Sting agonists and antibody drug conjugates thereof

Abstract

The present disclosure relates to a series of compounds which are agonist of the stimulator of interferon genes (STING), or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof and a process for the preparation of the same. The present disclosure also relates to antibody-drug conjugate (ADCs) comprising the STING modulators as payload, covalently linked to an antibody through a linker. The present disclosure further relates to the use of said STING modulators and their corresponding ADCs in the treatment of various diseases mediated by STING.

Description

Title of Invention: STING AGONISTS AND ANTIBODY DRUG CONJUGATESTHEREOFFIEED OF THE INVENTION

[0001] The present disclosure relates to a series of compounds which are agonist of the stimulator of interferon genes (STING), or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof and a process for the preparation of the same. The present disclosure also relates to antibody -drug conjugate (ADCs) comprising the STING modulators as payload, covalently linked to an antibody through a linker. The present disclosure further relates to the use of said STING modulators and their corresponding ADCs in the treatment of various diseases mediated by STING.BACKGROUND OF THE INVENTION

[0002] The innate immune system is the first line of defence in mammal against infection from foreign microorganisms including bacteria, viruses, parasites and other infectious threats, but it also responds to certain danger signals associated with cellular or tissue damage. The response is initiated by activation of Pattern Recognition Receptors (PRRs) that can detect different forms of foreign antigens, i.e. nucleic acids, peptides, carbohydrates, and ligands from the pathogens as well as damage associated molecular patterns (Takeuchi O. et al, Cell, 2010: 140, 805-820). Activation of PRRs leads to up-regulation of genes involved in the inflammatory response including type 1 interferons, pro-inflammatory cytokines, chemokines and anti-microbial peptides which suppress pathogen replication and facilitate adaptive immunity (Palm and Medzhitov, Immunol Rev (2009) 227:221-233; Takeuchi and Akira, Immunol Rev (2009) 227:75-86; Beutler, Blood (2009) 113: 1399-1407). A growing number of these receptors have been identified including Toll-like receptors (TLRs), C-type lectin receptors, retinoic acid inducible gene I (RIG-I)-like receptors and NOD-like receptors (NLRs) and also double stranded DNA sensors.

[0003] STING (also known as MIT A, MPYS, ERIS, and TMEM173), is one of such PRRs in the innate immune response, associated with the endoplasmic reticulum (ER) and that could detect cytosolic nucleic acids (Ishikawa and Barber, Nature (2008) 455:674-678). STING may form symmetrical dimers combined with its ligands in V- shaped conformation, while not completely covering the bound ligands. Direct bindingof STING to its ligands induces a conformational change of the complex resulting in a downstream signalling cascade involving TBK1 activation, IRF-3 phosphorylation, and production of type I IFNs and other proinflammatory cytokines, such as TNF, IL-6 and IFNs (Ishikawa and Barber, Nature (2008) 455:674-678).

[0004] Compounds that bind to STING and act as agonist have been shown to induce type 1 interferons and other cytokines on incubation with human peripheral blood mononuclear cells (PBMCs). Compounds which induce human interferons may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases, neurodegenerative disease, pre-cancerous syndromes and cancer, and may also be useful as immunogenic composition or vaccine adjuvants. Compounds that bind to STING may act as antagonists and could be useful in the treatment, for example of autoimmune diseases. It is envisaged that targeting STING with activation or inhibiting agents may be a promising approach for treating diseases and conditions in which modulation for the type 1 IFN pathway is beneficial, including inflammatory, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes and as immunogenic composition or vaccine adjuvants.

[0005] Antibody-drug conjugates (ADCs) are comprised of a drug like small molecule, covalently linked to an antibody. The antibody represents a targeting mechanism tuned to a specific site of action. Upon reaching the site, the ADC is designed to release a small molecule, the drug, allowing it to perform its designed function in a targeted manner, as opposed to diffusing systemically through the entire body of the subject. This targeted approach allows for treatment with drugs that would otherwise require doses so high as to be toxic when administered systemically and minimizes potential for on-target, off-tumor toxicity.

[0006] The ADCs of this disclosure modulate the activity of STING, and accordingly, may provide a beneficial therapeutic impact in treatment of diseases, disorders and / or conditions wherein modulation of STING is beneficial. Such examples of disease, disorder and / or conditions includes, but not limited to, inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes, and as vaccine adjuvants.

[0007] PCT international application publications nos. WO2017 / 011920, WO2017 / 175147, WO2017 / 175156, WO2018 / 234805, WO2018 / 234807,WO2018 / 234808, WO2019 / 023635, WO2019 / 027857, WO2019 / 027858, and Nature (2018), 564 (7736) :439-443, discloses STING modulators.

[0008] PCT international application publication nos. WO2023 / 059544, WO2022 / 272039, WO2022 / 155518, WO2021 / 202984, WO2021 / 202984,WO2023 / 025256, WO2022 / 086853, WO2021 / 226440, WO2021 / 026009 and US patent no. US11596692, discloses STING-antibody-drug conjugate (STING-ADCs).SUMMARY OF THE INVENTION

[0009] One aspect of the present disclosure relates to a compound of Formula I:or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-NH-R4, -NR5R6, -O-C1-6 alkyl-O-Ci-6 alkyl-CON(R7)- NH-R8and -CO-NR9R10; whereinR3is selected from hydrogen, and -Ci-6-alkyl;R4is selected from hydrogen, -C1-4 alkyl, -Ci-e alkyl-COOH, -C3-6 cycloalkyl-COOH, -Ci-6 alkyl-CONRnR12, -Ci-6-alkyl-NR13R14, and -Ci-e alkyl-OR15;R5is -Ci-e alkyl-COOH;R6is -Ci-6 alkyl-CONHNH2;R7is selected from hydrogen and -Ci-6-alkyl;R8is selected from hydrogen and -Ci-6-alkyl;R9is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R10is selected from -(CH2)I-6NH-CH2-(CHOH)I-6-CH2OH, -(CH2)I-6NH-CH2- (CHOH)I-6-COOH, -(CH2)I-6NH-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH, and -Ci-6- alkyl-COOH;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl and R17is hydrogen or -C1-3 alkyl.

