WO2022058896A1

WO2022058896A1 - Inhibitors of low molecular weight protein tyrosine phosphatase for management of metabolic disorder

Info

Publication number: WO2022058896A1
Application number: PCT/IB2021/058391
Authority: WO
Inventors: Rajiv Sharma; Sanjay Kumar; Brijesh Kumar Srivastava; Sanjay GITE; Sandeep SHEDAGE; Pravin Kadam; Parind Dholakia
Original assignee: Cadila Healthcare Limited
Priority date: 2020-09-15
Filing date: 2021-09-15
Publication date: 2022-03-24

Abstract

The present invention relates to novel modulators of low molecular weight protein tyrosine phosphatases and their use for the treatment of diseases or conditions mediated by LMPTP. Further, the present invention relates to processes of preparing such compounds, their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, their safe pre-mixtures with polymers such as HPMC, HPMC-AS, Copovidone and methods for using such compounds, and pharmaceutical compositions containing them.

Description

INHIBITORS OF LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE FOR MANAGEMENT OF METABOLIC DISORDER

FIELD OF THE INVENTION

BACKGROUND OF THE INVENTION

Obesity is one of the greatest health threats of this century. Obesity is usually defined using the body mass index [BMI= weight (kg)/height (m)² ]. People with BMI of 30 and above (27 and above for Chinese and Asian people) possess great risk of co-morbid diseases such as hypertension, type 2 diabetes, and dyslipidemia. The worldwide explosion of obesity and related disorders are generally attributed to the western dietary habits (high sugar, high fat diet). Obesity is also one of the metabolic syndromes. Insulin resistance is an important component of metabolic syndrome. Protein tyrosine phosphatases regulate insulin signaling are therapeutic targets for insulin resistance syndrome including Low Molecular Weight Protein Tyrosine Phosphatases (LMPTP).

LMPTP is highly expressed in liver, adipocytes, muscles and heart. In vitro and In vivo evidences suggest that low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity.

The low molecular weight protein tyrosine phosphatase has been proposed to regulate insulin signaling through IR dephosphorylation. LMPTP, encoded by the ACPI gene, is a small (18 kDa), ubiquitous cytosolic class II PTP expressed as two isoforms, LMPTP-A and LMPTP-B, which arise from alternative splicing. Human genetic evidence suggests that LMPTP promotes type 2 diabetes and insulin resistance. ACPI alleles encoding low LMPTP enzymatic activity protect against hyperlipidemia in obese subjects and associate with lower glycemic levels in diabetic and non-diabetic subjects. Selective LMPTP chemical inhibitors would be highly valuable for assessing activity-dependent LMPTP functions and its potential as a drug target. Developing selective, cell-permeable PTP inhibitors have been complicated by features of the PTP active-site, which is small, highly charged, and well-conserved among different PTPs.

Inhibition studies with rationally designed inhibitors of the human low molecular weight protein tyrosine phosphatase, is reported in Bioorg. Med. Chem. 2004, 12, 1867-1880. Structure-based discovery of new small inhibitors of low molecular weight protein tyrosine phosphatase is reported in Eur. J. Med. Chem. 2007, 42, 1102-1108.

Cynthia et al. reported “Identification of novel inhibitors for a low molecular weight protein tyrosine phosphatase via virtual screening” in Bioorg. Med. Chem. 2010, 18, 5449- 5456.

Alastair J. Barr published a review: Protein tyrosine phosphatases as drug targets: Strategies and Challenges of inhibitor development in Future Med. Chem. 2010, 2, 1563- 1576.

Low molecular weight protein tyrosine phosphatases as emerging targets for the design of novel therapeutic agents is reported in J. Med. Chem. 2012, 55, 2-22 by Rosanna Maccari et al.

Synthesis biological activity and structure activity relationships of new benzoic acid based protein tyrosine phosphatase inhibitors endowed with insulinomimitic effects in mouse C₂CI₂ skeletal muscle cells is reported in Eur. J. Med. Chem. 2014, 71, 112-117.

Russell G. Kerr et al. have reported Natural Products with protein tyrosine phosphatase inhibitor activity in Methods, 2014, 65, 229-238. Inhibition of low molecular weight protein tyrosine phosphatase by an Induced -Fit Mechanism is published in J. Med. Chem. 2016, 59, 9094-9106 by Zhong- Yin Zhang et al.

La Jolla Institute of Allergy & Immunology and Sanford Burnham Medical Research Institute disclosed small molecules in Wipo patent application WO 2016061280 titled “Inhibitors of Low molecular weight protein tyrosine phosphatase and uses thereof’ and in an aspect provided compounds having the formula (IA) & (IB).

Stephanie M Stanford et al. have reported “Diabetes reversal by inhibition of the low molecular weight protein tyrosine phosphatase” and published the results in Nat. Chem. Biol. 2017, 13(6), 624-632.

Sanford Burnham Medical Discover Institute disclosed “Inhibitors of low molecular weight protein tyrosine phosphatase (LMPTP) and uses thereof “in Wipo patent application WO 2018204176 described the following formula (I) or a pharmaceutically acceptable salt or solvate thereof.

Sanford Burnham Prebys Medical Discover Institute has disclosed “Inhibitors of low molecular weight protein tyrosine phosphatase (LMPTP) and uses thereof. WIPO patent application WO 2019136093 described the following formula (I) or a pharmaceutically acceptable salt or solvate thereof.

Shirin R. DeSouza et al. have reported SAR of non-hydro lysable analogs of pyridoxal 5’- phosphate against low molecular weight protein tyrosine phosphatase isoforms in Bioorg. Med. Chem. Lett. 2020, 30, 127342

We herein disclose novel compounds of formula (I) useful as LMPTP modulator which may have beneficial effect in the treatment of diseases, which are mediated by LMPTP and methods for their preparation.

SUMMARY OF THE INVENTION

The present invention provides compounds which are modulators of LMPTP and their use for the treatment of diseases, which are mediated by LMPTP over expression. The novel compounds are defined by the general formula (I) as given below. The compounds of the present invention are useful in the treatment of the human or animal body, by inhibition of LMPTP expression. The compounds of this invention are therefore suitable for the treatmen t/mitigation or regulation of metabolic disorders. EMBODIMENTS OF THE INVENTION

The main objective of the present invention is to provide novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, pharmaceutically acceptable polymers, pharmaceutically acceptable excipients, and pharmaceutical compositions containing them or their mixtures suitable for the treatment of conditions, diseases, or disorders associated with LMPTP activity.

In an embodiment is provided a process for the preparation of novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, pharmaceutically acceptable solvates , pharmaceutically acceptable polymers, pharmaceutically acceptable excipients and pharmaceutical compositions containing them.

In another embodiment is provided pharmaceutical compositions containing compounds of general formula (I), their tautomeric forms, their pharmaceutically acceptable salts, solvates and their mixtures having pharmaceutically acceptable carriers, solvents, diluents, excipients and other media normally employed in their manufacture.

In a further another embodiment is provided the use of the novel compounds of the present invention for the treatment/mitigation or regulation of metabolic disorders or other diseases or conditions mediated by low molecular weight protein tyrosine phosphatases (LMPTP), by administering a therapeutically effective & non-toxic amount of the compound of formula (I), or their pharmaceutically acceptable compositions to the mammals.

DETAILED DESCRIPTION OF THE INVENTION

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

their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, pharmaceutically acceptable polymers and pharmaceutical compositions wherein

‘A’ represents the following rings:

‘X’ & ‘Y’ independently represents N or CR where R is selected from H, -CO, optionally substituted group selected from (C₁-C₆)alkyl;

‘Z’ independently represents a covalent bond, -O-, -NR₁, -NR₁C(O)-, -C(O)NR₁-, -OC(O)- or -C(O)-O-, where R₁ may optionally selected from cycloalkyl, heterocyclic, heteroaryl, fused heterocycle bicyclic ring, spiro or bridged system;

‘T’ independently represents a bond, optionally substituted group selected from (C₁-C₆)alkyl, (C₂-C₆)alkylene, (C₂-C₆)alkyne, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene; In an embodiment ‘T’ may be absent;

R & R at each occurrence independently represents hydrogen, -NR R , OR , SR , substituted or unsubstituted groups selected from (C₁-C₆)alkyl, heteroalkyl, (C₃- C₇)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro or bridged cyclic system; each of R³ & R⁴ at each occurrence independently represents hydrogen, halogen, haloalkyl optionally substituted group selected from (C₁-C₆)alkyl or (C₃-C₇)cycloalkyl;

R⁵, R⁶ & R⁷ at each occurrence independently represents hydrogen, haloalkyl optionally substituted group selected from (C₁-C₆)alkyl or (C₃- C₇)cycloalkyl;

When any of above defined group is substituted the substitutions on them may be selected from those described above or may additionally be selected from hydrogen, hydroxy, cyano, halo, haloalkyl, haloalkyloxy, alkylthio optionally substituted group selected from (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₃-C₇)cycloalkyl, (C₁-C₆)alkoxy, -COR₁₂, - CSR₁₂, C(O)OR₁₂, C(O)-R₁₂, -C(O)-NR₁₂R₁₃, -C(S)-NR₁₂R₁₃, -SO₂R₁₂ group, wherein each of R₁₂ and R₁₃ is independently selected from hydrogen, optionally substituted group selected from (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₃-C₇)cycloalkyl, aryl, heteroaryl, heterocyclyl groups;

In a preferred embodiment ‘A’ represents the following rings:

In another preferred embodiment, the groups referred to above may comprise of:

"Alkyl" by itself or as part of another substituent, means, unless otherwise stated, a straight- or branched-chain, fully saturated aliphatic hydrocarbon radical having the number of carbon atoms designated. For example, "C_1-6alkyl" refers to a hydrocarbon radical, either straight- or branched-chain, that contains from 1 to 6 carbon atoms and that is derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane. Alkyl includes branched-chain isomers of straight-chain alkyl groups, such as isopropyl, t-butyl, isobutyl, sec-butyl, and the like. Representative alkyl groups include straight- and branched-chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms. Further representative alkyl groups include straight and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. “Haloalkyl” group is selected from an alkyl radical, as defined above, suitably substituted with one or more halogens; such as perhaloalkyl, more preferably, perfluoro (C₁-C₆)alkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, mono or polyhalo substituted methyl, ethyl, propyl, butyl, pentyl or hexyl groups;

“Haloalkoxy” group is selected from suitable haloalkyl, as defined above, directly attached to an oxygen atom, more preferably groups selected from fluoromethoxy, chloromethoxy, fluoroethoxy, chloroethoxy and the like; the groups “heterocycloxy”, “heterocylylalkoxy” are selected from suitable heterocyclyl, heterocylylalkyl groups respectively, as defined above, attached to an oxygen atom; the “thioalkyl” group used either alone or in combination with other radicals, denotes an alkyl group, as defined above, attached to a group of formula -SR’, (sulfur and its oxidized forms) where R’ represents hydrogen, alkyl or aryl group, e.g. thiomethyl, methyl thiomethyl, phenylthiomethyl and the like, which may be optionally substituted. "Cycloalkyl" or “alicyclic” refers to a saturated or partially saturated cyclic group of from 3 to 14 carbon atoms and no ring heteroatoms and having a single ring or multiple rings including fused, bridged, and spiro ring systems. Examples of cycloalkyl or alicyclic groups include, for instance, adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, and cyclohexenyl.

"Halo" or "halogen" by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. Additionally, terms such as "haloalkyl", are meant to include an alkyl in which one or more hydrogen is replaced by halogen atoms that can be the same or different, in a number ranging from one up to the maximum number of halogens permitted e.g. for alkyl, (2m'+1), where m' is the total number of carbon atoms in the alkyl group. For example, the term "haloC_1- ₈alkyl" is meant to include difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4- chlorobutyl, 3 -bromopropyl, and the like. Additionally, term "haloalkoxy" refers to an alkoxy radical substituted with one or more halogen atoms. In one group of embodiments, the haloalkyl and haloalkoxy groups have from one to five or from one to three halogen atoms. Examples of haloalkoxy groups include difluoro methoxy and trifluoro methoxy.

As used herein, the term "heterocycle" or "heterocyclic system" is intended to mean a stable 4 to 7-membered monocyclic or 7 to 14-membered bicyclic heterocyclic ring which is saturated, partially saturated or unsaturated (aromatic), and which consists of carbon atoms & also contains from 1 to 3 hetero atoms independently selected from the group consisting of N, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The term heterocycle as used in the specification includes both aromatic and non-aromatic single or fused cyclic system containing at least one heteroatom selected from N, O and S. The nitrogen and sulfur hetero atoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. A skilled person is well aware of the terms "heterocycle" or "heterocyclic system" and the present invention encompasses all such variations, alterations of definitions which are within the scope of such a skilled person. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. In a further optional embodiment, nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these hetero atoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1. As used herein, the term "aromatic heterocyclic system" is intended to mean a stable 5 to 7 membered monocyclic or bicyclic or 7 to 14 membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, O and S. It is preferred that the total number of S and O atoms in the aromatic heterocycle is not more than 1. Also included are fused ring, bridged bicyclic heterocycles, Spirocompounds containing, for example, the above heterocycles. "Heteroaryl" means an aromatic or partially aromatic heterocycle that contains at least one ring heteroatom selected from O, S and N. Heteroaryls thus include heteroaryls fused to other kinds of rings, such as aryls, cycloalkyls, and heterocycles that are not aromatic. Examples of heteroaryl groups include; pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, oxazolyl, oxadiazolyl, thiadiazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, triazinyl, thienyl, pyrimidyl, benzisoxazolyl, benzoxazolyl, benzthiazolyl, benzothiadiazolyl, dihydrobenzofuranyl, indolinyl, pyridazinyl, indazolyl, isoindolyl, dihydrobenzothienyl, indolinyl, pyridazinyl, indazolyl, isoindolyl, dihydrobenzothienyl, indolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, napthyridinyl, carbazolyl, benzodioxolyl, quinoxalinyl, purinyl, furazanyl, isobenzylfuranyl, benzimidazolyl, benzofuranyt, benzothienyl, quinolyl, indolyl, isoquinolyl, dibenzofuranyl etc. For heterocyclyl and heteroaryl groups, rings and ring systems containing from 3-15 carbon atoms are included, forming 1-3 rings.

As used herein, the term “fused rings” is intended to mean, one ring is a 4-7-membered monocyclic ring which is saturated, partially saturated, or unsaturated (aromatic) and comprises a 4-membered heterocycle, 5-membered heterocycle, 6-membered heterocycle, 7-membered heterocycle, or a carbocycle, each fused to a second ring. The second ring is a 5 to 7 membered monocyclic ring which is saturated, partially unsaturated or unsaturated (aromatic), and comprises a 4-membered heterocycle, 5- membered heterocycle, 6-membered heterocycle, 7-membered heterocycle or a carbocycle.

As used herein, "carbocycle" or "carbocyclic residue" is intended to mean any stable monocyclic or bicyclic or tricyclic ring, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycle include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin); The term "substituted," as used herein, means that any one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. The term "substituted," as used herein, means that any one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound.

The term 'optional' or ‘optionally' means that the subsequent described event or circumstance may or may not occur, and the description includes instances where the event or circumstance occur and instances in which it does not. For example, ‘Optionally substituted alkyl' means either 'alkyl' or 'substituted alkyl'. Further an optionally substituted group includes an unsubstituted group.

The term "combination therapy" means the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single table t/capsule having a fixed ratio of active ingredients or in multiple, separate tablet/capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.

The phrase "therapeutically effective" is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder. This amount will achieve the goal of reducing or eliminating the said disease or disorder.

