin-4-yl)methanol;

1166. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-N-(2,2,2- trifluoroethyl)-2-hydroxyacetamide;

1167. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2- cyclopropyl-N-(2,2,2-trifluoroethyl)acetamide;

1168. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2-cyano- N-(2,2,2-trifluoroethyl)acetamide;

1169. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoroethanol;

1170. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-2-yl)-2,2,2- trifluoroethanol;

1171. 7-(1-(6-(2,2,2-trifluoro-1-methoxyethyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridine;

1172. 1-(2-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-4-yl)-2,2,2- trifluoroethanol;

1173. 1-(5-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-2-yl)-2,2,2- trifluoroethanol;

1174. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridine;

1175. 7-(1-(6-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridine;

1176. 7-(1-(4-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridine;

1177. 1-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazole-1-carbonyl)pyrrolidine-3- carbonitrile;

1178. 1-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoroethyl)-3-cyclopropylurea;

1179. 1-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)-3-cyclopropylurea;

1180. 3-cyclopentyl-3-(4-(2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1- yl)propanenitrile;

1181. 7-(1-(5-((S)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1182. 7-(1-(5-((R)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1183. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1- trifluoropropan-2-ol;

1184. 7-(1-(5-((R)-2,2,2-trifluoro-1-(oxetan-3-yl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridine;

1185. 7-(1-(5-((S)-2,2,2-trifluoro-1-(oxetan-3-yl)ethyl)pyridin-2-yl)-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridine;

1186. 7-(1-(5-(1,1,1-trifluoro-4-(isopropylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridine;

1187. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-(methyl sulfonyl) 1H-pyrazol-1- yl)pyridin-3-yl)-2,2,2-trifluoroethanamine;

1188. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-(cyclopropyl amino sulfonyl) 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1189. 7-(1-(5-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

1190. 7-(1-(4-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)phenyl)-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridine;

1191. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2- (trifluoromethyl)propan-1-ol;

1192. N-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoroethyl)-2-cyanoacetamide;

1193. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoro-2-methylpentan-2-ol;

1194. 7-(1-(5-(3,3,3-trifluoro-2-((methylsulfonyl)methyl)propyl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1195. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)-N-methylcyclopropanamine;

1196. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-2,2-dimethylbutan-1-ol;

1197. N-(2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)- 2,2,2-trifluoroethoxy)ethyl)cyclopropanamine;

1198. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutan-1-amine;

1199. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)cyclohexanamine;

1200. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutan-1-amine;

1201. 7-(1-(5-(1,1,1-trifluoro-4-morpholinobutan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridine;

1202. 1-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)azetidine-3-carbonitrile;

1203. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-isopropylbutan-1-amine;

1204. 7-(1-(5-(4-(cyclopropylmethylsulfonyl)-1,1,1-trifluorobutan-2-yl)pyridin-2-yl)- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1205. 7-(1-(5-(3-(cyclopropylmethylsulfonyl)-1,1,1-trifluoropropan-2-yl)pyridin-2-yl)- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1206. 7-(1-(5-(1,1,1-trifluoro-3-morpholinopropan-2-yl)pyridin-2-yl)-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridine;

1207. (S)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-isopropylbutan-1-amine;

1208. (R)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-isopropylbutan-1-amine;

1209. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-(Methyl sulfonyl)1H-pyrazol-1- yl)pyridin-3-yl)-3,3,3-trifluoropropan-1-amine;

1210. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoro-N-isopropylpentanamide;

1211. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N,N-diisopropylbutan-1-amine;

1212. N-(2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-3,3,3- trifluoropropyl)cyclopropanamine;

1213. (R)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutanamide;

1214. (S)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutanamide;

1215. (S)-4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoro-N-isopropylpentanamide;

1216. 7-(1-(5-((S)-4-(cyclopropylsulfonyl)-1,1,1-trifluorobutan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1217. (S)-3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-N-methylbutan-1-amine,TFA salt;

1218. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-3,3,3- trifluoro-N-isopropylpropan-1-amine;