[0010] In one aspect, the present disclosure relates to a compound of Formula la:or a pharmaceutically acceptable salt, stereoisomer or deuterated analog thereof; wherein:R3is selected from hydrogen, and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-e alkyl-COOH, -C3-6 cycloalkyl-COOH, - Ci-6 alkyl-CONRnR12, -Ci-6-alkyl-NR13R14, and -C1-6 alkyl-OR15;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched Ci-6 alkylene which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

[0011] In one aspect, the present disclosure relates to a compound of Formula lb,or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof; wherein p is an integer between 1-6;R3is selected from hydrogen and -Ci-4-alkyl;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched C1-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

[0012] In one aspect, the present disclosure relates to a pharmaceutical composition comprising a compound of formula I, Formula la or Formula lb and pharmaceutically acceptable excipient.

[0013] In one aspect, the present disclosure relates to a method of treating disease or disorder mediated by STING in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of Formula I, Formula la or Formula lb.

[0014] In one aspect, the present disclosure relates to use of the compound of Formula I, Formula la or Formula lb for the treatment of diseases or disorders mediated by STING.

[0015] In one aspect, the present disclosure relates to a construct of Formula C-I or Formula C-II:Formula C-I Formula C-II and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula I with a linker of Formula [-Q-A-L or, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)-, -NR5R6, -O-C1-4 alkyl-O-Ci-4 alkyl-CON(R7)-N(R8)- and -CO-NR9R10-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, C3-6-cycloalkyl-COOH, -Ci-6-alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -C1-6 alkyl-COOH;R6is -C1-6 alkyl-CONHNH-;R7' is selected from hydrogen and -C1-6 alkyl;R8is selected from hydrogen and -Ci-6 alkyl;R9' is selected from hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6- COOH)- and -(CH2)I-6N(-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl, and R17' is hydrogen or -C1-3 alkyl;Q is selected from following moieties:wherein ‘]’ denotes attachment of Q to R2’; whiledenotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q with L-4 at position #;A is a natural or non-natural amino acid or a peptide of 2 to 5 amino acids, wherein A is attached to Q through its C terminal; andL is selected from following moieties:wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0016] In one aspect, A is a peptide selected from Ala- Ala, Ala- Ala- Ala, Ala-Phe, Val-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from following moieties:Moiety A-4 wherein w is an integer selected from 1 to 24.

[0017] In one aspect, the present disclosure relates to a construct of Formula C-Ia:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula la with a linker of Formula [-Q-A-L, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH, -C3-6 cycloalkyl-COOH, -C1-6 alkyl-CONR11R12, -Ci-6-alkyl-NR1,3R’14’, and -C1-6 alkyl-OR15’;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -Cl-3 alkoxy, halogen or -NR16'R17', wherein R16’ is hydrogen or -Cl-3 alkyl, and R17’ is hydrogen or -Cl-3 alkyl;Q is selected from following moieties:whereindenotes attachment of Q to A;A is a natural or non-natural amino acid or a peptide of 2 to 5 amino acids, wherein A is attached to Q through its C terminal; andL is selected from following moietieswherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0018] In one aspect, the present disclosure relates to an antibody -drug conjugate of Formula A:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula I to an antibody via a linker U, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)-, -NR5R6-, -O-Ci-4 alkyl-O-Ci-4 alkyl- CON(R7)-N(R8)- and -CO-NR9R10-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, C3-6-cycloalkyl-COOH, -Ci-6-alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -Ci-6 alkyl-COOH;R6is -Ci-6 alkyl-CONHNH-;R7' is selected from hydrogen and -Ci-6 alkyl;R8' is selected from hydrogen and -Ci-6 alkyl;R9is selected from hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6-COOH)- and -(CH2)I-6N(CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

[0019] In one aspect, U is linker moiety with following structure:[-Q-A-L1- or , wherein Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L', while ‘)’ denotes the attachment of Q to L' at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala- Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly- Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from following moieties:Moiety A-5andMoiety A-6Moiety A-4 wherein w is an integer selected from 1-24 and A is attached to Q through its C terminal;L' is a moiety selected from:Moiety L'-4 wherein ‘** ’ is atachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0020] In one aspect, the present disclosure relates to an antibody-drug conjugate ofFormula A-I or Formula A-II:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the construct of Formula C-I or Formula C-II with a linker of Formula[-Q-A-L’ or , whereinR1is -NH2 and -NH-Ci-6-alkyl;R2is -CON(R3)-N(R4)-, -NR5R6-, -O-Ci-4 alkyl-O-Ci-4 alkyl-CON(R7')-N(R8')- and - CO-NR9R10'-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, -C3-6-cycloalkyl-COOH, -Ci-6-alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -Ci-6 alkyl-COOH;R6is -Ci-6 alkyl-CONHNH-;R7' is selected from hydrogen and -Ci-6 alkyl;R8' is selected from hydrogen and -Ci-6 alkyl;R9is selected from hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6-N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6-N(-CH2-(CHOH)I-6- COOH)-, and -(CH2)I-6-N(CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH,-CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4;Z is straight or branched -Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl, and R17' is hydrogen or -C1-3 alkyl;Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L', while ‘)’ denotes the attachment of Q to L' at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala- Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly- Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from following moieties:wherein w is an integer selected from 1-24 and A is attached to Q through its C terminal;L' is a moiety selected from:Moiety L'-4 wherein ‘**’ is atachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24; andAb is an antibody.