The term "therapeutically acceptable" refers to those compounds (or salts, prodrugs, tautomers, zwitterionic forms, etc.) which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and are effective for their intended use. As used herein, reference to "treatment" of a patient is intended to include prophylaxis. The term "patient" means all mammals including humans. Examples of patients include humans, cows, dogs, cats, goats, sheep, pigs, and rabbits. Preferably, the patient is a human.

Compounds of formula (I) may contain one or more asymmetric centers and can thus occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. The present invention is meant to comprehend all such isomeric forms of the compounds of formula (I), either as single species or mixtures thereof.

Some of the compounds described herein contain olefin double bonds, and unless specified otherwise, are meant to include both E and Z geometric isomers.

Some of the compounds described herein may exist with different points of attachment of hydrogen, referred to as tautomers. Such an example may be a ketone and its enol form known as keto-enol tautomers. The individual tautomers as well as mixture thereof are encompassed with compounds of formula (I).

List of Abbreviation

DMF: Dimethyl formamide

DCM: Dichloromethane

EDAC.HC1: N-(3-Dimethyl aminopropyl)-N’ -ethyl carbodiimide hydrochloride,

HOBT: 1 -Hydroxy benzotriazole

TFA: Trifluoro acetic acid

DCC: Dicyclohexylcarbodiimide

DIPEA: Disopropyl ethyl amine

EtOAc: Ethyl acetate h: Hour(s) rt : room temperature min: Minute(s) t_Ret: Retention time

HCl: Hydrochloric acid

RT: Room temperature [25-30 °C]

CS₂CO₃: Cesium carbonate

TEA: Triethyl amine

HBTU : N,N,N',N'-Tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate

Instrument details

Mass spectrum was recorded on LC-MS 2010-A Shimadzu.

HPLC purity was determined by using Agilent 1100 instrument.

HPLC Column: YMC J Sphere C18 (150X4.6 mm)4μ

Mobile phase: 0.05 % TFA in water: ACN gradient.

Flow rate: 1.0 mL/min.

Wave length: UV at 220 nm.

UPLC was determined on Acquity Ultra performance instrument.

UPEC Column: BEHC18 (2.1x 100mm) 1.7 μ

Mobile phase: 0.05 % TFA in water: ACN gradient.

Flow rate: 0.04 mL/min

NMR spectrum: Bruker Avanc 400 MHz

Suitable groups and substituents on the groups may be selected from those described anywhere in the specification. Particularly useful compounds may be selected from:

1-(3-((5-(4-(diethylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-4-(114- pyrrolidin-2-ylium-1-yl)- 114-piperidin-2-ylium chloride hydrochloride; 5-(4-((diethylamino)methyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine;

N,N-diethyl-4-(7-((3-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide;

4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-N,N- diethylbenzamide dihydrochloride ;

N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine trihydrochloride;

N-(3-(piperidin-1-yl)propyl)-5-(4-(pyrrolidin-1-ylmethyl)phenyl)thieno[3,2-b]pyridin-7- amine;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(4-(ethylsulfonyl)piperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)-5-(4- ((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-amine;

(4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(piperidin-1-yl)methanone;

8-(3-((5-(4-(piperidine-1-carbonyl )phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1-oxa- 8-azaspiro[4.5]decan-2-one; piperidin-1-yl(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)methanone;

8-(3-((5-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1- oxa-8-azaspiro[4.5]decan-2-one; (4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone; morpholino(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)methanone;

4-(7-((3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-N,N- diethylbenzamide;

4-(7-((3-(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)-N,N-diethylbenzamide;

4-(7-((3-(4-(cyclopropylsulfonyl) piperazin- 1-yl) propyl) amino)thieno[3,2-b]pyridin-5- yl)-N,N-diethylbenzamide; pyrrolidin-1-yl(4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone; 1-(2-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)- 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)ethan-1-one;

5-(4-methoxyphenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

(4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3 ,2-b]pyridin-5-yl)phenyl)( 1 - oxidothiomorpholino)methanone ;

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-ethylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-thiomorpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine; thiomorpholino(4-(7-((3-(4-thiomorpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone; (1-oxidothiomorpholino)(4-(7-((3-thiomorpholinopropyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)methanone; N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)-5-(4-(trifluoromethyl)phenyl) thieno[3,2- b]pyridin-7-amine;

N-(3-thiomorpholinopropyl)-5-(4-(trifluoromethyl)phenyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(piperidin-1-yl)propyl)-5-(4-(trifluoromethyl)phenyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-morpholinopiperidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl) thieno [3 , 2-b] pyridin-7-amine ;

N-(3-(pyrrolidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno[3,2-b]pyridin-7- amine;

N-(3-(piperidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno[3,2-b]pyridin-7- amine;

N-(3-morpholinopropyl)-5-(4-(l -(pyrrolidin-1-yl)ethyl)phenyl)thieno[3,2-b]pyridin-7- amine;

5-(4-( 1 -(pyrrolidin-1-yl)ethyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin- 7-amine;

N-(3-(piperidin-1-yl)propyl)-5-(4-(l -(pyrrolidin-1-yl)ethyl)phenyl)thieno[3,2-b]pyridin-7- amine; morpholino(4-(7-((4-(4-(pyrrolidin-1-yl)piperidin-1-yl)butan-2-yl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone;

5-(4-(1-(piperidin-1-yl)ethyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine;

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-methylpiperazin-1-yl)propyl) thieno [3 , 2-b] pyridin-7-amine ; (4-(7-((3-(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)phenyl)(thiomorpholino)methanone; tri-hydrochloride salt of N-(3-(piperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl) phenyl)thieno[3,2-b]pyridin-7-amine;

(4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)phenyl) (thiomorpholino)methanone ;

N-(3-(4-morpholinopiperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl)phenyl) thieno[3,2- b]pyridin-7-amine;

(4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(thiomorpholino)methanone;

(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)phenyl) (thiomorpholino)methanone ;

5-(4-((2-isopropyl-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)methyl)phenyl)-N-(3- (pyrrolidin-1-yl)propyl)thieno[3 ,2-b]pyridin-7 -amine ;

5-(4-((2-isopropyl-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)methyl)phenyl)-N-(3- (piperidin-1-yl)propyl)thieno[3 ,2-b]pyridin-7 -amine ;

5-(4-((diethylamino)methyl)phenyl)-2-methyl-N-(3-(4-morpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

N, N-dimethyl-4-(7-((3-(2-oxo-1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino) thieno [3,2-b]pyridin-5-yl)benzamide;

4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-N,N- dimethylbenzamide ;

8-(3-((5-(4-((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1-oxa-

8-azaspiro[4.5]decan-2-one; N-(3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-((diethylamino)methyl)phenyl) thieno [3 , 2-b] pyridin-7-amine ;

N-(3-(piperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl)phenyl)thieno[3,2-b]pyridin-7- amine;

N-(3-(2-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-((diethylamino)methyl)phenyl) thieno [3 , 2-b] pyridin-7-amine ;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine;

N-(3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)-5-(4-((diethylamino)methyl) phenyl)thieno[3,2-b]pyridin-7-amine;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(4-morpholinopiperidin-1-yl)propyl) thieno[3,2- b]pyridin-7-amine;

5-(4-((diethylamino)methyl)phenyl)-N-(3-morpholinopropyl)thieno[3,2-b]pyridin-7- amine;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl) thieno [3 , 2-b] pyridin-7-amine ;

N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)-5-(4-(pyrrolidin-1-ylmethyl)phenyl) thieno [3 , 2-b] pyridin-7-amine ;

N-(3-(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)-5-(4- ((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-amine; trihydrochloride salt of N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide; dihydrochloride salt of N,N-diethyl-4-(7-((3-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide; N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide;

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide;

N,N-diethyl-4-(7-((3-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)benzamide;

4-(7-((3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)- N,N-diethylbenzamide dihydrochloride;

5-(4-methoxyphenyl)-N-(3-(piperidin-1-yl) propyl) thieno [3,2-b]pyridin-7-amine;

N,N-diethyl-2-fluoro-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

N,N-diethyl-2-fluoro-4-(7-((3 -(pyrrolidin-1-yl)propyl)amino)thieno [3 ,2-b]pyridin-5 - yl)benzamide;

3-chloro-N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide;

5-(4-((diethylamino)methyl)-3-fhrorophenyl)-N-(3-(4-morpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

5-(4-((diethylamino)methyl)-3-fhrorophenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine;

(2-fluoro-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone;

4-(7-((3-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)- N,N-diethyl-2-fluorobenzamide;

N,N-diethyl-3-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide;

(2-fluoro-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone; 3-(7-((3-(7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-N,N- diethylbenzamide;

3-(7-((3-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)- N,N-diethylbenzamide;

5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno [3,2- b]pyridin-7-amine;

5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(4-phenylpiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

2-chloro-N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

2-chloro-N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno [3,2-b]pyridin-5-yl)benzamide;

4-(7-((3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)-2-chloro-N,N-diethylbenzamide;

5-(3-((diethylamino)methyl)phenyl)-N-(3-(hexahydrocyclopenta[c]pyrrol-2(1H)- yl)propyl)thieno[3,2-b]pyridin-7-amine;

(2-chloro-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone;

(2-chloro-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone;

(3-chloro-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(thiomorpholino)methanone;

(3-chloro-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(thiomorpholino)methanone; 2-chloro-N,N-diethyl-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(4-ethylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-aminopiperidin-1-yl)propyl)-5-(4-methoxyphenyl)thieno[3,2-b]pyridin-7-amine trihydrochloride ;

5-(4-methoxyphenyl)-N-(3-(4-(methylsulfonyl)piperidin-1-yl)propyl)thieno[3,2-b]pyridin-

7-amine;

(4-methylpiperazin-1-yl)(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)methanone;

5-(4-((diethylamino)methyl)-3-fhrorophenyl)-N-(3-(4-methylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(4-methylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

(3-chloro-4-(7-((3-(4-methylpiperazin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone;

8-(3-((5-(4-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1-oxa-8- azaspiro [4.5] decan-2-one ;

5-(4-methoxyphenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)-5-(4-methoxyphenyl)thieno[3,2- b]pyridin-7-amine;

N-(3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)-5-(4-(morpholinomethyl)phenyl) thieno [3 , 2-b] pyridin-7-amine ;

(4-(7-((3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone; N-(3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-(morpholinomethyl)phenyl)thieno [3,2-b]pyridin-7-amine;

N-(3-(piperidin-1-yl)propyl)-5-(thiophen-3-yl)thieno[3,2-b]pyridin-7-amine;

5-phenyl-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-methylpiperazin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno[3,2-b] pyridin-7-amine;

5-(4-(morpholinomethyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine trihydrochloride;

5-(4-(morpholinomethyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine;

N-cyclopropyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin- 5-yl)benzamide;

N-cyclopropyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

4-(7-((3-(4-(cyclopropylsulfonyl) piperazin- 1-yl) propyl) amino)thieno[3,2-b]pyridin-5- yl)-N,N-diethylbenzamide

The compounds of the present invention may be prepared using the methods described below, together with conventional techniques known to those skilled in the art of organic synthesis or variation thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to those described below, where all symbols are as defined earlier.

General Scheme 1: Synthesis of compounds of general formula (I)

Amino ester derivative of formula [II] was cyclized with suitable reagent selected from diethyl malonate, urea and like; solvents selected from MeOH, EtOH results in cyclized Dihydroxy compound of formula [III]. Dihydroxy compound of formula [III] was chlorinated by thionyl chloride or phosphorous oxychloride to afford dichloro derivative [IV]. The derivative of formula IV was subjected to Suzuki coupling conditions or nucleophilic substitution reaction to get derivative of formula V. The derivative of formula V was appropriately substituted to get derivative of formula VI having a leaving group “L” {such as OMs, halo, tosylate etc.}. Displacement reaction with formula VI and desired R2 using suitable bases such as potassium carbonate, sodium carbonate and like in solvent selected from DCM, DMF and like, afforded compound of formula [I].

The compound of formula [II] and [IV] can be synthesized as per the general procedures known in the art along with suitable variations as are well known to a skilled person, in the art such as following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis; Wiley & Sons: New York, Volumes 1-21; R. C. LaRock, Comprehensive Organic Transformations, 2.nd edition Wiley- VCH, New York 1999; Comprehensive Organic Synthesis, B. Trost and I. Fleming (Eds.) vol. 1-9 Pergamon, Oxford, 1991; Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees (Eds) Pergamon, Oxford 1984, vol. 1-9; Comprehensive Heterocyclic Chemistry II, A. R. Katritzky and C. W. Rees (Eds) Pergamon, Oxford 1996, vol. 1-1 1 ; and Organic Reactions, Wiley & Sons: New York, 1991, Volumes 1 40, to name some of the known literature processes.

The pharmaceutically acceptable salts forming a part of this invention may be prepared by treating the compound of formula (I) with suitable acids in suitable solvents by processes known in the art.

The invention is further exemplified by the following examples below, which provides some of the several preferred embodiments of the present invention. These examples are provided merely as representative embodiments and should not be construed to limit the scope of the invention in any way. Example 1: Preparation of 1-(3-((5-(4-(diethyl carbamoyl) phenyl)thieno[3,2-b]pyridin-7- yl)amino)propyl)-4-(114-pyrrolidin-2-ylium-1-yl)-114-piperidin-2-ylium chloride hydrochloride

Preparation of ethyl 5,7-dihydroxythieno[3,2-b]pyridine-6-carboxylate (IX)

150 mL of ethanol was taken in a 500 mL three-necked flask, and added SODIUM ETHOXIDE (32.5 g, 477 mmol) followed by addition of methyl 3-aminothiophene-2- carboxylate (25 g, 159 mmol) and DIETHYL MALONATE (60.7 mL, 398 mmol). The mixture was heated under reflux over a period of 10 h. The reaction mixture was cooled to room temperature and filtered to give ethyl 5,7-dihydroxythieno[3,2-b]pyridine-6- carboxylate (15 g, 62.7 mmol, 39.4 % yield) as white solid. ¹H NMR (DMSO-d₆, δ): 12.02 (brs, 1H), 8.09-8.10 (t, 1H), 6.98 (d, J = 5.2 Hz, 1H), 4.29-4.35 (q, 2H), 1.26 1.34 (m, 3H).