1219. 7-(1-(5-(1,1,1-trifluoro-4-(4-methylpiperazin-1-yl)butan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1220. (4-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-hydroxyethyl)piperidin-1-yl)(cyclopropyl)methanone;

1221. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1- ethylpiperidin-4-yl)-2,2,2-trifluoroethanol;

1222. 7-(1-(5-(1,1,1-trifluoro-3-(4-methylpiperazin-1-yl)propan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1223. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1- trifluoro-4-(methylsulfonyl)butan-2-ol;

1224. 5-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-6,6,6- trifluorohexan-2-amine,TFA salt;

1225. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol;

1226. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol;

1227. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoro-4-hydroxypentanenitrile;

1228. 2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoroethoxy)-N-methylethanamine;

1229. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1- trifluoro-3-morpholinopropan-2-ol;

1230. 2-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1,1,1- trifluoro-4-morpholinobutan-2-ol;

1231. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-methylazetidin-3-yl)ethanol;

1232. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1- ethylpyrrolidin-3-yl)-2,2,2-trifluoroethanol;

1233. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1- ethylpyrrolidin-3-yl)-2,2,2-trifluoroethanol;

1234. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-methylpyrrolidin-3-yl)ethanol;

1235. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-methylpyrrolidin-3-yl)ethanol;

1236. 1-(3-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)- 2,2,2-trifluoro-1-hydroxyethyl)azetidin-1-yl)ethenone;

1237. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-isopropylazetidin-3-yl)ethanol;

1238. 4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoro-4-hydroxy-N-isopropylpentanamide;

1239. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-1-(1- ethylazetidin-3-yl)-2,2,2-trifluoroethanol;

1240. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-isopropylpiperidin-4-yl)ethanol;

1241. N-(2-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)- 2,2,2-trifluoroethoxy)ethyl)propan-2-amine,TFA salt;

1242. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-(oxetan-3-yl)pyrrolidin-3-yl)ethanol;

1243. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-(oxetan-3-yl)pyrrolidin-3-yl)ethanol;

1244. 7-(1-(5-(2,2,2-trifluoro-1-methoxy-1-(1-methylpiperidin-4-yl)ethyl)pyridin-2-yl)- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1245. 3-(3-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)- 2,2,2-trifluoro-1-hydroxyethyl)azetidin-1-yl)-3-oxopropanenitrile;

1246. 3-(1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-hydroxyethyl)-N-methylazetidine-1-carboxamide;

1247. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)isobutyramide;

1248. N-(3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluorobutyl)-2-cyanoacetamide;

1249. 3-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-4,4,4- trifluoro-1-morpholinobutan-1-one;

1250. 1-(4-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-5,5,5- trifluoropentanoyl)azetidine-3-carbonitrile;

1251. (S)-1-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2,2,2- trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol;

1252. (R)-1-(4-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)phenyl)-2,2,2- trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol.

3. The 1H-imidazo[4,5-b]pyridin-2(3H)-one compounds as claimed in claim 1, their pharmaceutically acceptable salts and isomers of formula II:

Wherein;

B is H;

X is independently, H, (CH2)n, -CO-, OCO, COO; CO(CH2)n, (NH2)n; (CH2)n(NH2)n; (CH2)n(NH2)nCN; CONH; CONR1R2, CO(NH2)n; (CH2)nCO(NH2)n, CO(NH2)n(CH2)CF3, SO2(CH2)n, NH(CH2)nCN, unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S and SO2, and substituents on the carboxylic or heterocyclic ring may be selected from Halogen, Alkoxy, CHMe, -CH(CF3), - C(CF3)(OH), C(CF3)(OMe), -CH(CN), CHOH, CH(R5),