[0021] In one aspect, the present disclosure relates to an antibody-drug conjugate ofFormula A-Ia:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the construct of Formula C-Ia, wherein R3is selected from hydrogen and -Ci-4-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH, -C3-6 cycloalkyl-COOH, -C1-6 alkyl-CONR1 rR12', -Ci-6-alkyl-NR13R14' and -C1-6 alkyl-OR15';Rnis selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -(CH2)I-6NH-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14' is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Z is straight or branched C1-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17is hydrogen or -C1-3 alkyl;Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L1, while ‘)’ denotes the attachment of Q to L1at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala- Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly- Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -C1-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective C5 or Ce-acid derivatives,ORA is a peptide selected from following moieties:Moiety A-5andMoiety A-6Moiety A-4 wherein w is an integer selected from 1-24 and A is attached to Q through its C terminal; andL' is selected fromMoiety L'-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24; andAb is an antibody.

[0022] In one aspect, the present disclosure relates to a composition comprising an antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia and pharmaceutically acceptable excipient.

[0023] In one aspect, the present disclosure relates to a method of treating disease or disorder mediated by STING in a subject comprising administering to the subject a therapeutically effective amount of the antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia.

[0024] In one aspect, the present disclosure relates to use of an antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a disease or disorder mediated by STING.

[0025] In one aspect, the present disclosure relates to use of an antibody drug conjugate of Formula-A, Formula A-I, Formula A-II or Formula A-Ia or a pharmaceutically acceptable salt thereof, for treating a disease or disorder mediated by STING.DETAILED DESCRIPTION OF THE INVENTION

[0026] ABBREVIATIONSMai MaleimideAla / A Alanine Asp / D Aspartic acid Glu / E Glutamic acid Ser / S Serine Gly / G GlycinePhe / F Phenylalanine Val / V Valine Cit / C Citrulline PABA / PAB p-aminobenzyl alcohol EG / PEG Ethylene Glycol / Poly Ethylene Glycol NHS N-Hydroxy succinimide HATE l-[Bis(dimethylamino)methylene]-lH-l,2,3-triazolo[4,5- / | pyridinium 3-oxide hexafluorophosphateDIPEA N,N -Diisopropylethylamine DMF N,N -Dimethylformamide DIAD Diisopropyl azodicarboxylate TBTU O-(Benzotriazol- 1-yl)- N,N,N',N'-tetramethyluronium tetrafluoroborateTFA Trifluoroacetic acid ACN AcetonitrileDMSO Dimethyl sulfoxide DCM Methylene Dichloride or DichloromethaneRT Room temperature

[0027] DEFINITIONS

[0028] The term “pharmaceutically acceptable salt” as used herein includes acid addition salts formed with either organic or inorganic acids. Suitable pharmaceutically acceptable salts include, but not limited to, acid addition salts which may be salts of inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, or of organic acids such as, for example, acetic acid, benzenesulfonic acid, methane sulfonic acid, benzoic acid, citric acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, suberic acid, azelaic acid, malic acid, tartaric acid, and amino acids such as glutamic acid or aspartic acid. The pharmaceutically acceptable acid addition salts also include salts formed with the addition of one or more equivalents of acids, for example, monohydrochloride, dihydrochloride salts.

[0029] Compounds and salts described in this specification may exist in solvated forms and unsolvated forms. For example, a solvated form may be a hydrated form, such as a hemi-hydrate, a mono-hydrate, a di-hydrate, a tri-hydrate or an alternative quantity thereof.

[0030] A "Tautomer" refers to a compound that undergoes rapid proton shifts from one atom of the compound to another atom of the compound. Some of the compounds described herein may exist as tautomers with different points of attachment of hydrogen. The individual tautomers as well as mixture thereof are encompassed with compounds of Formula I. Compounds and salts described in this specification may exist as a mixture of tautomers. "Tautomers" are structural isomers that exist in equilibrium resulting from the migration of a hydrogen atom.

[0031] The term “deuterated analog” as used herein refers to compounds described herein wherein at least one hydrogen atom has been replaced by a deuterium atom. The deuterated analog may be a fully or partially deuterium substituted derivative.

[0032] The term “stereoisomers ” as used herein refers to isomers of the compounds as described herein, wherein the compounds have same molecular formula and sequence of bonded atoms, but differ in the three-dimensional spatial arrangement of atoms. The said term includes, but not limited to enantiomer, diastereomer, geometric isomerism (cis-trans and E-Z isomerism), conformational isomers (conformers) or anomers.

[0033] The term “halogen ”, as used herein includes chloro, fluoro, bromo and iodo.

[0034] The term “alkyl” as used herein refers to a saturated hydrocarbon chain radical that includes solely carbon and hydrogen atoms in the backbone, either linear or branched, having from 1 to 6 carbon atoms (“C i-ealkyF) or from 1 to 3 carbon atoms (“CisalkyF), both inclusive unless defined otherwise and which is attached to the rest of the molecule by a single bond. Suitable non-limiting examples of alkyl groups include, e.g., methyl, ethyl, w-propyl. 1-methylethyl (isopropyl), w-pcntyl. w-hcxyl. etc. Unless set forth or recited to the contrary, all alkyl groups described or claimed herein are optionally substituted.

[0035] The term “alkylene” as used herein refers to a divalent saturated hydrocarbon chain radical that includes solely carbon and hydrogen atoms in the backbone, either linear or branched. The phrase “Ci-6 alkylene” refers to alkylene chain having from 1 to 6 carbon atoms, both inclusive unless defined otherwise. Suitable non-limiting examples of alkylene groups include, e.g., methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), 1,2-dimethylethylene, and butylene. Unless set forth or recited to the contrary, all alkylene groups described or claimed herein are optionally substituted.

[0036] The term “cycloalkyl” as used herein refers to a non-aromatic mono, multicyclic, bridged multicyclic or spiro-multicyclic ring system. The phrase “C3-6 cycloalkyl” refers to cycloalkyl ring having from 3 to 6 carbon atoms unless specified otherwise. Monocyclic ring includes, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. All cycloalkyl ring described or claimed herein are optionally substituted at any position.