Preparation of thieno [3,2-b]pyridine-5,7-diol (X)

Ethyl 5,7-dihydroxythieno[3,2-b]pyridine-6-carboxylate of formula IX (80 g, 334 mmol) is placed in a 2 L round bottom flask. HYDROCHLORIC ACID (250 mL, 8229 mmol) diluted with Water (250 mL) was added to the formula IX. Mixture was stirred under reflux. The reaction mixture was cooled to room temperature and potassium carbonate was added under stirring and adjusted to pH=5 to afford gray solid, which was filtered, and dried to obtain thieno[3,2-b]pyridine-5,7-diol of formula X (50 g, 299 mmol, 89 % yield). ¹H NMR (DMSO-d₆, δ): 10.02 (brs, 1H), 7.33-7.37 (m, 1H), 6.73-6.77 (m, 1H), 4.64-4.66 (m, 1H),

Preparation of 5,7-dichlorothieno[3,2-b]pyridine (XI)

Placed thieno [3,2-b]pyridine-5,7-diol (60 g, 359 mmol) in a 1 L RB flask , followed by addition of POCI₃ (100 mL, 1077 mmol). The reaction mixture is heated to reflux over a period of 12 h. The reaction mixture was cooled to RT. Reaction mixture was basified, using saturated sodium bicarbonate solution. The resulting precipitate was filtered, and washed by excess of DM water to get off white solid 5,7-dichlorothieno[3,2-b]pyridine of formula XI (40 g, 196 mmol, 65.5 % yield). ¹H NMR (DMSO-d₆, δ): 7.87 (d, J = 5.6 Hz, 1H), 7.55 - 7.66 (m, 1H), 7.37 (s, 1H);

Preparation of 4-(7-chlorothieno [3,2-b]pyridin-5-yl)-N,N-diethylbenzamide(XII)

Placed (4-(diethylcarbamoyl)phenyl)boronic acid (16.25 g, 73.5 mmol), 5,7- dichlorothieno[3,2-b]pyridine (15 g, 73.5 mmol), Potassium Carbonate (20.32 g, 147 mmol) in a 150 mL three-neck flask followed by addition of solution of 1,4-Dioxane (100 mL) in Water (20 mL) , Nitrogen was purged in the reaction mixture over a period of 20 min and added Tetrakis (1.699 g, 1.470 mmol). The reaction mixture was heated at 80 ° C over a period of 6.5 h. The solvents were removed under reduced pressure on a rotatory evaporator. The residue obtained was diluted with DCM (750 mL), washed with DM water. The organic layer was separated, dried over anhydrous sodium sulfate. The solvents were removed on a rotatory evaporator to afford off brown solid. The crude product was purified using column chromatography. The required fractions were pooled , solvents were removed under reduced pressure to afford solid, which was triturated with ethyl acetate to get off white solid of 4-(7-chlorothieno[3,2-b]pyridin-5-yl)-N,N-diethylbenzamide XII (9 g, 26.1 mmol, 35.5 % yield). ¹H NMR (DMSO-d₆, δ): 8.23-8.32 (m, 4H), 7.72 (d, J = 5.6 Hz, 1H), 7.48-7.50 (m, 2H), 3.46 (brs, 2H), 3.24 (brs, 2H), 1.09-1.19 (m, 6H).

Preparation of N,N-diethyl-4-(7-((3-hydroxypropyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide(XIII)

Placed 4-(7-chlorothieno[3,2-b]pyridin-5-yl)-N,N-diethylbenzamide XII (4.5 g, 13.05 mmol) and 3- 3 -aminopropan-1-ol (9.80 g, 130 mmol) in a 100 mL three-neck RB flask. The reaction mixture was heated at 120 ° C over a period of 6.5 h. The solvents were removed on a rotatory evaporator under reduced pressure to get crude solid. The crude residue was diluted with DCM (750 mL) and washed with DM water. The organic layer was separated, dried over anhydrous Na₂SO₄ and solvents were removed on a rotatory evaporator to get off brown solid. The crude product obtained, was purified using column chromatography to get off white solid of N,N-diethyl-4-(7-((3- hydroxypropyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide XIII (4 g, 10.43 mmol, 80 % yield). ¹H NMR (DMSO-d₆, δ): 8.15 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 5.2 Hz, 1H), 7.43- 7.45 (m, 3H), 7.01 (s, 1H), 6.79-6.88 (brt, 1H), 4.60-4.63 (brt, 1H), 3.40-4.63 (m, 6H), 3.24 (brs, 2H), 1.79-1.86 (m, 2H), 1.10-1.19 (m, 6H).

Preparation of 3-((5-(4-(diethyl carbamoyl) phenyl) thieno [3,2-b]pyridin-7- yl)amino)propyl methanesulfonate (XIV)

Placed N,N-diethyl-4-(7-((3-hydroxypropyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide XIII (11 g, 28.7 mmol), TEA (4.00 mL, 28.7 mmol) and DCM (100 mL) in 500 mL three-necked flask, and reaction mixture cooled up to -3 to 0 °c followed by drop wise addition of solution of methane sulfonyl chloride (2.68 mL, 34.4 mmol) in DCM (100 mL) over a period of 45 min. The progress of reaction was monitored by TLC using mobile phase 75% EtOAc in n-Hexane. The reaction mixture was diluted with DCM and extracted with saturated bicarbonate solution. The organic layer was dried on anhydrous sodium sulphate, filtered and solvents were removed on a rotatory evaporator under reduced pressure to get 3-((5-(4-(diethylcarbamoyl) phenyl) thieno [3,2-b]pyridin-7- yl)amino)propyl methanesulfonate XIV(13 g, 28.2 mmol, 98 % yield). ¹H NMR (DMSO-d₆, δ): 8.18 (d, J = 8.4 Hz, 2H), 7.95-7.97 (m, 1H), 7.60-7.63 (m, 3H), 7.03 (s, 1H), 6.93 (brs, 1H), 4.35-4.38 (m, 2H), 3.20-3.55 (m, 6H), 3.16 (s, 1H), 2.10-2.12 (m, 2H), 1.15- 1.21 (m, 6H). Preparation of N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide (XV)

Placed 3-((5-(4-(diethylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl methanesulfonate XIV (0.40 g, 0.867 mmol) in round bottomed flask followed by addition of DMF (5 mL) at 25 °C. To this, sequentially, added 4-(pyrrolidin-1-yl) piperidine (0.201 g, 1.300 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.320 mL, 1.733 mmol). The reaction mixture was stirred and heated to 90-95 °C over a period of 8 h. The solvents were removed on a rotatory evaporator under reduced pressure to obtain off brown solid. The crude product was purified by preparative HPLC to get off white solid of N,N-diethyl- 4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide XV (0.15 g, 0.287 mmol, 33.1 % yield). ¹H NMR (DMSO-d₆, δ): 8.14 (d, J = 8 Hz, 2H), 7.94 (d, J = 5.2 Hz, 1H), 7.42 - 7.44 (m, 3H), 6.97 (brs, 2H), 3.24-3.44 (m, 6H), 2.84-2.87 (brd, 2H), 2.32-2.66 (m, 5H), 1.79-1.98 (m, 8H), 1.65 (m, 4H), 1.41 - 1.49 (m, 2H), 1.10-1.22 (m, 6H).

Example 1

Preparation of N, V-diethvl-4-(7-((3-(4-(pyrrolidin-1-yl) piperidin-1- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide trihydrochloride

Placed N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide XV (3.38 g, 6.50 mmol) and DCM (50 mL) in round bottom at 25 °C. To the solution was added methanolic-HCl (15-20%) solution (15 mL) dropwise and after complete addition the mixture was stirred at 28-25 °C over a period of 1 h. The solvents were removed on a rotatory evaporator to get off brown solid. The solid obtained was triturated with ethyl acetate to get off white solid of N,N-diethyl-4-(7-((3-(4- (pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide trihydrochloride . ¹H NMR (DMSO-d₆, δ): 14.66 (s, 1H), 11.20 (s, 1H), 11.83 (s, 1H), 9.24 (s, 1H), 8.39 - 8.38 (d, J = 5.6 Hz, 1H), 8.16 8.14 (d, J = 7.6 Hz, 2H), 7.77 - 7.73 (m, 1H), 7.63 - 7.60 (d, J = 8.4 Hz, 2H), 7.21(s, 1H), 3.50 (s, 5H ), 3.20 (m, 4H), 3.0 (m, 4H), 2.33 (m, 2H), 2.28 (m, 4H), 1.99 (m, 2H), 1.19 - 1.03 (m, 6H). The following examples were synthesized in the analogous manner and characterized.

Example 2

5-(4-((diethylamino) methyl) phenyl)-N-(3-(piperidin-1-yl) propyl) thieno [3,2- b]pyridin-7-amine

¹H NMR (DMSO-d6, δ): 8.01(d, J = 8.4 Hz, 2H), 7.93 (d, J = 5.6Hz, 1H), 7.44 - 7.40 (dd,

J = 8 Hz & 5.6 Hz, 1H), 7.38 (s, 2H), 7.01 - 6.99 (m, 1H), 6.92 (s, 1H), 3.57 (s, 2H ), 3.45 - 3.41 (m, 2H), 2.49 - 2.45 (m, 4H), 2.41- 2.35 (m, 5H), 1.84 - 1.76 (m, 2H), 1.58 - 1.53 (m, 4H), 1.41 - 1.40 (m, 2H), 0.99 - 0.98 (m, 6H).

Example 3 N,N-diethyl-4-(7-((3-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide

¹H NMR (DMSO-d6, δ ): 8.16 (d, J = 8.4 Hz, 2H), 7.93(d, J = 5.6 Hz, 1H), 7.64 (s, 1H), 7.45 - 7.43 (dd, J = 7.6 Hz & 3.2 Hz, 3H), 6.97 (s, 1H), 6.85 - 6.82 (m, 1H), 4.99 - 4.95 (m, 1H ), 4.19 - 4.16 (m, 1H), 3.51 - 3.45 (m, 4H), 3.12 (m, 1H), 3.10 (d, 1H), 2.95(d, 1H), 2.14 - 2.10 (m, 1H), 2.09 - 2.02 (m, 1H), 1.86 - 1.82 (m, 2H), 1.13 - 1.11 (m, 6H).

Example 4

4-(7-((3-(1-oxa-8-azaspiro [4.5] decan-8-yl) propyl) amino) thieno [3,2-b]pyridin-5- yl)-N,N-diethylbenzamide dihydrochloride

¹H NMR (DMSO-d6, δ): 14.2 (brs, 1H), 10.5 (brs, 1H), 9.05 (brs, 1H), 8.39 (d, J = 5.6 Hz, 1H), 8.09 (d, J = 8 Hz, 2H), 7.66-7.62 (m, 3H),7.20 (s, 1H), 3.76 -3.71 (m, 4H), 3.20-3.17 (m, 4H), 3.05-2.97 (m, 2H), 2.14-2.09 (m, 2H), 2.02-1.86 (m, 4H), 1.80-1.68 (m, 4H), 1.24-1.07 (m, 6H).

Example 5

N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-

5-yl)benzamide

¹H NMR (DMSO-d6, δ): 8.15 (d, J = 8.4 Hz, 2H), 7.96 (d, J = 5.6 Hz, 1H), 7.45-7.43 (m,

3H), 7.08-6.98 (m, 2H), 3.57-3.51 (m, 4H), 3.47-3.40 (m, 4H), 3.29-3.24 (m, 2H ), 2.96- 2.93 (m, 2H), 3.29-3.24 (m, 2H), 2.96-2.93 (m, 2H), 2.45-2.41 (m, 6H), 2.1 l(m, 1H), 1.89- 1.81 (m, 4H), 1.79-1.72 (m, 2H), 1.49 - 1.43 (m, 2H), 1.2 (s, 1H), 1.1 (s, 6H). Example 6

5-(4-((diethylamino)methyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-

7-amine trihydrochloride

¹H NMR (DMSO-d6, δ ): 14.78 (brs, 1H), 11.27 (s, 1H), 10.78 ( s, 1H), 9.21(s, 1H), 8.38 (d, J = 5.6 Hz, 1H), 8.22 (d, J = 7.6 Hz, 2H), 7.99 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 4.4Hz, 1H), 7.22 (s, 1H), 4.43 (s, 2H ), 3.24 - 3.73 (brs, 2H ), 3.16 - 3.01 (m, 6H), 2.88 - 2.81 (m, 2H), 2.19 - 2.16 (m, 2H), 1.91 - 1.68 (m, 4H), 1.42 (t, 6H).

Example 7 N-(3-(piperidin-1-yl) propyl)-5-(4-(pyrrolidin-1-ylmethyl) phenyl) thieno [3, 2-b] pyridin-7-amine

¹H NMR (DMSO-d6, δ): 8.02 (d, J = 8.2 Hz, 2H), 7.94(d, J = 8.8 Hz, 1H), 7.43 (d, J = 5.2 Hz, 1H), 7.42 - 7.38 (d, J = 7.6 Hz, 2H), 6.99 (m, 1H), 7.38 (t, 1H), 6.92 (s, 1H), 3.62 (s, 2H ), 3.46 - 3.41 (m, 2H), 2.45 -2.09 (m, 9H), 1.83 (m, 2H), 1.79 (m, 4H), 1.55 (m, 4H), 1.42 (m, 2H).

Example 8

5-(4-((diethylamino) methyl) phenyl)-N-(3-(4-(ethylsulfonyl) piperazin-1-yl) propyl) thieno [3,2-b]pyridin-7-amine

¹H NMR (DMSO-d6, δ): 8.01 (d, J = 8.4Hz, 2H), 7.92 (d, J= 5.6 Hz, 1H), 7.43 - 7.39 (m, 3H), 6.93 (s, 1H), 6.83 - 6.81 (m, 1H), 3.58 (s, 2H ), 3.45 - 3.40 (m, 2H), 3.18 (m, 4H), 3.09 - 3.01(m, 2H), 2.47 (m, 10H), 1.84 (m, 2H), 1.23 - 1.20 (m, 5H), 1.02 - 0.98 (m, 6H).

Example 9

N-(3-(4-(cyclopropylsulfonyl) piperazin-1-yl) propyl)-5-(4-((diethylamino) methyl) phenyl) thieno [3,2-b]pyridin-7-amine ¹H NMR (DMSO-d6, δ ): 8.09 (brs, 2H), 7.93 (m, 1H), 7.48 (brs, 2H), 7.43 (m, 1H), 6.98 (m, 1H), 6.79 (brs, 1H), 4.61 (t, 1H), 4.02 (m, 2H), 3.45 (m, 3H), 3.22 (brs, 2H), 2.57 (m,

10H), 1.84 (m, 2H), 1.23 - 0.92 (m, 10H).

Example 10

(4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5- y l)phenyl)(piperidin-1-yl)methanone

¹H NMR (DMSO-d6, δ): 8.16 (d, , J = 8.4 Hz, 1H), 7.95 (d, J = 5.6 Hz, 1H), 7.47-7.44 (m, 3H), 7.05 (t, J = 5.2 Hz, 1H), 6.98 (s, 1H), 3.69 (t, J = 6.8 Hz, 2H), 3.47-3.38 (m, 6H), 2.45-2.33 (m, 6H), 1.87-1.80 (m, 4H), 1.65-1.51 (m, 12H).

Example 11 8-(3-((5-(4-(piperidine-1-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1- oxa-8-azaspiro[4.5]decan-2-one

O ¹H NMR (DMSO-d6, δ): 8.15 (d, J = 8.0 Hz, 2H), 7.95 (d, J = 5.2 Hz, 1H), 7.46 (m, 3H), 6.99-6.96 (m, 2H), 3.61 (m, 2H), 3.48-3.44 (m, 3H), 2.68-2.60 (m, 3H), 2.47-2.33 (m, 8H), 1.99-1.55 (m, 14H).

Example 12 piperidin-1-yl(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)methanone

O ¹H NMR (DMSO-d6, δ): 9.3 (brs, 1H), 8.31 (bs,1H), 8.08 (d, J = 8.0 Hz, 2H), 7.61-7.54 (m, 3H), 7.13 (s, 1H), 3.74-7.62 (m, 4H), 3.53-3.38 (m, 4H), 3.23-2.84 (m, 6H), 1.99-1.80 (m, 2H), 1.71-1.42 (m, 8H) Example 13

8-(3-((5-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)- l-oxa-8-azaspiro[4.5]decan-2-one

¹H NMR (DMSO-d6, δ): 9.51 (brs, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.0 Hz,

2H), 7.67 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 5.6 Hz, 1H), 7.14 (s, 1H), 3.65-3.4 (m, 12H), 3.26-3.03 (m, 4H), 2.67-2.60 (m, 2H), 2.19-1.88 (m, 8H)

Example 14

(4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone

¹H NMR (DMSO-d6, δ): 9.43 (brs, 1H), 8.33 (s,1H), 8.07 (d, J = 8 Hz, 2H), 7.68 (d, J = 8 Hz, 2H), 7.56 (d, J = 5.6 Hz, 1H), 7.14 (s, 1H), 3.83-3.42 (m, 12H), 3.22-3.02 (m, 6H), 2.06-1.99 (m, 2H), 1.99-1.68 (m, 6H).