H, R1, R2, halo, , C1-C6 Alkyl, C1-C6 Alkoxy CN, -CO-, COR1, (CH2)n, -(CH2)nCN -, CH2CF3, COOH, OR1, NR1R2, -COOR1, -CON(R1)2,-SO2(CH2)n,-SO2N(R1)2, - OCOR1, CONHCH(CH3)-CF3, CH2CN, CH2SO2CH3 -NR1COR1, -CONH, CONR1R2, -CO(NH2)n(CH2)nSO2; -CONH(CH2)nOH, CONH(CH2)nSO2R1R2, -CONH- (CH2)nCF3, -CONH(CH2)nCF3,-NHCONH(CH2)nCF3, NHCONHR1, -NHCOR1R2, NR1CONR1R2, (NH2)n, -NH2CH2, NH2CH2CF3,-CH(CF3)-(CH)n-CO-N- R1R2,CH(CF3)-(CH)n-SO2, (CH)n;CH(OH)(CF3)(Heretocycle)R1, optionally substituted 3 to 8 membered carbocyclic ring, or 3 to 8 membered saturated, mono-, fused- or bridged heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, optionally substituted 3 to 8 membered heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S or SO2, wherein the substitution may independently be R1 and R2 at any position of the ring;C1- 6alk-aryl, ArC1-6alkyl;

R1 and R2 are independently selected from the group comprising H, halo, CN, CF3, hydroxyl, Amino, SO2, SO2, C1-C6 Alkyl, SO2-C3-C8-cycloalkyl, CH2CN, CH2CF3, unsubstituted or substituted C1-C6 straight or branched alkyl wherein the substituents are selected from halo, OH, CN, C1-C6 alkoxy, optionally substituted NH2, C1-C6 alkylsulfonyl, optionally substituted CONH2, unsubstituted or substituted C3-C8 carbocyclyl or 3-8 membered heterocyclic ring with 1-3 heteroatoms selected from O, N and S, SO2, C1-C6 straight or branched alkenyl, C1-C6 straight or branched alkynyl, , C1-C6 alkyloxy; C1-C6 alkylamino, C1-C6 alkylcarbonyl, C(O)-C3-C8-cycloalkyl, heteroalkyl, optionally substituted CONH2, C3–C8 cycloalkyl, C3–C8cycloalkenyl, C3– C8heterocycloalkyl, C3–C8heterocycloalkenyl, carbocycyl, aryl, and heteroaryl, - CH(CF3)-(CH)n-CO-N-R3R4, -CH(CF3)-(CH)n-SO2-NR3R4, CH(CF3)-(CH)n-NR3R4,

CH(CF3)-NR3R4, CH(CF3)-(CH)n-SO2-CHR3R4, wherein cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, carbocyclyl, aryl and heteroaryl groups are optionally substituted;

R3 and R4 are H, independently CH3, C3–C8 cycloalkyl;

R5 is unsubstituted or substituted 3-8 membered carbocylic ring or heterocyclic ring containing 1 to 3 heteroatoms selected from the group comprising O, N, S, SO2;

R6, is independently H, C1-C6 straight or branched alkyl, halogen;

X can be connected to Y at any atom so as to arrive at chemically viable bond;

n is 0 to 3.

4. The 1H-imidazo[4,5-b]pyridin-2(3H)-one compounds as claimed in claim 1, their pharmaceutically acceptable salts and isomers of formula III:

Wherein;

Y may be present at any position of the pyridine ring, preferably, at 4th or 5th position of pyridine;

Y is H, R1, R2, halo, CN, -CO-, COR1, (CH2)n, -(CH2)nCN -, CH2CF3, COOH, - COOR1, -CON(R1)2,-SO2(CH2)n,-SO2N(R1)2, -OCOR1, -NR1COR1, -CONH, CONR1R2, -CO(NH2)n(CH2)nSO2; -CONH(CH2)nOH, CONH(CH2)nSO2R1R2, - CONH-(CH2)nCF3, -CONH(CH2)nCF3,-NHCONH(CH2)nCF3, , -CH(CF3)-(CH)n-