[0037] The term "-Cis alkoxy" denotes an alkyl group having from 1-6 carbon atoms and attached via an oxygen linkage to the rest of the molecule. Representative examples of such groups are -OCH3 and -OC2H5. Unless set forth or recited to the contrary, all alkoxy groups described or claimed herein may be linear or branched, substituted or unsubstituted.

[0038] The term ‘linker ’ is defined as a chemical moiety that connects the payload or active drug molecule to the target specific antibody. A linker may comprise of a self- immolative group, a spacer group and optionally an amino acid or peptide sequence.

[0039] The self-immolative group or the peptide sequence may be optionally substituted, preferable with hydrophilic moieties.

[0040] The term “self-immolative group ” refers to a group that has a tendency undergo a cascade of disassembly reactions ultimately leading to release of the active molecule. Such cascade of disassembly reactions are usually triggered due to enzymatic activation of the amino acid or the peptide (A) next to a self-immolative group (Q). Enzymes such as cathepsins and plasmin are non-limiting examples of enzymes that trigger self- immolation of Q of the present invention.

[0041] The term ‘peptide ’ comprise two or more, same or different amino acids. The amino acids used for the present disclosure can be selected from natural or non-natural amino acids. It can be racemic or a stereoisomer. In a particular embodiment, the amino acids used in the present disclosure are stereoisomers. In another particular embodiment, the amino acids used in the present disclosure are dextro- rotatory or levorotatory.

[0042] The term “ambient temperature ” refers to a temperature ranging from about 15 °C to 35 °C, preferably to a temperature ranging from about 20 °C to 30 °C, more preferably to a temperature of 25 °C.

[0043] The term “optional” or “optionally” refers to the instance, event or circumstance described in the specification which may or may not occur, and that the description includes instances where the event occurs and instances where it does not. The said instance, event or circumstances may be mentioned immediately post the term “optional” or “optionally”, say for example, “optionally substituted” .

[0044] The term “antibody” as used herein, is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired antigen-binding activity. The numbering of the antibody amino acids is according to Kabat EU Index (See Kabat, E. A., el al., Sequences of Protein of immunological interest, Fifth Edition, US Department of Health and Human Services, US Government Printing Office (1991)).

[0045] The term “monoclonal antibody” as used herein, refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally beingpresent in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phagedisplay methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein.

[0046] The term “humanized antibody” as used herein refers to an antibody that is based on the structure of a non -human species (e.g., a mouse) whose amino acid sequence has been modified to increase its similarity to antibody variants produced naturally in humans. Methods for the preparation of humanized are known in the art.

[0047] A "therapeutically effective amount" refers to the amount of a compound that, when administered to a subject in need thereof, is sufficient to cause a desired effect. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity, age, weight, physical condition and responsiveness of the subject to be treated.

[0048] One embodiment of the present disclosure relates to a compound of Formula I:or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-NH-R4, -NR5R6, -O-C1-6 alkyl-O-Ci-6 alkyl-CON(R7)- NH-R8and -CO-NR9R10; whereinR3is selected from hydrogen, and -Ci-6-alkyl;R4is selected from hydrogen, -C1-4 alkyl, -Ci-ealkyl-COOH, -C3-6 cycloalkyl-COOH, - Ci-6 alkyl-CONRnR12, -Ci-6-alkyl-NR13R14, and -C1-6 alkyl-OR15;R5is -Ci-e alkyl-COOH;R6is -Ci-6 alkyl-CONHNH2;R7is selected from hydrogen and -Ci-6-alkyl;R8is selected from hydrogen and -Ci-6-alkyl;R9is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R10is selected from -(CH2)I-6NH-CH2-(CHOH)I-6-CH2OH, -(CH2)I-6NH-CH2- (CHOH)I-6-COOH, -(CH2)I-6NH-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH, and -C1-6- alkyl-COOH;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched C1-6 alkylene which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl and R17is hydrogen or -C1-3 alkyl.

[0049] In one embodiment, in the compound of Formula I:R1is selected from -NH2and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-NH-R4, -NR5R6, -O-C1-6 alkyl-O-Ci-6 alkyl-CON(R7)-NH-R8and -CO-NR9R10; whereinR3is selected from hydrogen and -Ci-3-alkyl;R4is selected from hydrogen, -Ci-3-alkyl, -Ci-6 alkyl-COOH, -Ci-6 alkyl-CONRnR12, - Ci-6-alkyl-NR13R14, and -Ci-6 alkyl-OR15;R5is -C 1-6 alkyl-COOH;R6is -Ci-6 alkyl-CONHNH2;R7is hydrogen;R8is hydrogen;R9is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R10is selected from -(CH2)I-3NH-CH2-(CHOH)I-6-CH2OH, -(CH2)I-3NH-CH2- (CHOH)i-e-COOH, -(CH2)I-3NH-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH, and -C1-3- alkyl-COOH;R11is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-3-alkyl-COOH;R13is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched -C1-6 alkylene which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

[0050] In one embodiment, in the compound of Formula I:R1is -NH2;R2is -CON(R3)-NH-R4, whereinR3is hydrogen;R4is selected from hydrogen, methyl, -C1-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, -Ci- 3-alkyl-NR13R14, and -C1-3 alkyl-OR15;R11is selected from hydrogen, -Ci-2-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)4-CH2OH and -CH2-(CHOH)4-COOH and -CH2- (CHOH)4-CH2O-(CH2)-COOH;R13is -Ci-3-alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH;Y is -(CH2)m, wherein m is 1 ; andZ is Ci-3 alkylene.

[0051] In one embodiment, in the compound of Formula I:R1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is selected from hydrogen, methyl, -C1-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, -Ci- 3-alkyl-NR13R14, and -C1-3 alkyl-OR15;R11is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;R13is -Ci-3-alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH;Y is -CH2-; andZ is C1-4 alkylene.

[0052] In one embodiment, in the compound of Formula I:R1is -NH2;R2is -CO-NR9R10; whereinR9is hydrogen;R10is -(CH2)2-3NH-CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ; andZ is ethylene, which is unsubstituted.