Example 15 morpholino (4-(7-((3-(piperidin-1-yl) propyl) amino) thieno [3,2-b]pyridin-5- yl)phenyl)methanone

1H NMR (DMSO-d6, δ): 9.43 (brs, 1H), 8.33 (s,1H), 8.07 (d, J = 8 Hz, 2H), 7.68 (d, J =

8 Hz, 2H), 7.56 (d, J = 5.6 Hz, 1H), 7.14 (s, 1H), 3.83-3.42 (m, 12H), 3.22-3.02 (m, 6H), 2.06-1.99 (m, 2H), 1.99-1.68 (m, 6H). Example 16

4-(7-((3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-

N,N -diethylbenzamide

¹H NMR (DMSO-d6, δ ): 8.14 (d, J = 8.4 Hz, 2H), 7.94 (d, J = 5.2Hz, 1H), 7.45 (d, J = 2.4 Hz, 2H), 7.43 (s, 1H), 6.99 - 6.98 (brs, 2H), 4.61 (s, 4H), 3.44 - 3.34 (m, 4H ), 3.29 -

3.26 (brs, 5H), 2.46 - 2.43 (m, 2H), 1.65 - 1.61 (t, 2H), 1.16 - 1.10 (m, 6H).

Example 17

4-(7-((3-(4-(4-(cyclopropylsulfonyl) piperazin-1-yl) piperidin-1-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)-N,N-diethylbenzamide

¹H NMR (DMSO-d6, δ ): 8.15 (d, J = 8.4Hz, 2H), 7.96 (d, J = 4.2 Hz, 1H), 7.45 - 7.43 (dd, J = 5.6 Hz & 1.6 Hz, 3H), 7.00 - 6.98 (brs, 2H), 3.46 - 3.43 (brs, 4H ), 3.33 (brs, 2H), 3.28 (brs, 4H), 2.98 (brs, 2H), 2.60 - 2.56 (brs, 5H), 2.46 (brs, 2H), 2.33 (brs, 1H), 1.83 - 1.80 (brs, 4H), 1.73 - 1.70 (m, 2H), 1.50 - 1.48 (m, 2H), 1.14 (s, 2H), 1.1 (m, 6H), 0.99

(d, 2H), 0.97 (d, 2H).

Example 18

4-(7-((3-(4-(cyclopropylsulfonyl) piperazin-1-yl) propyl) amino)thieno[3,2-b]pyridin-

5-yl)-N,N-diethylbenzamide

¹H-NMR (δ ppm) (In DMSO) : δ 8.02 (d, J = 8.4Hz, 2H), 7.92 (d, J = 5.2Hz, 1H), 7.43 - 7.37 (m, 3H), 6.93 (s, 1H), 6.88 (s, 1H), 3.55 (s, 2H), 3.44 - 3.43 (m, 2H), 2.67 - 2.62 (m, 9H), 2.17 (m, 3H), 1.81 (m, 2H); LC-MS: 481.7 (M)⁺, Purity by UPLC: 94.59%.

Example 19 pyrrolidin-1-yl(4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone

¹H NMR (DMSO-d6, δ ): 8.14 (d, J = 8.4 Hz, 2H), 7.95(d, J = 5.2 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 5.6 Hz, 1H), 6.99 (m, 2H), 3.51 - 3.44 (m, 6H ), 2.88 (d, 2H), 2.33(m, 6H), 1.94 - 1.81 (m, 12H), 1.66 (brs, 4H), 1.47 (m, 2H), 1.23 (brs, 2H); 0.85 (m, 1H).

Example 20

N-cyclopropyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide ¹H-NMR (δ ppm) (In DMSO) : δ 8.51 (d, J = 4.4Hz, 1H), 8.17 (d, J = 8.4Hz, 2H), 7.91 - 7.96 (m, 3H), 7.46 (d, J = 5.6Hz, 1H), 7.04-7.06 (brt, 1H), 7.0 (s, 1H), 3.32-3.48 (m, 2H), 2.86-2.89 (m, 1H), 2.33 - 2.39 (m, 4H), 1.82-1.85 (brt, 2H), 1.56-1.59 (m, 4H), 1.42 (brs, 2H), 0.70-0.74 (m, 4H);

Example 21 5-(4-methoxyphenyl)-N-(3-(piperidin-1-yl) propyl) thieno [3,2-b]pyridin-7-amine ¹H NMR (DMSO-d6, δ ): 8.04 (d, J = 8 Hz, 2H), 7.90 (d, J = 5.2 Hz, 1H), 7.41-7.47 (brt, 1H), 7.02 (d, J = 8 Hz, 2H), 6.96 (brs, 1H), 6.87 (s, 1H), 3.82 (s, 3H ), 3.59 - 3.74 (m, 4H), 1.84 (brs, 2H), 1.58 (brs, 4H), 1.42 (brs, 2H).

Example 22 (4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(1-oxidothiomorpholino)methanone

¹H NMR (DMSO-d6, δ ): 8.04 (d, J = 8 Hz, 2H), 7.90 (d, J = 5.2 Hz, 1H), 7.41-7.47 (brt, 1H), 7.02 (d, J = 8 Hz, 2H), 6.96 (brs, 1H), 6.87 (s, 1H), 3.82 (s, 3H ), 3.59 - 3.74 (m, 4H), 1.84 (brs, 2H), 1.58 (brs, 4H), 1.42 (brs, 2H). LC-MS: 581.6 (M)⁺, Purity by

UPLC:95.06%

Example 23

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-ethylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (DMSO-d6, δ ): 7.94 (d, J = 5.6Hz, 1H), 7.90 (dd, J = 8Hz & 1.6Hz, 1H), 7.84 (dd, J = 12Hz & 1.6 Hz, 1H), 7.53 (t, 1H), 7.44 (d, J = 5.6Hz, 1H), 6.97 - 6.96 (brs, 2H), 3.62 (s, 2H), 3.47 - 3.39 (m, 3H), 2.47 - 2.40 (m, 10H), 2.34 - 2.28 (m, 4H), 1.82 - 1.79 (m, 2H), 1.03 - 0.97 (m, 9H); LC-MS: 483.8 (M)⁺, Purity by UPLC:96.84%

Example 24

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-thiomorpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (DMSO-d6, δ ): 7.95 (d, J = 5.2Hz, 1H), 7.91 - 7.83 (m, 2H), 7.51 (t, 1H), 7.44 (d, J = 5.6Hz, 1H), 7.00 - 6.96 (m, 2H), 3.61 (s, 2H), 3.47 - 3.34 (m, 2H), 2.96 - 2.94 (m, 2H), 2.75 (m, 4H), 2.57 (m, 5H), 2.47 (m, 3H), 2.41 - 2.33 (m, 2H), 2.24 (m, 1H), 1.85 - 1.77 (m, 4H), 1.62 - 1.51 (m, 4H), 1.00 (m, 6H); LC-MS: 555.7 (M)⁺, Purity by

UPLC:97.07%.

Example 25 thiomorpholino(4-(7-((3-(4-thiomorpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone

¹H-NMR (δ ppm) (In DMSO) : δ 8.16 (d, J = 8.4Hz, 2H), 7.96 (d, J = 5.6Hz, 1H), 7.49 (d, J = 8.4Hz, 2H), 7.45 (d, J = 5.6Hz, 1H), 7.01 (d, 2H), 3.9 - 3.4 (m, 6H), 2.97 (dd, 2H), 2.77 - 2.57 (m, 12H), 2.40 (t, 2H), 2.2 (m, 1H), 1.83 - 1.78 (m, 4H), 1.7 - 1.4 (m, 4H);

LC-MS: 581.6 (M)⁺, Purity by UPLC:94.89%.

Example 26 (1-oxidothiomorpholino)(4-(7-((3-thiomorpholinopropyl)amino)thieno[3,2-b]pyridin- 5-yl)phenyl)methanone

¹H-NMR (δ ppm) (In DMSO) : δ 8.18 (d, J = 8.4Hz, 2H), 7.96 (d, J = 5.2Hz, 1H), 7.55 (d, J = 8.4Hz, 2H), 7.45 (d, J = 5.6Hz, 1H), 6.99 (s, 1H), 6.95 (s, 1H), 4.4 (m, 1H), 3.85 - 3.63 (m, 2H), 3.49 - 3.38 (m, 2H), 3.034 - 2.97 (m, 2H), 2.86 - 2.83 (m, 2H), 2.67 (m, 9H), 2.46 - 2.45 (m, 2H), 1.83 (m, 2H).; LC-MS: 514.5 (M)⁺, Purity by UPLC:92.38%.

Example 27

N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)-5-(4-(trifluoromethyl)phenyl) thieno[3,2-b]pyridin-7-amine

¹H-NMR (δ ppm) (In DMSO) : δ 8.18 (d, J = 8.4Hz, 2H), 7.95 (d, J = 5.6Hz, 1H), 7.55 (d, J = 8.4Hz, 2H), 7.45 (t, 1H), 7.02 (m, 1H), 6.99 (s, 1H), 4.4 - (brs, 1H), 3.9 - 3.5 (m, 3H), 3.45 - 3.42 (m, 2H), 3.03 - 2.84 (m, 6H), 2.40 (m, 5H), 2.33 (m, 1H), 1.86 - 1.79 (m, 4H), 1.68 - 1.65 (m, 2H), 1.6 - 1.4 (m, 1H), 1.39 - 1.3 (m, 2H).; LC-MS: 580.1 (M)⁺, Purity by UPLC: 91.58%. Example 28 N-(3-thiomorpholinopropyl)-5-(4-(trifluoromethyl)phenyl)thieno[3,2-b]pyridin-7- amine

¹H NMR (δ ppm) (In DMSO) : δ 8.32 (d, J = 8Hz, 2H), 7.98 (d, J = 5.2Hz, 1H), 7.84 (d, J

= 8Hz, 2H), 7.48 (d, J = 5.6Hz, 1H), 7.03 (s, 1H), 6.99 (m, 1H), 3.47 - 3.43 (m, 2H), 2.65 (brs, 8H), 2.45 (m, 2H), 1.85 - 1.80 (m, 2H).; LC-MS: 438.1 (M)⁺, Purity by UPLC: 97.27%.

Example 29 N-(3-(piperidin-1-yl)propyl)-5-(4-(trifluoromethyl)phenyl)thieno[3,2-b]pyridin-7- amine

¹H-NMR (δ ppm) (In DMSO) : δ 8.33 (d, J = 8Hz, 2H), 7.98 (d, J = 5.2Hz, 1H), 7.84 (d, J = 8.4Hz, 2H), 7.48 (d, J = 5.6Hz, 1H), 7.13 (m, 1H), 7.03 (s, 1H), 3.48 - 3.33 (m, 2H), 2.42 - 2.33 (m, 6H), 1.85 - 1.79 (m, 2H), 1.58 - 1.53 (m, 4H), 1.4 (m, 2H).; LC-MS:

420.1 (M)⁺, Purity by UPLC: 97.98%.

Example 30

N-(3-(4-morpholinopiperidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl) thieno[3,2-b]pyridin-7-amine

¹H-NMR (δ ppm) (In DMSO) : δ 8.33 (d, J = 8 Hz, 2H), 7.97 (d, J = 5.2 Hz, 1H), 7.84 (d, J = 8 Hz, 2H), 7.47 (d, J = 5.2Hz, 1H), 7.04 - 7.0 (m, 2H), 3.61 (m, 4H), 3.46 (m, 2H), 2.45 - 2.38 (m, 6H), 1.86 - 1.81 (m, 2H).; ); LC-MS: 422.1 (M)⁺, Purity by UPLC: 97.43%.

Example 31

¹H-NMR (δ ppm) (In DMSO) : δ 8.02 (d, J = 8Hz, 2H), 7.93 (d, J = 5.6Hz, 1H), 7.43 (d, J = 5.2Hz, 1H), 7.38 (d, J = 8Hz, 2H), 6.93 (d, 2H), 3.58 - 3.55 (m, 5H), 3.44 - 3.42 (m, 2H), 2.96 - 2.93 (m, 2H), 2.66 - 2.62 (m, 8H), 2.46 - 2.40 (m, 8H), 2.1 (m, 1H), 1.85 - 1.72 (m, 5H), 1.47 - 1.44 (m, 2H), 1.23 (s, 1H) ); LC-MS:550.9 (M-l)⁺, Purity by UPLC: 97.88%.

Example 32 N-(3-(pyrrolidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno[3,2- b]pyridin-7-amine

¹H-NMR (δ ppm) (In DMSO) : δ 8.03 (d, J = 8Hz, 2H), 7.91 (d, J = 5.6Hz, 1H), 7.43 (d, J = 5.6Hz, 1H), 7.39 (d, J = 8Hz, 2H), 7.07 (t, 1H), 6.95 (s, 1H), 3.55 (s, 2H), 3.48 - 3.43 (m, 2H), 2.64 - 2.61 (m, 9H), 2.57 (m, 2H), 2.49 (m, 4H), 1.85 (t, 2H), 1.73 (brs, 4H) ); LC-MS: 452.1 (M)⁺, Purity by UPLC: 96.27%.

Example 33

N-(3-(piperidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno[3,2- b]pyridin-7-amine

¹H-NMR (δ ppm) (In DMSO) : δ 8.03 (d, J = 8Hz, 2H), 7.92 (d, J = 5.2Hz, 1H), 7.43 (d, J = 5.6Hz, 1H), 7.39 (d, J = 8Hz, 2H), 7.01 (t, 1H), 6.92 (s, 1H), 3.55 (s, 2H), 3.44 (m, 2H), 2.64 - 2.63 (m, 8H), 2.42 - 2.35 (m, 6H), 1.84 - 1.78 (m, 2H), 1.57 - 1.55 (m, 4H), 1.41 (s, 2H) ); LC-MS: 466.9 (M)⁺, Purity by UPLC: 97.25%.

Example 34 N-(3-morpholinopropyl)-5-(4-(1-(pyrrolidin-1-yl)ethyl)phenyl)thieno[3,2-b]pyridin-7- amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.0 (d, J = 8 Hz, 2H), 7.92 (d, J = 5.2 Hz, 1H), 7.43 - 7.39 (m, 3H), 6.12 (s, 1H), 6.88 (m, 1H), 3.61 (brs, 4H ), 3.45 (m, 2H), 3.24 (m, 1H), 2.44 - 2.33 (m, 8H), 1.84 - 1.80 (m, 2H), 1.68 (brs, 4H), 1.33 (brs, 3H) ); LC-MS: 451.2 (M)⁺, Purity by UPLC: 96.05%.

Example 35

5-(4-(1-(pyrrolidin-1-yl)ethyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2- b ]pyridin-7 -amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.0 (d, J = 8 Hz, 2H), 7.90 (d, J = 5.6 Hz, 1H), 7.43 - 7.38 (m, 3H), 7.06 (t, 1H), 6.94 (s, 1H), 3.47 - 3.43 (m, 2H ), 3.26 - 3.22 (m, 1H), 2.67

(m, 4H), 2.46 (m, 4H), 2.33 (brs, 2H), 1.84 (m, 2H), 1.73 (s, 4H), 1.68 (s, 4H), 1.34 - 1.32 (d, 3H); LC-MS: 435.4 (M)⁺, Purity by UPLC: 97.57%.