CO-N-R1R2,CH(CF3)-(CH)n-SO2-(CH)n; CH(OH)(CF3)(Heretocycle)R1, NHCONHR1, -NHCOR1R2, NR1CONR1R2, (NH2)n, -NH2CH2-, NH2CH2CF3,

wherein the heterocycle is optionally substituted 3 to 8 membered saturated, mono-, fused- or bridged heterocyclic ring containing 1 to 3 heteroatoms, selected from the group comprising O, N, S;

wherein the substitution may independently be R1 and R2 at any position of the heterocyclic ring; C1-6alk-aryl, Ar C1-6 alkyl;

R1 and R2 are absent or independently selected from the group comprising H, halo, CN, CF3, hydroxyl, Amino, SO2, SO2C1-C6 Alkyl, CH2CF3, C1-C6 straight or branched alkyl, C1-C6 straight or branched alkenyl, C1-C6 straight or branched alkynyl, halo-C1- C6 alkyl, C1-C6 alkyloxy; C1-C6 alkylamino,

n is 0 to 3.

5. The compounds of formula III, as claimed in claim 4, selected from the group comprising:

1133. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-methylpiperidin-4-yl)ethanol;

1134. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(tetrahydro-2H-pyran-4-yl)ethanol;

1176. 7-(1-(4-(1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridine;

1181. 7-(1-(5-((S)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1182. 7-(1-(5-((R)-1,1,1-trifluoro-4-(methylsulfonyl)butan-2-yl)pyridin-2-yl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine;

1225. (R)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)- 2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol;

1226. (S)-1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)- 2,2,2-trifluoro-1-(1-isopropylpyrrolidin-3-yl)ethanol;

1231. 1-(6-(4-(3H-imidazo[4,5-b]pyridin-7-yl)-1H-pyrazol-1-yl)pyridin-3-yl)-2,2,2- trifluoro-1-(1-methylazetidin-3-yl)ethanol.

6. The process for preparing the compounds as claimed in claim 1, comprising the steps of:

Wherein,

X is C, N,

R2 and R3 is H,

R1:

Wherein

X is C, N,

R1 is CN and R2 is H R3;

Wherein,

X is C, N,

R1 CF3 and R2 is H,

R3;

Wherein,

X is C, N,

R1 is CF3 and R2 is OH

R3

X is C, N,

R1 is CF3 and R2 is OCH3 R3

7. The process for preparing the compounds as claimed in claim 1, comprising the steps of:

X1= O or H R2= H or–CH3 R3= H or–CH3

R1;

R4;

8. A process for preparing the compounds as claimed in claim 1, comprising the steps of:

X1, Y, Z is C, N.

R3 is H, O, carbocycle,

9. A process for preparing the compounds as claimed in claim 1, comprising the steps of:

X is C, N.

R2 is H, O, carbocycle,

R1 =

10. A Pharmaceutical composition comprising the compounds as claimed in claim 1 along with pharmaceutically acceptable excipients.

11. The Pharmaceutical composition as claimed in claim 10, when administered as orally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, intracistemally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms.

12. Compounds as claimed in claim 1, as selective JAK 1 inhibitor.

13. Compounds as claimed in claim 1 for their use in treating cancer, including, but not limited to, carcinomas, sarcomas, lymphomas, leukemias, myelomas, germ cell tumors, blastomas, tumors of the central and peripheral nervous system and other tumors including melanomas, seminoma and Kaposi's sarcoma and the like, acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, asthma, autoimmune hemolytic anemia, autoimmune thyroiditis, Crohn's disease, episodic lymphopenia with lymphocytotoxins, erythroblastosis fetalis, Goodpasture's syndrome, Graves' disease, Hashimoto's thyroiditis, hypereosinophilia, irritable bowel syndrome and other interbowel diseases, Lupus, myasthenia gravis, myocardial or pericardial inflammation, pancreatitis, polymyositis, psoriasis, Reiter's syndrome, scleroderma, systemic analphylaxis, ulcerative colitis, nephritis (including glomerulonephritis), gout, arthritis (such as rheumatoid arthritis and osteoarthritis), erythema, dermatitis, dermatomyositis, bronchitis, cholecystitis, sepis and gastritis.