[0053] In one embodiment, in the compound of Formula I:R1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is -CH2COOH;Y is -(CH2)m, wherein m is 1 ; andZ is propylene, which is unsubstituted.

[0054] In one embodiment, in the compound of Formula I:R1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is -(CH2)2COOH;Y is -(CH2)m, wherein m is 1 ; andZ is propylene, which is unsubstituted.

[0055] In one embodiment, in the compound of Formula I:R1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is -(CH2)2-CONRnR12;R11is methyl;R12is -CH2-(CHOH)4-CH2OHY is -(CH2)m, wherein m is 1 ; andZ is propylene, which is unsubstituted.

[0056] One embodiment of the present disclosure relates to a compound of Formula la:Formula-la pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof; wherein:R3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-e alkyl-COOH, -C3-6 cycloalkyl-COOH, - Ci-6 alkyl-CONRnR12, -Ci-6-alkyl-NR13R14, and -C1-6 alkyl-OR15;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched C1-6 alkylene which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

[0057] In one embodiment, in the compound of Formula la:R3is hydrogen;R4is selected from hydrogen, -Ci-4-alkyl, -C1-6 alkyl-COOH, -C1-6 alkyl-CONRnR12- Ci-6-alkyl-NR13R14, and -C1-6 alkyl-OR15;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH and -CH2- (CHOH)4-CH2O-(CH2)-COOH;R13is selected from -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is -CH2-(CHOH)I-6-COOH; andZ is -Ci-6 alkylene, which is unsubstituted.

[0058] In one embodiment, in the compound of Formula la:R3is hydrogen;R4is selected from hydrogen, -Ci-2-alkyl, -C1-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, - Ci-3-alkyl-NR13R14, and -C1-3 alkyl-OR15;R11is selected from hydrogen, -Ci-2-alkyl and -C2-3-alkyl-COOH;R12is selected from -CH2-(CHOH)4-CH2OH, -CH2-(CHOH)4-COOH and -CH2- (CHOH)4-CH2O-(CH2)-COOH;R13is -Ci-3-alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH; andZ is C1-3 alkylene, which is unsubstituted.

[0059] In one embodiment, in the compound of Formula la:R3is hydrogen;R4is selected from hydrogen, -Ci-2-alkyl, -C2-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, - C2-3-alkyl-NR13R14, and -C2-3 alkyl-OR15;R11is selected from hydrogen, methyl and -C2-3 -alkyl-COOH;R12is -CH2-(CHOH)4-CH2OH;R13is -Ci-3-alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH; andZ is C2-3 alkylene, which is unsubstituted.

[0060] In one embodiment, in the compound of Formula la:R3is hydrogen;R4is -C1-3 alkyl-COOH; andZ is propylene, which is unsubstituted.

[0061] One embodiment of the present disclosure relates to a compound of Formula lb,Formula-Ib or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof; wherein p is an integer between 1-6;R3is selected from hydrogen and -Ci-4-alkyl;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

[0062] In one embodiment, in the compound of Formula lb:R11is selected from hydrogen, -Ci-2-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)4-CH2OH, -CH2-(CHOH)4-COOH, -CH2-(CHOH)4- CH2O-(CH2)-COOH and -CH2-(CHOH)4-CH2O-(CH2)-COOH; andZ is C1-3 alkylene, which is unsubstituted.

[0063] In one embodiment, the compound of Formula I is selected from the following:or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof.

[0064] In one embodiment, the compound of Formula I is selected from the following:

[0065] In one embodiment, the compound of Formula I is selected from the following:

[0066] One embodiment of the present disclosure provides a pharmaceutical composition comprising a compound of Formula I, Formula la or Formula lb and pharmaceutically acceptable excipient.

[0067] One embodiment of the present disclosure provides a method of treating disease or disorder mediated by STING in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of Formula I, Formula la or Formula lb or a pharmaceutically acceptable salt thereof.

[0068] One embodiment of the present disclosure provides use of the compound of Formula I, Formula la or Formula lb or a pharmaceutically acceptable salt thereof for the treatment of diseases or disorders mediated by STING.

[0069] One embodiment of the present disclosure provides use of the compound of Formula I, Formula la or Formula lb or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating a disease or disorder mediated by STING.

[0070] In one embodiment, the STING mediated disease or disorder is selected from inflammation, allergic diseases, autoimmune diseases, infectious diseases, cancer, pre- cancerous syndromes, sickle cell disease, sickle cell anaemia, systemic lupus erythematosus (SLE), cutaneous lupus, lupus nephritis, psoriasis, diabetes mellitus including insulin-dependent diabetes mellitus (IDDM), dermatomyositis, systemic sclerosis (scleroderma), and Sjogren's syndrome (SS), rheumatoid arthritis, psoriatic arthritis, STING associated vasculitis with onset at infancy (SAVI), Aicardi Goutieres syndrome (AGS), chilblain lupus, and mixed connective tissue disease.

[0071] In one embodiment, the cancer is selected from myelodysplastic syndrome, melanoma, germ cell tumors, gastrointestinal stromal tumor (GIST), non-small cell lung carcinoma (NSCLC), mastocytosis, neuroblastoma, glioblastoma, astrocytoma,hepatocellular carcinoma, renal cell cancer, breast cancer, cutaneous systemic sclerosis, prostate and colorectal cancer, brain cancer, bladder cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, head and neck cancer, liver cancer, lung cancer, lymphoma, ovarian cancer, pancreatic cancer, renal cancer, skin cancer, stomach cancer, testis cancer, thyroid cancer, and urothelial cancer and other solid tumors.