Example 36 N-(3-(piperidin-1-yl)propyl)-5-(4-(1-(pyrrolidin-1-yl)ethyl)phenyl)thieno[3,2- b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.0 (d, J = 8 Hz, 2H), 7.92 (d, J = 5.2 Hz, 1H), 7.43 -

7.38 (m, 3H), 6.99 (brs, 1H), 6.91 (m, 1H), 3.43 (brs, 2H ), 3.26 - 3.21 (m, 1H), 2.41 - 2.33 (m, 8H), 1.81 (m, 2H), 1.68 (s, 4H), 1.55 (s, 4H), 1.40 (s, 2H), 1.33 (brs, 3H), 2.50 (brs, 2H); LC-MS: 449.3 (M)⁺, Purity by UPLC: 98.14%.

Example 37 morpholino(4-(7-((4-(4-(pyrrolidin-1-yl)piperidin-1-yl)butan-2-yl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone

¹H NMR(δ ppm) (DMSO-d6, δ): 8.15 (d, J = 8 Hz, 2H), 7.95 (d, J = 4.8 Hz, 1H), 7.58 - 7.40 (m, 3H), 7.06 (s, 1H), 6.73 (d, 1H), 4.0 (brs, 1H ), 3.4 (m, 5H), 3.3 (m, 6H), 2.82 (m, 2H), 2.40 (m, 3H), 1.91 (brs, 3H), 1.78 (brs, 4H), 1.66 (brs, 4H), 1.46 - 1.43 (m, 2H), 1.26 (brs, 3H) ); LC-MS: 548.3 (M)⁺, Purity by UPLC: 97.45%.

Example 38

5-(4-(1-(piperidin-1-yl)ethyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.1 - 7.90 (dd, 3H), 7.43 - 7.36 (dd, 3H), 7.05 (s, 1H),

6.94 (s, 1H), 3.46 (brs, 3H), 3.32 (brs, 3H ), 2.33 (brs, 5H), 1.90 (brs, 1H), 1.83 (brs, 2H), 1.73 (brs, 4H), 1.48 (brs, 4H), 1.32 - 1.31 (m, 6H) ); LC-MS: 449.2 (M)⁺, Purity by UPLC: 96.96%.

Example 39

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-methylpiperazin-1-yl)propyl) thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 7.95 - 7.83 (dd, 3H), 7.51 (t, 1H), 7.44 (d, J = 5.2 Hz, 1H), 6.97 (s, 1H), 6.93 (s, 1H), 3.62 (s, 2H), 3.47 - 3.44 (m, 2H ), 2.47 - 2.33 (s, 4H), 2.16 (s, 3H), 1.84 - 1.77 (m, 2H), 1.04 -0.99 (m, 6H) ); LC-MS: 470 (M)⁺, Purity by UPLC: 95.04%.

Example 40

(4-(7-((3-(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)phenyl)(thiomorpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.16(d, J = 8.4 Hz, 2H), 7.97 (d, J = 5.2 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 5.2 Hz, 1H), 6.99 (brs, 2H), 3.88 (brs, 2H), 3.62 (brs, 2H ), 3.46 - 3.44 (m, 2H), 3.17 (brs, 4H), 2.96 (brs, 2H), 2.67 - 2.50 (m, 8H), 2.33 (m, 2H), 2.22 (m, 1H), 1.89 - 1.79 (m, 4H), 1.73 - 1.70 (m, 2H), 1.52 - 1.47 (m, 2H), 1.0 - 0.95 (m, 2H), 0.93 - 0.91 (m, 2H) ); LC-MS: 669.2 (M)⁺, Purity by UPLC: 98.32%.

Example 41

Tri-hydrochloride salt of N-(3-(piperidin-1-yl)propyl)-5-(4-(piperidin-1- ylmethyl)phenyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 14.80 (brs, 1H), 11.28 (brs, 1H), 10.79 (brs, 1H), 9.20

(s, 1H), 8.38 (d, J = 5.2 Hz, 1H), 8.21 (d, J = 7.6 Hz, 2H), 7.94 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 5.2 Hz, 1H), 7.21 (s, 1H), 4.39 - 4.38 (s, 2H), 3.73 (brs, 2H), 3.40 - 3.13 (m, 5H ), 3.06 - 2.80 (m, 4H), 2.18 (m, 2H), 1.87 - 1.73 (m, 11H), 1.42 - 1.36 (m, 2H) ); LC-MS:

448.1 (M-HC1)⁺, Purity by UPLC: 95.56%.

Example 42

(4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)phenyl)

(thiomorpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ): 8.16 (d, J = 8 Hz, 2H), 7.94 (d, J = 5.2 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 5.2 Hz, 1H), 7.13 (m, 1H), 7.01 (s, 1H), 3.88 (brs, 2H), 3.61 (brs, 2H ), 3.49 - 3.45 (m, 2H), 2.67 - 2.58 (m, 7H), 2.50 (m, 11H), 11.84 (m, 2H), 1.74 (m, 4H) ); LC-MS: 467.4 (M)⁺, Purity by UPLC: 96.67%.

Example 43

N-(3-(4-morpholinopiperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl)phenyl) thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.09 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 5.6 Hz, 1H), 7.43 - 7.41 (d, J = 5.6 Hz, 1H), 7.37 (d, J = 8.42 Hz, 2H), 6.94 - 6.92 (m, 2H), 3.57 (s, 5H), 2.94 (brs, 2H), 1.88 - 1.67 (m, 11H), 1.84 (m, 2H), 1.74 (m, 21H), 1.51 - 1.50. (m, 5H), 1.44 - 1.24 (m, 2H); LC-MS: 534.6 (M)⁺, Purity by UPLC: 93.18%.

Example 44

(4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(thiomorpholino)methanone

¹H NMR (δ ppm) DMSO-d6, δ): 8.16 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 5.2 Hz, 1H), 7.5 (d,

J = 8.4 Hz, 2H), 7.45 (d, J = 5.2 Hz, 1H), 7.01 - 6.98 (m, 2H), 3.88 (brs, 2H), 3.57 - 3.42 (brs, 6H), 3.38 (m, 2H), 2.94 (m, 2H), 2.67 (brs, 4H), 2.45 - 2.41 (m, 6H), 2.14 (m, 1H), 1.99 - 1.73 (m, 6H), 1.49 - 1.41 (m, 2H); LC-MS: 566.7 (M)⁺, Purity by UPLC: 91.95%. Example 45

(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)phenyl)

(thiomorpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.16 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 5.2 Hz, 1H), 7.49 (d, J = 8 Hz, 2H), 7.45 (d, J = 5.6 Hz, 1H), 7.07 (t, 1H), 6.98 (s, 1H), 3.88 (brs, 2H), 3.61 (brs, 2H), 3.47 - 3.43 (m, 2H), 2.67 (m, 5H), 2.41 - 2.33 (m, 5H), 1.85 - 1.82 (m, 2H), 1.57 - 1.55 (m, 4H), 1.4 (brs, 2H) ); LC-MS: 481.4 (M)⁺, Purity by UPLC: 98.42%.

Example 46 5-(4-((2-isopropyl-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)methyl)phenyl)-N-(3-

(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.06 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 5.2 Hz, 1H), 7.47 - 7.42 (m, 4H), 7.07 (t, 1H), 6.97 (s, 1H), 4.44 - 4.34 (m, 1H), 3.97 (s, 2H), 3.68 (s, 4H), 3.48 - 3.44 (m, 2H), 2.67 (m, 2H), 2.33 - 2.47 (m, 4H), 1.87 - 1.80 (m, 2H), 1.74 (s, 4H),

1.39 - 1.37 (d, 6H) ); LC-MS: 501.4 (M)⁺, Purity by UPLC: 95.22%.

Example 47

5-(4-((2-isopropyl-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)methyl)phenyl)-N-(3-

(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.06 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 5.2 Hz, 1H), 7.47 - 7.42 (m, 4H), 7.07 (t, 1H), 6.97 (s, 1H), 4.44 - 4.34 (m, 1H), 3.97 (s, 2H), 3.68 (s, 4H), 3.48 - 3.44 (m, 2H), 2.67 (m, 2H), 2.33 - 2.47 (m, 4H), 1.87 (m, 2H), 1.80 (m, 3H), 1.39 (d, 6H), 1.35 (d, 3H) ); LC-MS: 515.4 (M)⁺, Purity by UPLC: 96.91%.

Example 48

5-(4-((diethylamino)methyl)phenyl)-2-methyl-N-(3-(4-morpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 7.98 (d, J = 8 Hz, 2H), 7.38 (d, J = 8 Hz, 2H), 7.13 (d, J = 6.8 Hz, 1H), 6.87 - 6.85 (d, 2H), 3.57 (brs, 6H), 3.39 (m, 2H), 3.16 (brs, 1H), 2.96 (d, 2H), 2.57 (brs, 2H), 2.47 (m, 3H), 2.45 - 2.40 (m, 2H), 2.16 (m, 1H), 1.91 - 1.72 (m, 6H), 1.53 - 1.72 (m, 6H), 1.53 (d, 2H), 0.99 - 0.95 (m, 10H) ); LC-MS: 536.4 (M)⁺, Purity by UPLC: 966.3%.

Example 49

N, N-dimethyl-4-(7-((3-(2-oxo-1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)benzamide

¹H NMR (δ ppm) (DMS0-d6, δ ): 8.15 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 5.6 Hz, 1H), 7.50 (d, J = 8 Hz, 2H), 7.46 - 7.44 (m, 1H), 7.01 - 6.96 (m, 2H), 3.4 (m, 2H), 3.0 (d, 6H), 2.60 - 2.41 (m, 4H), 2.05 (m, 2H), 1.98 (s, 4H), 1.85 - 1.78 (m, 6H) ); LC-MS: 493.3 (M)⁺, Purity by UPLC: 88.9%.

Example 50

4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-

N,N -dimethylbenzamide

¹H NMR (δ ppm) (DMS0-d6, δ ): 8.14 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 5.6 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 5.6 Hz, 1H), 7.05 (m, 1H), 6.99 (s, 1H), 3.69 (t, 2H), 3.43 (m, 2H), 3.01 - 2.47 (d, 6H), 2.42 - 2.33 (m, 4H), 1.91 (s, 3H), 1.88 - 1.80 (m, 4H), 1.65 - 1.59 (m, 5H) ); LC-MS: 479.3 (M)⁺, Purity by UPLC: 94.85%.

Example 51 8-(3-((5-(4-((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1- oxa-8-azaspiro[4.5]decan-2-one

¹H NMR (δ ppm) (DMSO-d6, δ): 8.03 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 5.6 Hz, 1H), 7.44 - 7.41 (m, 3H), 6.95 - 6.90 (m, 2H), 3.6 (s, 2H), 3.4 (m, 2H), 2.6 - 2.4 (m, 12H), 1.99 - 1.91 (m, 2H), 1.84 - 1.71 (m, 6H), 1.0 (m, 8H) ); LC-MS: 507.4 (M)⁺, Purity by UPLC: 91.05%.

Example 52

N-(3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-((diethylamino)methyl)phenyl) thieno[3,2-b]pyridin-7-amine

¹H NMR(δ ppm) (DMSO-d6, δ ): 8.01 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 5.2 Hz, 1H), 7.43 -

7.39 (m, 3H), 7.0 (brs, 1H), 6.92 (s, 1H), 3.69 (t, 2H), 3.58 (s, 2H), 3.44 - 3.43 (m, 2H), 2.51 - 2.42 (m, 1H), 1.86 - 1.81 (m, 4H), 1.66 - 1.58 (m, 6H), 1.004 (t, 6H) ); LC-MS: 493.4 (M)⁺, Purity by UPLC: 92.99%.

Example 53 N-(3-(piperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl)phenyl)thieno[3,2-b]pyridin- 7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.02 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 5.6 Hz, 1H), 7.43 (d, J = 5.20 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.01 (t, 1H), 6.92 (s, 1H), 3.47 (s, 2H), 3.43 (m, 2H), 2.42 - 2.35 (m, 10H), 1.83 (m, 2H), 1.57 - 1.49 (m, 8H), 1.41 (brs, 4H) ); LC- MS: 449.5 (M)⁺, Purity by UPLC: 95.81%.

Example 54

N-(3-(2-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-((diethylamino)methyl)phenyl) thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMS0-d6, δ): 8.01 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 5.6 Hz, 1H), 7.44 - 7.39 (m, 3H), 6.97 (m, 1H), 6.93 (s, 1H), 3.72 (m, 2H), 3.59 (brs, 2H), 3.47 - 3.38 (m, 6H), 2.44 - 2.33 (m, 7H), 1.82 (m, 2H), 1.67 (m, 2H), 1.56 (m, 4H), 1.24 (1H), 1.01 (m, 6H) ); LC-MS: 493.3 (M)⁺, Purity by UPLC: 96.96%.

Example 55

5-(4-((diethylamino)methyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.01 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 5.6 Hz, 1H), 7.43 - 7.39 (m, 3H), 7.06 (m, 1H), 6.95 (s, 1H), 3.57 (m, 2H), 3.45 (m, 2H), 2.55 (m, 2H), 2.47 (m, 7H), 1.90 (s, 1H), 1.86 - 1.80 (m, 2H), 1.73 (brs, 4H), 1.01- 0.98 (m, 6H) ); LC-MS: 423.15 (M)⁺, Purity by UPLC: 96.64%. Example 56

N-(3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)-5-(4-((diethylamino)methyl) phenyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.01 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 5.6 Hz, 1H), 7.43 -

7.39 (m, 3H), 7.01 (s, 1H), 6.95 - 6.92 (m, 1H), 3.58 - 3.52 (m, 7H), 3.43 (m, 3H), 3.38 (m, 2H), 2.57 - 2.33 (m, 5H), 1.82 (m, 2H), 1.6 (m, 4H), 1.4 (m, 4H), 1.0 (m, 8H) ); LC- MS: 507.4 (M)⁺, Purity by UPLC: 91.0%.

Example 57 5-(4-((diethylamino)methyl)phenyl)-N-(3-(4-morpholinopiperidin-1-yl)propyl) thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.03 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 5.2 Hz, 1H), 7.43 - 7.39 (m, 3H), 6.94 - 6.92 (m, 2H), 3.57 (brs, 6H), 3.41 (m, 3H), 2.94 (m, 3H), 4.66 (m, 5H), 2.3 (m, 1H), 1.9 - 1.7 (m, 6H), 1.5 (m, 2H), 1.2 (m, 2H), 1.02 - 0.96 (m, 8H) ); LC-

MS: 522.3 (M)⁺, Purity by UPLC: 96.58%.

Example 58

5-(4-((diethylamino)methyl)phenyl)-N-(3-morpholinopropyl)thieno[3,2-b]pyridin-7- amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.01 (d, J = 8 Hz, 2H), 7.92 (d, J = 5.6 Hz, 1H), 7.43 - 7.39 (m, 3H), 6.93 (s, 1H), 6.88 (brs, 1H), 3.61 (m, 4H), 3.58 (s, 2H), 3.47 - 3.42 (m, 2H), 2.46 - 2.33 (m, 8H), 1.82 (m, 2H), 1.002 (m, 6H) ); LC-MS: 439.3 (M)⁺, Purity by UPLC: 99.64%.

Example 59

5-(4-((diethylamino)methyl)phenyl)-N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl) thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.01 (d, J = 8.4 Hz, 2H), 7.9 (d, J = 5.6 Hz, 1H), 7.44 -

7.36 (m, 3H), 6.9 (m, 2H), 3.7 (s, 3H), 3.5 - 3.3 (m, 4H), 2.9 (m, 3H), 2.39 (m, 6H), 1.94 (m, 4H), 1.8 (m, 4H), 1.76 (m, 4H), 1.4 (m, 2H), 1.0 (m, 6H) ); LC-MS: 506.4 (M)⁺, Purity by UPLC: 98.70%.