[0072] One embodiment of the present disclosure provides a construct of Formula C-I or Formula C-II:Formula C-I Formula C-II and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula I with a linker of Formula[-Q-A-L or , whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)-, -NR5R6, -O-C1-4 alkyl-O-Ci-4 alkyl- CON(R7)- N(R8)- and -CO-NR9R10-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, -C3-6-cycloalkyl-COOH, -Ci-6-alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -C1-6 alkyl-COOH;R6is -C1-6 alkyl-CONHNH-;R7' is selected from hydrogen and -C1-6 alkyl;R8is selected from hydrogen and -Ci-6 alkyl;R9' is selected from hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6-COOH)- and -(CH2)I-6N(-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl, and R17' is hydrogen or -C1-3 alkyl;Q is selected from following moieties:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q with L-4 at position #;A is a natural or non-natural amino acid or a peptide of 2 to 5 amino acids, wherein A is attached to Q through its C terminal; andL is selected from following moieties:wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0073] In one embodiment, in the construct of Formula C-I or Formula C-II, A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from following moieties:Moiety A-4 wherein w is an integer selected from 1 to 24.The term Cs or Ce-acid derivatives of pentose and hexose refers to pentose and hexose compounds, wherein the aldehyde or hydroxyl groups are oxidized to carboxylic acid group. For example, the Cs or Ce acid derivative of pentose and hexose is selected from xyluronic acid, glucuronic acid and galacturonic acid etc.

[0074] In one embodiment, in the construct of Formula C-I or Formula C-II, Q is Moiety Q-l and A is peptide selected from Moiety A-2, wherein w is an integer selected from 1 to 24, and Moiety A-4.

[0075] In one embodiment, in the construct of Formula C-I or Formula C-II:Q is Moiety Q-l;A is a peptide selected from Moiety A-2 wherein w is an integer selected from 1 to 24, and Moiety A-4; andL is Moiety L-2, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0076] In one embodiment, in the construct of Formula C-I and C-II:R1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CONR9R10;R3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, -Ci-6-alkyl-CONR11R12';R9is hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6-COOH)- and -(CH2)I-6N(-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl; and R17is hydrogen or -C1-3 alkyl;Q is selected from Moiety Q-l, Moiety Q-2 and Moiety Q-3; wherein ‘]’ denotes attachment of Q to R2; and ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q to L-4 at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala- Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly- Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val, which is unsubstituted or substituted with -C1-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective C5 or Ce-acid derivatives,ORA is a peptide selected from Moiety A-l, Moiety A-2 wherein w is an integer selected from 1 to 24, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6; wherein A is attached to Q through its C terminal; andL is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0077] In one embodiment, in the construct of Formula C-I or Formula C-II:R1is -NH2;R2is -CON(R3)-NH-R4, whereinR3’ is hydrogen;R4' is selected from hydrogen, -Ci-3-alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl- CONRnR12;Rn' is hydrogen, -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -CH2-;Z is straight C1-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l, Moiety Q-2 and Moiety Q-3, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q to L at position #;A is a peptide selected from Moiety A-l, Moiety A-2 wherein w is an integer selected from 1 to 24, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6; wherein A is attached to Q through its C terminal; andL is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4, wherein s is an integer selected from 1-4 and t is an integer selected from 4-18.

[0078] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is selected from -CON(R3)-NR4- and -CO-NR9R10-; whereinR3is hydrogen;R4is selected from hydrogen, -C1-3 alkyl-COOH and -C1-3 alkyl-CONRnR12';R9is hydrogen;R10' is-(CH2)i-6N(-CH2-(CHOH)i-6-CH2OH)-;R11is selected from hydrogen and -Ci-6-alkyl;R12is -CH2-(CHOH)I-6-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is C1-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l, Moiety Q-2 and Moiety Q-3, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q to L at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala- Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly- Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from Moiety A-l, Moiety A-2 wherein w is an integer selected from 1 to 24, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6; wherein A is attached to Q through its C terminal; andL is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0079] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is selected from -CON(R3)-NR4- and -CO-NR9R10-; whereinR3is hydrogen;R4is selected from hydrogen, -Ci-ealkyl-COOH and -Ci-6 alkyl-CONRnR12';R9is hydrogen;R10' is-(CH2)i-6N(-CH2-(CHOH)i-6-CH2OH)-;R11is selected from hydrogen and -Ci-3-alkyl;R12is -CH2-(CHOH)I-4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is Ci-3 alkylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is peptide selected from Moiety A-2 wherein w is an integer selected from 4 to 18 and Moiety A-4; andL is Moiety L-2, wherein s is an integer selected from 1-3 and t is an integer selected from 4-18.

[0080] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0081] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4' is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

[0082] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0083] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

[0084] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

[0085] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-, whereinR3is hydrogen;R4is -(CH2)2-CONRnR12'; whereinR1 ris methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0086] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-CONRnR12;R1 ris methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

[0087] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

[0088] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0089] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CONR9R10-; whereinR9is hydrogen;R10' is -(CH2)2N(-CH2-(CHOH)4-CH2OH)-;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

[0090] One embodiment of the present disclosure provides a construct of Formula C- la:Formula C-Ia and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula la with a linker of Formula [-Q-A-L, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH, -C3-6 cycloalkyl-COOH, -C1-6 alkyl-CONR11R12, -Ci-6-alkyl-NR1,3R’14’, and -C1-6 alkyl-OR15’;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl;Q is selected from following moieties:an whereindenotes attachment of Q to A;A is a natural or non-natural amino acid or a peptide of 2 to 5 amino acids, wherein A is attached to Q through its C terminal; andL is selected from following moietieswherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0091] In one embodiment, in the construct of Formula C-Ia:R3is hydrogen;R4is selected from hydrogen, -Ci-6 alkyl-COOH and -Ci-6 alkyl-CONR11R12;R11is selected from hydrogen and -Ci-6-alkyl;R12is -CH2-(CHOH)I-6-CH2OH; and Z is Ci-6 alkylene, which is unsubstituted;Q is Moiety Q-l, wherein ‘}’ denotes attachment of Q to A;A is a peptide selected from following moieties:wherein w is an integer selected from 1 to 24, andL is Moiety L-2, wherein s is an integer selected from 2-4 and t is an integer selected from 2-4.