Example 60 N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)-5-(4-(pyrrolidin-1-ylmethyl)phenyl) thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.02 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 5.6 Hz, 1H), 7.43 (d, J = 5.6 Hz, 1H), 7.39 (d, J = 8.0 Hz, 2H), 6.93 (t, 2H), 3.62 (s, 2H), 3.42 (m, 3H), 2.87 (brs, 2H), 2.40 (m, 9H), 1.94 (m, 3H), 1.80 (m, 4H), 1.71 - 1.67 (d, 8H), 1.48 - 1.45 (m, 2H) ); LC-MS: 504.4 (M)⁺, Purity by UPLC: 95.08%.

Example 61

N-(3-(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)-5-(4-

((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 8.01 (d, J = 8.0 Hz, 2H), 7.94 (d, J = 5.6 Hz, 1H), 7.43 -

7.39 (m, 3H), 6.92 (m, 2H), 3.57 (s, 2H), 3.43 (d, 2H), 3.17 (m, 4H), 3.0 (m, 2H), 2.67 - 2.33 (m, 12H), 1.80 (m, 4H), 1.7 (m, 2H), 1.5 (m, 2H), 1.02 - 0.98 (m, 8H), 0.9 (m, 2H) ); LC-MS: 625.4 (M)⁺, Purity by UPLC: 99.33%.

Example 62 trihydrochloride salt of N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide

¹H NMR (δ ppm) (DMSO-d6, δ ): 14.67 (brs, 1H), 11.58 (brs, 1H), 11.02 (brs, 1H), 9.20 (brs, 1H), 8.38 (d, J = 5.2 Hz, 1H), 8.15 (d, J = 7.2 Hz, 2H), 7.74 (s, 1H), 7.62 (d, J = 8 Hz, 2H), 7.23 (brs, 1H), 3.99 (t, 2H), 3.87 (t, 2H), 3.74 (d, 2H), 3.66 (d, 2H), 3.34 (m, 2H), 3.23 - 3.17 (m, 6H), 3.11 - 3.08 (m, 2H), 2.94 - 2.93 (m, 2H), 2.23 (m, 3H), 2.19 (m, 4H),

1.19 -1.09 (d, 6H); LC-MS: 536.4 (M-HC1)⁺, Purity by UPLC: 95.28%.

Example 63

Dihydrochloride salt of N,N-diethyl-4-(7-((3-((3aR,6aS)-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide.

¹H NMR (δ ppm) (DMSO-d6, δ): 14.62 (brs, 1H), 10.97 (brs, 1H), 9.24 (brs, 1H), 8.39 (d, J = 5.6 Hz, 1H), 8.13 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 5.2 Hz, 1H), 7.64 (d, J = 8 Hz, 2H), 7.19 (s, 1H), 5.27 (t, 1H), 4.56 (t, 1H), 4.62 (m, 1H), 3.60 - 3.22 (m, 9H), 2.12 (brs, 2H), 1.23 - 1.17 (m, 8H); LC-MS: 494.3 (M-HC1)⁺, Purity by UPLC: 96.78%. Example 64

N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide

¹H NMR (δ ppm) (DMSO-d6, δ): 8.14 (d, J = 8 Hz, 2H), 7.94 (d, J = 5.2 Hz, 1H), 7.44 - 7.42 (m, 3H), 6.97 (brs, 2H), 3.44 - 3.43 (m, 4H), 3.24 (brs, 2H), 2.87 - 2.84 (m, 2H),

2.45 - 2.32 (m, 4H), 1.98 - 1.88 (m, 3H), 1.82 - 1.79 (m, 4H), 1.65 (s, 4H), 1.49 - 1.41 (m, 2H), 1.22 - 1.10 (m, 6H); LC-MS: 520.5 (M)⁺, Purity by UPLC: 99.28%.

Example 65

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide

¹H NMR (δ ppm) (DMSO-d6, δ): 8.15 (d, J = 8.0 Hz, 2H), 7.95 (d, J = 5.2 Hz, 1H), 7.46 - 7.43 (m, 3H), 7.1 (brs, 1H), 6.99 (brs, 1H), 3.45 (brs, 4H), 3.2 (m, 2H), 2.41 - 2.33 (m, 4H), 1.84 (brs, 2H), 1.57 (brs, 4H), 1.42 (brs, 2H), 1.19 - 1.16 (m, 6H); LC-MS: 451.5 (M)⁺, Purity by UPLC: 92.60%.

Example 66 N,N-diethyl-4-(7-((3-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)benzamide

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.16 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 5.2 Hz, 1H), 7.64 (s, 1H), 7.45 - 7.43 (m, 3H), 6.97 (s, 1H), 6.84 (m, 1H), 4.98 - 4.95 (m, 1H), 4.19 - 4.17 (m, 1H), 3.45 (brs, 4H), 3.33 - 3.26 (m, 2H), 3.10 (d, 1H), 2.90 (d, 1H), 2.14 - 2.11 (m, 1H), 2.10 - 2.09 (m, 1H), 1.9 - 1.8 (m, 2H), 1.23 - 1.18 (m, 8H); LC-MS: 494.4 (M)⁺,

Purity by UPLC: 93.18%.

Example 67

4-(7-((3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-

N,N -diethylbenzamide dihydrochloride

¹H NMR (δ ppm) (DMSO-d6, δ): 14.46 (brs, 1H), 10.54 (brs, 1H), 9.15 (brs, 1H), 8.39 (d, J = 5.2 Hz, 1H), 8.13 (d, J = 8 Hz, 2H), 7.69 (d, J = 5.2 Hz, 1H), 7.62 (d, J = 8 Hz, 2H), 7.21 (s, 1H), 3.7 (m, 2H), 3.5 (m, 5H), 3.29 - 2.96 (m, 8H), 2.1 (m, 2H), 1.8 (m, 2H), 1.7 (m, 2H), 1.5 (m, 2H), 1.3 (brs, 2H), 1.01 (d, 7H) ; LC-MS: 521.5 (M-HC1)⁺, Purity by UPLC: 99.33%.

Example 68

5-(4-methoxyphenyl)-N-(3-(piperidin-1-yl) propyl) thieno [3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.4-8.5 (brd, 1H), 7.9-8.1 (m, 2H), 7.5-7.8 (m, 3H), 7.12-7.16 (brd, 1H), 2.8-3.9 (m, 25H), 2.1-2.2 (m, 2H), 1.0-1.3 (m, 6H); LC-MS: 521.5 (M-HC1)⁺, Purity by UPLC: 99.33%.

Example 69

N,N-diethyl-2-fluoro-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide

¹H NMR (DMSO-d6, δ ): 7.95-8.04 (m, 2H), 7.42-7.46 (m, 2H), 7.08-7.10 (brt, 1H), 7.03 (s, 1H), 3.44-3.51 (m, 4H), 3.17-3.22 (m, 2H), 1.41-1.85 (m, 10H), 1.15-1.19 (t, 3H), 1.02-

1.06 (t, 3H).

Example 70

N,N-diethyl-2-fluoro-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.02-8.04 (m, 2H), 7.96 (d, J = 5.6 Hz, 1H), 7.43-7.46 (m, 2H), 7.13-7.15 (brd, 1H), 7.06 (s, 1H), 3.48-3.51 (m, 6H), 3.17-3.20 (m, 2H), 2.64- 2.67 (m, 6H), 1.84-1.88 (m, 2H), 1.76 (br, 4H), 1.15-1.17 (t, 3H), 1.02-1.06 (t, 3H).

Example 71 3-chloro-N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide.

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.41 (d, J = 4.4 Hz, 1H), 7.74-7.79 (brt, 2H), 7.53-7.58 (m, 2H), 7.13 (s, 1H), 2.9-4.0 (m, 21H), 1.8-2.5 (m, 6H ), 1.0-1.14 (m, 6H).

Example 72

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-morpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ): 7.83-7.95 (m, 3H), 7.48-7.52 (t, 1H), 7.44 (d, J = 5.6 Hz,

1H), 6.96-6.99 (m, 2H), 3.3-3.7 (m, 8H), 2.92-2.95 (brd, 2H ), 2.3-2.6 (m, 10H), 2-2.2 (m, 1H), 1.3-1.8 (m, 8H), 0.9-1.1 (m, 6H). Example 73

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 7.8 (d, J = 5.2 Hz, 1H), 7.73-7.76 (m, 2H), 7.54-7.58 (brt, 1H), 7.45 (d, J = 5.6 Hz, 1H), 6.88 (s, 1H), 3.75 (s, 2H), 3.50-3.54 (m, 2H), 2.59-2.65 (m, 4H ), 2.50-2.55 (m, 6H), 1.95-1.98 (brt, 2H), 1.64-1.69 (m, 4H), 1.51-1.52 (brd, 2H), 1.12-1.16 (m, 6H).

Example 74 (2-fluoro-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)(morpholino)methanone

¹H NMR (δ ppm) (DMS0-d6, δ ): 8.02-8.06 (m, 2H), 7.96-7.99 (m, 1H), 7.51 (brt, 1H),

7.45 (d, J = 5.2 Hz, 1H), 7.02 (brs, 2H), 3.33-3.67 (m, 14H), 2.86-2.89 (brd, 2H ), 2.4-2.43 (m, 2H), 1.67-1.92 (m, 13H).

Example 75 4-(7-((3-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-

5-yl)-N,N-diethyl-2-fluorobenzamide

¹H NMR (δ ppm) (DMSO-d6, δ ): 7.95-8.03 (m, 2H), 7.42-7.46 (m, 2H), 7.1-7.2 (m, 2H), 3.2-3.5 (m, 8H), 2.3-2.5 (m, 8H), 1.5-1.9 (m, 6H), 0.9-1.2 (m, 6H).

Example 76

N,N-diethyl-3-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide

¹H NMR (DMSO-d6, δ ): 8.36-8.37 (m, 1H), 7.95-8.06 (m, 2H), 7.58-7.74 (m, 3H), 7.1 (s,

1H), 2.8-3.9 (m, 12H), 1.3-2.2 (m, 8H), 0.9-1.2 (m, 6H).

Example 77

(2-fluoro-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)(morpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.4-8.5 (m, 1H), 8.0-8.2 (m, 2H), 7.13-7.16 (brd, 1H), 3.6-3.8 (m, 13H), 1.83-2.33 (m, 6H), 1.07-1.23 (m, 6H).

Example 78 3-(7-((3-(7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-N,N- diethylbenzamide

¹H NMR (δ ppm) (DMSO-d6, δ): 8.3-8.4 (m, 1H), 7.8-8.2 (m, 2H), 7.5-7.7 (m, 3H), 7.0 (s, 1H), 2.8-3.8 (m, 14H), 1.5-2.1 (m, 10H), 0.9-1.3 (m, 6H).

Example 79

3-(7-((3-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-

5-yl)-N,N-diethylbenzamide

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.4-8.5 (brs, 1H), 7.5-8.2 (m, 4H), 7.03-7.15 (m, 2H), 2.8-3.6 (m, 16H), 2.3-2.4 (m, 2H), 1.8-2.1 (m, 4H), 0.9- 1.3 (m, 6H).

Example 80 5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.29 (m, 1H), 8.13-8.15 (m, 1H), 7.90-7.92 (brd, 2H), 7.55-7.56 (brd, 1H), 7.17 (s, 1H), 4.5-4.6 (m, 2H), 3.0-3.6 (m, 12H), 1.8-2.2 (m, 6H), 1.2- 1.4 (m, 6H).

Example 81

5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(4-phenylpiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.29-8.35 (m, 2H), 8.12-8.14 (m, 1H), 7.95-7.97 (m, 1H), 7.60 (s, 1H), 7.27-7.35 (m, 6H), 4.5-4.6 (brd, 2H), 2.8-3.8 (m, 13H), 1.7-2.3 (m, 6H), 1.3- 1.4 (m, 6H).

Example 82 2-chloro-N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide

¹H NMR (δ ppm) (DMSO-d6, δ): 8.23 (d, J = 1.6 Hz, 1H), 8.12-8.14 (m, 1H), 7.96 (d, J = 5.2 Hz, 1H), 7.44-7.47 (m, 2H), 7.10 (brs, 1H), 7.03 (s, 1H), 3.5-3.6 (m, 3H), 3.1-3.3 (m, 3H), 2.33-2.34 (m, 6H), 1.7-1.8 (m, 2H), 1.41-1.57 (m, 6H), 1.16-1.20 (m, 3H), 1.01-1.05

(t, 3H)

Example 83

2-chloro-N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide

¹H NMR (δ ppm) (DMSO-d6, δ): 8.14 (brs, 1H), 7.81-7.92 (brm, 1H), 7.40-7.49 (m, 2H), 7.1 (s, 1H), 2.9-4.0 (m, 17H), 1.7-2.4 (m, 10H), 1.1-1.3 (m, 6H).

Example 84

4-(7-((3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)-2-chloro-N,N-diethylbenzamide

¹H NMR (δ ppm) (DMSO-d6, δ ): 8.22 (d, J = 1.6 Hz, 1H), 8.13 (d, J = 8 Hz, 1H), 7.96-

7.97 (t, 2H), 7.43-7.46 (m, 2H), 7.10 (brs, 1H), 7.02 (s, 1H), 3.30-3.56 (m, 8H), 3.1-3.2 (m, 2H), 2.37-2.45 (m, 4H), 1.82 (brs, 2H), 1.39-1.56 (m, 10H), 1.16-1.20 (t, 3H), 1.01-

1.05 (t, 3H)

Example 85

5-(3-((diethylamino)methyl)phenyl)-N-(3-(hexahydrocyclopenta[c]pyrrol-2(1H)- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (DMSO-d6, δ ): 7.9-8.0 (m, 1H), 7.4-7.5 (m, 3H), 6.9-7.0 (m, 2H), 3.5- 3.7 (m, 6H), 1.3-1.7 (m, 10H), 0.9-1.0 (m, 6H).

Example 86

(2-chloro-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ): 8.24 (d, J = 1.2 Hz, 1H), 8.14-8.16 (m, 1H), 7.97 (d, J = 5.2 Hz, 1H), 7.45-7.50 (m, 2H), 7.11 (brs, 1H), 7.03 (s, 1H), 3.19-3.71 (m, 10H), 2.33- 2.45 (m, 6H), 1.23-1.83 (m, 8H)

Example 87 (2-chloro-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ): 8.24 (d, J = 1.2 Hz, 1H), 8.14-8.16 (m, 1H), 7.95 (d, J =

5.6 Hz, 1H), 7.45-7.50 (m, 2H), 7.77-7.19 (brt, 1H), 7.05 (s, 1H), 3.51-3.71 (m, 8H), 3.18- 3.25 (m, 2H), 2.3-2.7 (m, 6H), 1.80-1.91 (m, 2H), 1.74 (brs, 4H).

Example 88

(3-chloro-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(thiomorpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ ): 7.97 (d, J = 5.2 Hz, 1H), 7.59-7.64 (m, 2H), 7.40-7.45 (m, 2H), 7.05-7.08 (t, 1H), 6.67 (s, 1H), 3.89 (brs, 2H), 3.55-3.56 (brd, 6H), 2.89-2.92 (brd, 2H), 2.51 (brs, 6H), 2.33-2.42 (m, 6H), 2.09 (brs, 1H), 1.67-1.83 (m, 6H ), 1.35-1.38 (m, 2H).

Example 89

(3-chloro-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(thiomorpholino)methanone

¹H NMR (δ ppm) (DMSO-d6, δ): 7.96 (d, J = 5.2 Hz, 1H), 7.60-7.64 (brt, 2H), 7.40-7.45 (m, 2H), 7.20 (brs, 1H), 6.69 (s, 1H), 3.89 (brs, 2H), 3.60 (brs, 2H), 3.46 (brs, 2H), 2.67 (brs, 6H), 2.33 (brs, 4H), 1.67-1.81 (t, 2H ), 1.67 (brs, 4H). EXAMPLE 90

2-chloro-N,N-diethyl-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide

¹HNMR (δ ppm) (DMSO-d₆): 8.2 (d, J = 1.6 Hz, 1H), 8.12 (d, J = 8.0 Hz,1H), 7.94 (d, J = 5.6 Hz,1H), 7. 46-7.44 (m, 2H), 7.17 (m,1H), 7.01 (s, 1H), 3.49 (q, = 6.4 Hz, , J₂=

12 Hz 2H), 3.2-3.1 (m, 2H), 2.57-2.46 (m,8H),1.83 (t, J= 6.8 Hz, 2H), 1.73 (m,4H), 1.18 (t, J = 4.8 Hz, 3H), 1.03 (t, J = 7.2 Hz,3H). ESI-MS ( m/z) 412 (M+)⁺.

EXAMPLE 91 5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(4-ethylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆): 8.10 (d, J= 2.0 Hz, 1H), 8.03 (d, J= 8 Hz, 1H), 7.95 (d, J = 5.2 Hz, 1H), 7.6 (d, J = 8 Hz, 1H), 7.45 (d, J = 5.2Hz, 1H),7.0- 7.95 (m, 2H), 3.65 (s,2H),

3.48-3.43 (m,2H), 2.58-2.51 (m, 6H), 2.48-2.40 (m, 10H).1.82- 1.75 (m,2H), 1.08-0.97 (m,9H), ;ESI-MS ( m/z) 500(M+)⁺.

EXAMPLE 92 N-(3-(4-aminopiperidin-1-yl)propyl)-5-(4-methoxyphenyl)thieno[3,2-b]pyridin-7- amine trihydrochloride

¹H NMR (δ ppm) (DMSO-d₆): 14.3 (bs, 1H ), 11.02(bs,1H ), 9.02 (bs,1H ), 8.35 (m,3H ), 8.07 (d, J = 8.4 Hz, 2H), 7.7 (d, J= 5.6 Hz, 1H), 7.2 (d, J= 8.4 Hz, 2H), 7.11-4.08 (m, 1H), 3.8 (s, 3H), 3.73-3.53 (m, 5H), 3.12-2.96 (m, 4H), 2.17-1.97 (m.6H) ;ESI-MS ( m/z) 397 (M+H)⁺.

EXAMPLE 93

5-(4-methoxyphenyl)-N-(3-(4-(methylsulfonyl)piperidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine

¹ HNMR (δ ppm) (DMSO-d₆): 8.05 (d, J = 8.8 Hz, 2H), 7.8 (d, J = 5.6 Hz, 1H), 7.4 (d, J = 5.2 Hz, 2H),7.02 (d, J = 8.8 Hz, 2H), 6.88 (s, 1H), 6.83 (m, 1H), 3.8 (s, 3H), 3.44-3.41 (m, 2H), 3.06-3.04 (m,3H), 2.93(s,3H), 2.46-2.43(m,2H), 2.01-1.90 (m,4H), 1.84-1.80 (m,2H),1.71-1.61 (m,2H). ;ESI-MS ( m/z) 460 (M+H)⁺.

EXAMPLE 94 (4-methylpiperazin-1-yl)(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin- 5-yl)phenyl)methanone

¹HNMR (δ ppm) (DMSO-d₆): 8.15 (d, J = 8.4 Hz, 2H), 7.94 (d, J = 5.6 Hz, 1H), 7.49-7.44 (m, 3H),7.07 (t, J= 5.2 Hz, 1H), 6.89 (s, 1H), 3.62 (m,2H), 3.47-3.4 (m,4H), 2.43-2.33 (m, 10H), 2.21 (s, 3H), 1.82-1.54 (m, 6H), 1.41-1.37 (m, 2H) ;ESI-MS ( m/z) 478 (M+H)⁺.

EXAMPLE 95

5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(4-methylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆): 8.12 (d, J = 5.6 Hz, 1H), 8.02 (d, J = 8 Hz, 1H), 7.95 (d, J =

5.2 Hz, 1H), 7.62 (d, J = 8 Hz, 1H), 7.45 (d, J = 5.6 Hz, 1H), 6.97 (s, 1H), 6.94 (m, 1H), 3.66 (s,2H), 3.48-3.43 (m,2H), 2.67-2.51 (m, 6H),2.46-2.33(m, 8H).2.1 (s,3H), 1.82 (t, J = 6.4Hz, 2H),1.01 (t, J = 6.8Hz, 6H) ;ESI-MS ( m/z) 486 (M+)⁺.

EXAMPLE 96

(3-chloro-4-(7-((3-(4-methylpiperazin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone

¹HNMR (δ ppm) (DMSO-d₆): 7.96 (d, J = 9.2 Hz, 1H), 7.64-7.60 (m,2H), 7.46(dd, J₁ = 1.6 Hz, J₂= 1.2Hz,1H), 7.41(d, J= 5.2Hz, 1H), 7.03(t, J = 5.2 Hz, 1H), 6.65 (s,1H), 3.63- 3.35 (m, 10H), 2.38-2.15 (m,10H), 2.11 (s, 3H), 1.76 (t, J = 8.0Hz, 2H) ;ESI-MS ( m/z) 520 (M+H)⁺. EXAMPLE 97

8-(3-((5-(4-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1- oxa-8-azaspiro[4.5]decan-2-one

¹HNMR (δ ppm) (DMSO-d₆): 8.03 (d, J= 8.4 Hz, 2H), 7.93 (d, J= 5.6 Hz, 1H), 7.44-7.39

(m, 3H), 6.94 (s, 2H), 3. 60(t, J = 4.4 Hz, 4H), 3.52 (m, 4H), 3.45-3.34 (m, 4H),2.67-

2.56(m,6H), 2.46-2.38 (m,6H), 2.02- 1.81 (m,8H); ESI-MS ( m/z) 514 (M+)⁺.

EXAMPLE 98

5-(4-methoxyphenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆): 8.04 (d, J= 8.8 Hz, 2H), 7.89 (d, J= 5.2 Hz, 1H), 7.4 (d, J

= 5.2 Hz, 1H), 7.05-7.0 (m, 3H), 6.9 (s, 1H), 3. 82 (s, 3H).3.45 (t, J = 6.4 Hz, 2H), 2.57- 2.47 (m, 6H), 1.86 -1.74 (m, 6H); ESI-MS ( m/z) 368 (M+H)⁺ .

EXAMPLE 99 N-(3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)-5-(4-methoxyphenyl)thieno[3,2- b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆): 8.04 (d, J= 8.8 Hz, 2H), 7.91 (d, J= 5.2 Hz, 1H), 7.41 (d, J = 5.2 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H), 6.88 (s, 1H), 3. 81 (s,3H), 3.8-3.45 (m, 2H), 3.29- 3.21 (m, 4H), 2.67-2.53 (m,5H), 2.33-2.09 (m,2H), 1.86-1.83 (m,2H), 1.02-0.9 (m,4H);ESI- MS ( m/z) 487 (M+H)⁺.

EXAMPLE 100 N-(3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)-5-(4-(morpholinomethyl) phenyl)thieno[3,2-b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆): 8.03 (d, J= 8.4 Hz, 2H), 7.93 (d, J= 5.6 Hz, 1H), 7.43 - 7.38(m, 3H), 7.03(t, J = 5.2 Hz, 1H), 6.09 (s, 1H),3. 59(t, J= 4.4 Hz, 4H), 3.54 -3.41(m, 8H), 2.43 (t, J = 6.4 Hz 2H),2.4-2.37(m,8H),1.81(t, J= 6 Hz, 2H), 1.54(t, J = 5.2 Hz, 4H), 1.40(t, J = 5.2 Hz, 4H) ; ESI-MS ( m/z) 521 (M+H)⁺

EXAMPLE 101

(4-(7-((3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone

¹HNMR (δ ppm) (DMSO-d₆): 8.16 (d, J= 8.4 Hz, 2H), 7.94 (d, J= 5.2 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H),7.45 (d, J = 5.2 Hz, 1H), 7.0 (s, 1H), 6.92 (t, J= 5.2 Hz, 1H), 3.63-3.45 (m,10H), 3.2-3.1 (m, 4H), 2.61-2.54 (m,4H), 2.45-2.35 (m,3H), 1.84(t, J = 5.6Hz, 2H),1.0- 0.9(m,4H) ; ESI-MS ( m/z) 570 (M+H)⁺ EXAMPLE 102 N-(3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-(morpholinomethyl) phenyl) thieno[3,2-b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆): 8.34 (d, J= 8.0 Hz, 2H), 7.91 (d, J= 5.2 Hz, 1H), 7.43 - 7.39(m, 3H), 6.99(t, J = 5.2 Hz, 1H), 6.92 (s, 1H),3. 69(t, J= 6.4 Hz, 2H), 3.6-3.55 (m, 4H), 3.52-3.43 (m, 4H), 2.53-2.38(m, 10H),1.86-1.79(m, 4H), 1.65-1.57 (m, 6H) ; ESI-MS ( m/z) 507 (M+H)⁺

EXAMPLE 103 N-(3-(piperidin-1-yl)propyl)-5-(thiophen-3-yl)thieno[3,2-b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆): 8.14-8.13 (m, 1H), 7.9 (d, J = 2.8 Hz, 1H), 7.79-7.77 (dd, = 1.2 Hz, J₂= 5.2 Hz 1H), 7.61-7.59(q, J = 2.8 Hz, 4.8Hz, 1H), 7.4 (d, J = 5.6 Hz, 1H),6.98. 69(t, J= 4.8 Hz, 1H), 6.90 (s, 1H), 3.44-3.40(q, J = 6.4 Hz, 8.0Hz 2H), 2.41- 2.21 (m, 6H),1.85-1.78(m,2H),l.58-1.54(m,4H), 1.41-1.3(m,2H); ESI-MS ( m/z) 358 (M+H)⁺

EXAMPLE 104

5-phenyl-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine

¹HNMR (δ ppm) (DMSO-d₆):8.09 (d, J = 8.8 Hz, 2H),7.93 (d, J = 5.6 Hz, J₂= 5.2 Hz 1H),7.49 -7.39(m, 4H), 7.04-7.02 (t, J = 5.6 Hz, 1H),6.93 (s, 1H), 3.46-3.36(m, 2H), 2.40- 2.38 (m, 6H),1.85-1.78(m,2H),l.58-1.55(m,4H), 1.41-1.3(m,2H) ; ESI-MS ( m/z) 352 (M+H)⁺

Example 105

N-(3-(4-methylpiperazin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno

[3,2-b]pyridin-7-amine

¹H NMR (δ ppm) (In DMSO) : 8.02 (d, J = 8.4Hz, 2H), 7.92 (d, J = 5.2Hz, 1H), 7.43 - 7.37 (m, 3H), 6.93 (s, 1H), 6.88 (s, 1H), 3.55 (s, 2H), 3.44 - 3.43 (m, 2H), 2.67 - 2.62 (m, 9H), 2.17 (m, 3H), 1.81 (m, 2H); LC-MS: 481.7 (M)⁺, Purity by UPLC: 94.59%.

Example 106

5-(4-(morpholinomethyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine

¹HNMR (δ ppm) (DMSO-d6): 8.03 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 5.6 Hz, 1H), 7.44-7.39 (m, 3H), 6.92 (s, 1H), 3.60-3.58 (m, 4H), 3.52 (s, 2H), 3.46-3.41 (q, 2H), 2.38 (m,10H), 1.83 (q, 4H), 1.57-1.42 (m, 2H); ESI-MS ( m/z) 451 (M+H)+ .

Example 107 5-(4-(morpholinomethyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7- amine trihydrochloride.

¹HNMR (δ ppm) (DMSO-d6): 14.67 (bs, 1H), 11.9 (bs, 1H), 10.6 (bs, 1H), 9.1 (bs, 1H), 8.38 (d, J = 5.6 Hz, 1H), 8.20 (d, J = 4.8 Hz, 2H), 7.94 (d, J = 8.0 Hz, 2H), 7.7 (d, J = 5.6

Hz, 1H), 7.2 (s, 1H), 4.47 (m, 2H), 4.02-3.7 (m, 6H), 3.49-3.43 (m, 2H), 3.24-3.12 (m, 6H), 2.93-2.88 (m, 2H), 2.18-2.15 (m, 2H), 1.89-1.86 (m, 6H); ESI-MS ( m/z) 451 (M+H)+ .

Example 108 N-cyclopropyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide

1H-NMR (δ ppm) (In DMSO) : δ 8.51 (d, J = 4Hz, 1H), 8.15 (d, J= 8.4Hz, 2H), 7.91 - 7.96 (m, 3H), 7.46 (d, J = 5.6Hz, 1H), 6.97-7.01 (m, 2H), 3.55-3.57 (m, 4H), 3.43-3.48 (m, 2H), 2.85 - 3.17 (m, 3H), 2.38 - 2.51 (m, 6H), 2.07-2.13 (m, 1H), 1.71-1.81 (m, 6H),

1.39-1.47 (m, 2H), 0.58-0.74 (m, 4H);

The following compounds can be prepared by following the general scheme 1 and the process described in Example 1 above, including their suitable modifications well within the scope of a skilled person: N,N-diethyl-4-(4-((3-(piperidin-1-yl)propyl)amino)-1H-pyrrolo[2,3-b]pyridin-6-yl) benzamide;

N,N-diethyl-4-(4-((3-morpholinopropyl)amino)-1H-pyrrolo[2,3-b]pyridin-6-yl) benzamide;

N,N-diethyl-4-(4-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)-1H-pyrrolo[2,3-b] pyridin-6-yl)benzamide;

N,N-diethyl-4-(4-((3-(piperidin-1-yl)propyl)amino)-6,7-dihydro-5H-cyclopenta[b] pyridin-2-yl)benzamide;

N,N-diethyl-4-(4-((3-(piperidin-1-yl)propyl)amino)thieno[2,3-b]pyridin-6-yl)benzamide; morpholino(4-(7-((3-(piperidin-1-yl)propyl)amino)furo[3,2-b]pyridin-5-yl)phenyl) methanone;

N,N-diethyl-4-(4-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-d]pyrimidin-2-yl) benzamide;

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thiazolo[5,4-b]pyridin-5-yl) benzamide;

N,N-diethyl-4-(4-((3-(piperidin-1-yl)propyl)amino)isothiazolo[5,4-b]pyridin-6-yl) benzamide;

N,N-diethyl-4-(4-((3-(piperidin-1-yl)propyl)amino)-1H-pyrazolo[3,4-b]pyridin-6-yl) benzamide;

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)oxazolo[5,4-b]pyridin-5-yl) benzamide;

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)oxazolo[4,5-b]pyridin-5-yl) benzamide;

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thiazolo[4,5-b]pyridin-5-yl) benzamide;

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)isothiazolo[4,5-b]pyridin-5-yl) benzamide;

N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)-1H-pyrazolo[4,3-b]pyridin-5-yl) benzamide; N,N-diethyl-4-(2-methyl-7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl) benzamide;

N,N-diethyl-4-(6-methyl-7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl) benzamide;

N,N-diethyl-4-(3-methyl-7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl) benzamide;

5-(4-(2-(piperidin-1-yl)propan-2-yl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b] pyridin-7-amine;

5-(4-( 1 -(piperidin-1-yl)cyclopropyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b] pyridin-7-amine;

5-(3-fluoro-4-(l -thiomorpholinocycloprop yl)phenyl)-N-(3-(piperidin-1-yl) propyl)thieno[3 ,2-b]pyridin-7-amine ;

5-(3-fluoro-4-(2-thiomorpholinopropan-2-yl)phenyl)-N-(3-(piperidin-1-yl) propyl)thieno[3,2-b]pyridin-7-amine.