[0092] In one embodiment, in the construct of Formula C-Ia:R3is hydrogen;R4is selected from hydrogen, methyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONR11R12;R11is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH; and Z is Ci-6 alkylene, which is unsubstituted.

[0093] In one embodiment, in the construct of Formula C-Ia, Q is Moiety Q-l.

[0094] In one embodiment, in the construct of Formula C-Ia, Q is Moiety Q-l and A is peptide selected from Moiety A-2, wherein w is an integer selected from 1 to 24, and Moiety A-4.

[0095] In one embodiment, in the construct of Formula C-Ia:Q is Moiety Q-l;A is peptide selected from Moiety A-2, wherein w is an integer selected from 1 to 24, and Moiety A-4; andL is Moiety L-2, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0096] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4' is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0097] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

[0098] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0099] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

[0100] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

[0101] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-CONRnR12;R1 ris methyl;R12is CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0102] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-CONRnR12;R1 ris methyl;R12is CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

[0103] In one embodiment, in the construct of Formula C-I:R1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

[0104] In one embodiment, in the construct of Formula C-LR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CFbjm, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

[0105] One embodiment of the present disclosure provides an antibody -drug conjugate of Formula A:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula I to an antibody via a linker U, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)-, -NR5R6-, -O-C1-4 alkyl-O-Ci-4 alkyl- CON(R7)-N(R8)- and -CO-NR9R10-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, -G-6-cycloalkyl-COOH. -Ci-6-alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -C1-6 alkyl-COOH;R6is -C1-6 alkyl-CONHNH-;R7' is selected from hydrogen and -C1-6 alkyl;R8is selected from hydrogen and -C1-6 alkyl;R9is selected from hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6-COOH)- and -(CH2)I-6N(CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH ;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

[0106] In one embodiment, in the antibody -drug conjugate of Formula A:R1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CONR9R10;R3is selected from hydrogen and -Ci-6-alkyl;R4' is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH and -Ci-6-alkyl- CONRnR12;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CFbjm, wherein m is 1 to 4;Z is straight or branched C1-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

[0107] In one embodiment, in the antibody -drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-NR4-;R3is hydrogen;R4' is selected from hydrogen, -C1-3 alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl- CONRnR12;R11is selected from hydrogen and -Ci-3-alkyl;R12is selected from -CH2-(CHOH)4-CH2OH and -CH2-(CHOH)4-COOH;Y is -CH2-;Z is straight C1-6 alkylene, which is unsubstituted;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

[0108] In one embodiment, in the antibody drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-NR4-;R3is hydrogen;R4’ is selected from hydrogen, methyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONRnR12';R11is selected from hydrogen and -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -CH2-;Z is C1-6 alkylene, which is unsubstituted;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

[0109] In one embodiment, in the antibody drug conjugate of Formula A:R1is -NH2;R2is selected from -CON(R3)-NR4- and -CO-NR9R10; whereinR3is hydrogen;R4is selected from hydrogen, -C1-3 alkyl-COOH and -C1-3 alkyl-CONRnR12';R9is hydrogen;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-;R11is hydrogen;R12is -CH2-(CHOH)I-4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is straight or branched C1-6 alkylene, which is unsubstituted;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

[0110] In one embodiment, in the antibody-drug conjugate of Formula A, the compound of Formula I is selected from the following:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, wherein ‘*’ represents point of attachment to U.

[0111] In one embodiment, in the antibody-drug conjugate of Formula A, U is linker moiety with following structure:AI[-Q-A-L1- or, wherein Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L', while ‘)’ denotes the attachment of Q to L' at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala- Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly- Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from following moieties:wherein w is an integer selected from 1-24 and A is atached to Q through its C terminal;L' is a moiety selected from:Moiety L'-4 wherein ‘**’ is atachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24.

[0112] In one embodiment, in the antibody-drug conjugate of Formula A, the Ab is an antibody binding to MUC1, EGFR, HER2, HER3, MUC16, TROP2, Nectin-4, 5T4, PSMA, CD19, CD22, CD33, CD37, CD38, CD40, CD44, CD52, CD79b, GPR20, FAP, cMET or GRP78.

[0113] In one embodiment, in the antibody-drug conjugate of Formula A, the Ab is an antibody binding to MUC1-SEA domain or HER2.

[0114] In one embodiment, antibody is a humanized antibody binding to SEA-a-[3 region ofMUCl. PCT / IB2024 / 057438 discloses examples of different variants ofHMl LM2, HM2 LM1, HM2 LM2, HM3 LM2, HM4 LM2, HM4 LM3 and HM5 LM2, HM5 LM3 and HM5 LM4 of humanized anti-MUCl antibody specifically directed against the junction of the alpha and beta chains (which comprises the SEA domain) of MUC 1.

[0115] In one embodiment, in the antibody-drug conjugate of Formula A, the antibody is humanized monoclonal antibody which binds to the MUC 1 -SEA domain comprisesa heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0116] In one embodiment, in the antibody -drug conjugate of Formula A:R1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CONR9R10;R3is selected from hydrogen and -Ci-6-alkyl;R4' is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH and -Ci-6-alkyl- CONRnR12;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CFEjm, wherein m is 1 to 4;Z is straight or branched C1-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen and -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;U is a linker moiety connecting compound of Formula I to the antibody; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0117] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4' is hydrogen;Y is -(CFEjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1- , whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0118] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is hydrogen;Y is -(CFEjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0119] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0120] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CFEjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0121] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CFEjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0122] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0123] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONR11R12;R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0124] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3' is hydrogen;R4is -CH2CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0125] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3' is hydrogen;R4is -CH2CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0126] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CO-NR9R10-, whereinR9' is hydrogen;R10' is -(CH2)2N(-CH2-(CHOH)4-CH2OH)-;Y is -(CFEjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0127] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0128] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is trastuzumab.