Biological Activity:

In-Vitro LMPTP enzyme assay screening details

Potential LMW-PTP A inhibitors were routinely screened in a cell free phosphatase assay. Briefly, 100 nM of GST tagged full length recombinant human LMW-PTP A was incubated in black round bottom 96 well assay plate with increasing concentration of 1X NCEs (diluted from 100X stock in 100% DMSO) and 400 μM of OMFP (3-O- Methylfluorescein phosphate) substrate in assay buffer (500 mM Tris, pH 6.0; 0.1% Triton X-100; 10 mM DTT) for 15 min at room temperature. Total volume of reaction was kept 50 μl. After 10 minutes of incubation, fluorescence was measured with an excitation and emission wavelength of 485 and 535 nm respectively in Tecan MPro 1000. Data were plotted taking No inhibitor control set as the 100% phosphatase activity. For dose response curve % phosphatase activity was plotted against cone on Log scale and IC50 was determined by nonlinear curve fitting method using GraphPad Prism software 6. In-vitro assays:

Table 1: In -vitro LMPTP inhibition IC50 in the enzyme assay

Compounds of the present invention are having no CYP liability and show less than 50 %

5 inhibition for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 & CYP3A4 @ 10 μM. Compounds are in vitro metabolically stable in the human microsomal enzymes and possess satisfactory oral bioavailability in the rodents. The compounds 6, 15, 32, 39, 41, 43, 44, 53, 72, 95, 98 & 107 exhibited significant reduction [20-50%] in fasting glucose and HOMA-IR [22-75%] in diet induced obese mice.

In one of the embodiments compound of formula (I) of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients by techniques and processes and concentrations as are well known.

The compounds of formula (I) or pharmaceutical compositions containing them are useful as a medicament for the inhibition of LMPTP expression and suitable for humans and other warm blooded animals, and may be administered either by oral, topical or parenteral administration.

Thus, a pharmaceutical composition comprising the compounds of the present invention may comprise a suitable binder, suitable bulking agent &/or diluent and any other suitable agents as may be necessary. Optionally, the pharmaceutical composition may be suitably coated with suitable coating agents.

In one of the embodiments compound of formula (I) of the present invention may be used in combination with one or more suitable pharmaceutically active agents selected from following therapeutic agents in any combination. Compound of formula (I) may appropriately combined with FXR agonist and semi-synthetic bile acid analogue, ACC inhibitor, Dual CCR2 and CCR5 antagonist, Thyroid hormone receptor beta agonist, MAPK5/ ASK-1 inhibitor, SGLT-2 inhibitor, Glucagon-like peptide- 1 (GLP-1) receptor agonist, PPAR α/δ agonist, Stearoyl Coenzyme A Desaturase 1 (SCD1) inhibition- Synthetic fatty acid-bile acid conjugate, Caspase inhibitor, metformin, DPP4, insulin sensitizer, Bempedoic acid or pharmaceutically acceptable salts thereof..

While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Claims

We claim:

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

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

‘A’ is selected from the following rings:

‘X’ & ‘Y’ at each occurrence is independently selected from N or CR wherein R is selected from H, -CO, optionally substituted group selected from (C₁-C₆)alkyl;

‘Z’ is independently selected from a covalent bond, -O-, -NR₁, -NR₁C(O)-, - C(O)NR₁-, -OC(O)- or -C(O)-O-, where R₁ may optionally selected from cycloalkyl, heterocyclic, heteroaryl, fused heterocycle bicyclic ring, spiro or bridged system;

‘T’ is independently a bond, optionally substituted group selected from (C₁- C₆)alkyl, (C₂-C₆)alkylene, (C₂-C₆)alkyne, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene; In an embodiment ‘T’ may be absent;

R¹ & R² at each occurrence is independently selected from hydrogen, -NR⁵R⁶, OR⁷, SR , substituted or unsubstituted groups selected from (C₁-C₆)alkyl, heteroalkyl, (C₃-C₇)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro or bridged cyclic system; each of R³ & R⁴ at each occurrence is independently selected from hydrogen, halogen, haloalkyl optionally substituted group selected from (C₁-C₆)alkyl or (C₃- C₇)cycloalkyl;

R⁵, R⁶ & R⁷ at each occurrence is independently selected from hydrogen, haloalkyl optionally substituted group selected from (C₁-C₆)alkyl or (C₃-C₇)cycloalkyl.

2. The compound of formula (I) as claimed in claim 1, wherein ‘A’ is selected from the following rings:

3. The compound as claimed in any preceding claim, wherein when any of the group is substituted, the substitutions are selected from hydrogen, hydroxy, cyano, halo, haloalkyl, haloalkyloxy, alkyl thio optionally substituted group selected from (C₁- C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₃-C₇)cycloalkyl, (C₁-C₆) alkoxy, -COR₁₂, -CSR₁₂, C(O)OR₁₂, C(O)-R₁₂, -C(O)-NR₁₂R₁₃, -C(S)-NR₁₂R₁₃, -SO2R₁₂ group, wherein each of R₁₂ and R₁₃ is independently selected from hydrogen, optionally substituted group selected from (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-Ce)alkynyl, (C₃- C₇)cycloalkyl, aryl, heteroaryl, heterocyclyl groups.

4. Compound of general formula (I) as claimed in claim 1, wherein compound is selected from: 1-(3-((5-(4-(diethylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-4-

( 114-pyrrolidin-2-ylium-1-yl)- 114-piperidin-2-ylium chloride hydrochloride; 5-(4-((diethylamino)methyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine ;

4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)- N,N-diethylbenzamide dihydrochloride; N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine trihydrochloride ;

N-(3-(piperidin-1-yl)propyl)-5-(4-(pyrrolidin-1-ylmethyl)phenyl)thieno[3,2- b]pyridin-7-amine ;

N-(3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)-5-(4-

((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-amine;

8-(3-((5-(4-(piperidine-1-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)- 1-oxa-8-azaspiro[4.5]decan-2-one; piperidin-1-yl(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)methanone;

8-(3-((5-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7- yl)amino)propyl)-1-oxa-8-azaspiro[4.5]decan-2-one;

(4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(morpholino)methanone; morpholino(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)methanone;

4-(7-((3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)- N,N-diethylbenzamide;

4-(7 -((3 -(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)-N,N-diethylbenzamide;

4-(7-((3-(4-(cyclopropylsulfonyl) piperazin- 1-yl) propyl) amino)thieno[3,2- b]pyridin-5-yl)-N,N-diethylbenzamide; pyrrolidin-1-yl(4-(7 -((3 -(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3 ,2- b]pyridin-5-yl)phenyl)methanone;

85 1-(2-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)ethan-1-one;

5-(4-methoxyphenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

(4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)( 1 -oxidothiomorpholino)methanone;

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-thiomorpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine; thiomorpholino(4-(7-((3-(4-thiomorpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone;

( 1 -oxidothiomorpholino)(4-(7-((3 -thiomorpholinopropyl)amino)thieno [3 ,2- b]pyridin-5-yl)phenyl)methanone;

N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)-5-(4-(trifluoromethyl)phenyl) thieno[3,2-b]pyridin-7-amine;

N-(3-thiomorpholinopropyl)-5-(4-(trifluoromethyl)phenyl)thieno[3,2-b]pyridin-7- amine;

N-(3-(piperidin-1-yl)propyl)-5-(4-(trifluoromethyl)phenyl)thieno[3,2-b]pyridin-7- amine;

N-(3-(4-morpholinopiperidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl) thieno[3,2-b]pyridin-7-amine;

N-(3-(pyrrolidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno[3,2- b]pyridin-7-amine ;

N-(3-(piperidin-1-yl)propyl)-5-(4-(thiomorpholinomethyl)phenyl)thieno[3,2- b]pyridin-7-amine ;

N-(3-morpholinopropyl)-5-(4-(1-(pyrrolidin-1-yl)ethyl)phenyl)thieno[3,2-b]pyridin- 7-amine; 5-(4-(1-(pyrrolidin-1-yl)ethyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine ;

N-(3-(piperidin-1-yl)propyl)-5-(4-(1-(pyrrolidin-1-yl)ethyl)phenyl)thieno[3,2- b]pyridin-7-amine ; morpholino(4-(7-((4-(4-(pyrrolidin-1-yl)piperidin-1-yl)butan-2-yl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone;

5-(4-( 1 -(piperidin-1-yl)ethyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine ;

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-methylpiperazin-1-yl)propyl) thieno[3,2-b]pyridin-7-amine;

(4-(7 -((3 -(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)amino) thieno[3,2-b]pyridin-5-yl)phenyl)(thiomorpholino)methanone; tri-hydrochloride salt of N-(3-(piperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl) phenyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-morpholinopiperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl)phenyl) thieno[3,2-b]pyridin-7-amine;

(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)phenyl)

(thiomorpholino)methanone ;

(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

N, N-dimethyl-4-(7-((3-(2-oxo-1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino) thieno [3 ,2-b]pyridin-5 -yl)benzamide ; 4-(7-((3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-

N,N-dimethylbenzamide;

8-(3-((5-(4-((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)- 1-oxa-8-azaspiro[4.5]decan-2-one;

N-(3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-((diethylamino)methyl)phenyl) thieno[3,2-b]pyridin-7-amine;

N-(3-(piperidin-1-yl)propyl)-5-(4-(piperidin-1-ylmethyl)phenyl)thieno[3,2- b]pyridin-7-amine ;

N-(3-(2-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-((diethylamino)methyl)phenyl) thieno[3,2-b]pyridin-7-amine;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine ;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(4-morpholinopiperidin-1-yl)propyl) thieno[3,2-b]pyridin-7-amine;

5-(4-((diethylamino)methyl)phenyl)-N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl) thieno[3,2-b]pyridin-7-amine;

N-(3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)-5-(4-(pyrrolidin-1-ylmethyl)phenyl) thieno[3,2-b]pyridin-7-amine;

N-(3-(4-(4-(cyclopropylsulfonyl)piperazin-1-yl)piperidin-1-yl)propyl)-5-(4-

((diethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-amine; trihydrochloride salt of N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide; dihydrochloride salt of N,N-diethyl-4-(7-((3-((3aR,6aS)-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide;

N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide; N,N-diethyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

4-(7-((3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)-N,N-diethylbenzamide dihydrochloride;

N,N-diethyl-2-fluoro-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

3-chloro-N,N-diethyl-4-(7-((3-(4-morpholinopiperidin-1- yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)benzamide;

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-morpholinopiperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(piperidin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

(2-fluoro-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)(morpholino)methanone;

4-(7-((3-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-

5-yl)-N,N-diethyl-2-fluorobenzamide;

N,N-diethyl-3-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

3-(7-((3-(7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin-5-yl)-N,N- diethylbenzamide ;

3-(7-((3-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)propyl)amino)thieno[3,2-b]pyridin- 5-yl)-N,N-diethylbenzamide; 5-(3-chloro-4-((diethylamino)methyl)phenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno [3,2-b]pyridin-7-amine;

2-chloro-N,N-diethyl-4-(7-((3-(4-(pyrrolidin-1-yl)piperidin-1- yl)propyl)amino)thieno [3,2-b]pyridin-5-yl)benzamide;

(3-chloro-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-

5-yl)phenyl)(thiomorpholino)methanone;

(3-chloro-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)phenyl)(thiomorpholino)methanone;

2-chloro-N,N-diethyl-4-(7-((3-(pyrrolidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide;

N-(3-(4-aminopiperidin-1-yl)propyl)-5-(4-methoxyphenyl)thieno[3,2-b]pyridin-7- amine trihydrochloride;

5-(4-methoxyphenyl)-N-(3-(4-(methylsulfonyl)piperidin-1-yl)propyl)thieno[3,2- b]pyridin-7-amine ;

(4-methylpiperazin-1-yl)(4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)phenyl)methanone; 5-(4-((diethylamino)methyl)-3-fluorophenyl)-N-(3-(4-methylpiperazin-1- yl)propyl)thieno[3,2-b]pyridin-7-amine;

8-(3-((5-(4-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-yl)amino)propyl)-1- oxa-8-azaspiro[4.5]decan-2-one;

5-(4-methoxyphenyl)-N-(3-(pyrrolidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)-5-(4- methoxyphenyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(3-oxa-9-azaspiro[5.5]undecan-9-yl)propyl)-5-(4-(morpholinomethyl)phenyl) thieno[3,2-b]pyridin-7-amine;

(4-(7-((3-(4-(cyclopropylsulfonyl)piperazin-1-yl)propyl)amino)thieno[3,2-b]pyridin- 5-yl)phenyl)(morpholino)methanone;

N-(3-(1-oxa-8-azaspiro[4.5]decan-8-yl)propyl)-5-(4-

(morpholinomethyl)phenyl)thieno [3,2-b]pyridin-7-amine;

N-(3-(piperidin-1-yl)propyl)-5-(thiophen-3-yl)thieno[3,2-b]pyridin-7-amine;

5-phenyl-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-7-amine;

N-(3-(4-methylpiperazin-1-yl)propyl)-5-(4-

(thiomorpholinomethyl)phenyl)thieno[3 ,2-b] pyridin-7 -amine;

5-(4-(morpholinomethyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin-

7-amine trihydrochloride;

5-(4-(morpholinomethyl)phenyl)-N-(3-(piperidin-1-yl)propyl)thieno[3,2-b]pyridin- 7-amine;

N-cyclopropyl-4-(7-((3-(4-morpholinopiperidin-1-yl)propyl)amino)thieno[3,2- b]pyridin-5-yl)benzamide;

N-cyclopropyl-4-(7-((3-(piperidin-1-yl)propyl)amino)thieno[3,2-b]pyridin-5- yl)benzamide; 4-(7-((3-(4-(cyclopropylsulfonyl) piperazin-1-yl) propyl) amino)thieno[3,2- b]pyridin-5-yl)-N,N-diethylbenzamide. A pharmaceutical composition comprising a therapeutically effective amount of compound of formula (I) as claimed in any of preceding claims and suitable pharmaceutically acceptable excipients. A pharmaceutical composition comprising compounds of formula (I) in combination with one or more pharmaceutically active agents selected from group comprising FXR agonist and semi-synthetic bile acid analogue, ACC inhibitor, Dual CCR2 and CCR5 antagonist, Thyroid hormone receptor beta agonist, MAPK5/ ASK-1 inhibitor, SGLT-2 inhibitor, Glucagon-like peptide- 1 (GLP-1) receptor agonist, PPAR α/δ agonist, Stearoyl Coenzyme A Desaturase 1 (SCD1) inhibition-Synthetic fatty acid-bile acid conjugate, Caspase inhibitor, metformin, DPP4, insulin sensitizer, Bempedoic acid or pharmaceutically acceptable salts thereof. The use of compounds as claimed in any of preceding claims or their pharmaceutical compositions for the treatmen t/mitigation or regulation of metabolic disorders or other diseases or conditions mediated by low molecular weight protein tyrosine phosphatases (LMPTP). Method of treating metabolic disorders comprising the administering to a patient in need thereof an effective amount of a compound as claimed in any of above claims or pharmaceutical composition thereof.