[0129] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0130] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CFbjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0131] In one embodiment, in the antibody-drug conjugate of Formula A:R1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONR11R12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0132] One embodiment of the present disclosure provides an antibody -drug conjugate of Formula A-I or Formula A-II:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the construct of Formula C-I or Formula C-II, respectively with a linker of Formula[-Q-A-L’ or , whereinR1is -NH2 and -NH-Ci-6-alkyl;R2is -CON(R3)-N(R4)-, -NR5R6-, -O-Ci-4 alkyl-O-Ci-4 alkyl-CON(R7')-N(R8')- and - CO-NR9R10'-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, -C3-6-cycloalkyl-COOH, -Ci-6-alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -C1-6 alkyl-COOH;R6is -C1-6 alkyl-CONHNH-;R7' is selected from hydrogen and -C1-6 alkyl;R8' is selected from hydrogen and -C1-6 alkyl;R9' is selected from hydrogen, -C1-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6-N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6-N(-CH2-(CHOH)I-6- COOH)-, and -(CH2)I-6-N(CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH,-CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4;Z is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16'R17', wherein R16' is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl;Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L', while ‘)’ denotes the attachment of Q to L' at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala- Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly- Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from following moieties:Moiety A-4 wherein w is an integer selected from 1-24 and A is attached to Q through its C terminal;L' is a moiety selected from:Moiety L’-4 wherein ‘**’ is atachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24; andAb is an antibody.

[0133] In one embodiment, in the antibody-drug conjugate of Formula A-I:R1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CON(R9R10)R3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH and -Ci-6-alkyl- CONRnR12;R9is selected from hydrogen, -C1-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6-N(-CH2-(CHOH)I-6-CH2OH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CFbjm, wherein m is 1 to 4;Z is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17wherein R16is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Q is selected from Moiety Q-l and Moiety Q-2, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is a peptide selected from Moiety A- 1, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 and A is attached to Q through its C terminal;L1is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4; wherein s is an integer selected from 2-4 and t is an integer selected from 4-18; andAb is an antibody.

[0134] In one embodiment, in the antibody -drug conjugate of Formula A-I:R1is -NH2;R2is -CON(R3)-NR4-, whereinR3is hydrogen;R4' is selected from hydrogen, -Ci-3-alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl- CONRnR12;R11is selected from hydrogen and -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -(CFbjm, wherein m is 1 ;Z is straight or branched C1-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is a peptide selected from Moiety A- 1, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 and A is attached to Q through its C terminal;L1is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is an antibody.

[0135] In one embodiment, in the antibody-drug conjugate of Formula A-I:R1is -NH2;R2is -CON(R3)-NR4-, whereinR3is hydrogen;R4' is selected from hydrogen, -Ci-3-alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl- CONRnR12;R11is selected from hydrogen and -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -(CH2)m, wherein m is 1 ;Z is straight or branched C1-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is a peptide selected from Moiety A- 1, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 w and A is attached to Q through its C terminal;L1is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is a humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0136] One embodiment ofthe present disclosure provides an antibody-drug conjugate of Formula A-Ia:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the construct of Formula C-Ia, wherein R3is selected from hydrogen and -Ci-4-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-ealkyl-COOH, -C3-6 cycloalkyl-COOH, -Ci- 6 alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -C1-6 alkyl-OR15';Rnis selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -(CH2)I-6NH- CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14' is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Z is straight or branched C1-6 alkylene, which is unsubstituted or substituted with hydroxy, -C1-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L', while ‘)’ denotes the attachment of Q to L' at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val- Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly-Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce-acid derivatives,ORA is a peptide selected from following moieties:wherein w is an integer selected from 1-24 and A is atached to Q through its C terminal; andL' is selected fromMoiety L'-4 wherein ‘**’ is atachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24; andAb is an antibody.

[0137] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is selected from hydrogen and -Ci-4-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH and -Ci-6alkyl-CONR11R12';Rn' is selected from hydrogen and -Ci-6-alkyl;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Z is Ci-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2; wherein ‘]’ denotes atachment of Q to R2; while ‘}’ denotes attachment of Q to A or L';A is a peptide selected from Moiety A-l, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A- 5 and Moiety A-6, wherein w is an integer between 4-18 w and A is attached to Q through its C terminal; andL' is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is an antibody.

[0138] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is selected from hydrogen and -Ci-4-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH and -Ci-6alkyl-CONR11R12';Rn' is selected from hydrogen and -Ci-6-alkyl;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Z is Ci-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L';A is a peptide selected from Moiety A-l, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A- 5 and Moiety A-6, wherein w is an integer between 4-18 w and A is attached to Q through its C terminal; andL' is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0139] In one embodiment, in the antibody-drug conjugate of Formula A-Ia, Q is Moiety Q-l.

[0140] In one embodiment, in the antibody-drug conjugate of Formula A-Ia, Q is Moiety Q-l and A is peptide selected from Moiety A-2, wherein w is an integer between 1-24 and Moiety A-4.

[0141] In one embodiment, in the antibody-drug conjugate of Formula A-Ia, Q is Moiety Q-l; A is peptide selected from Moiety A-2 and Moiety A-4 and L’ is Moiety L’-2.

[0142] In one embodiment, in the antibody-drug conjugate of Formula A-Ia, the Ab is an antibody binding to MUC1, EGFR, HER2, HER3, MUC16, TROP2, Nectin-4, 5T4, PSMA, CD19, CD22, CD33, CD37, CD38, CD40, CD44, CD52, CD79b, GPR20 , FAP, cMET or GRP78.

[0143] In one embodiment, in the antibody-drug conjugate of Formula A-Ia, the Ab is an antibody binding to MUC1-SEA domain or HER2.

[0144] In one embodiment, in the antibody -drug conjugate of Formula A-Ia, the antibody is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0145] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is hydrogen;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0146] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4' is hydrogen;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0147] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0148] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0149] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0150] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8; andL’ is Moiety L’-2, wherein s is integer 2 and t is integer 4;Ab is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0151] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0152] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3' is hydrogen;R4is -CH2CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0153] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -CH2CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0154] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4' is hydrogen;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0155] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is trastuzumab.

[0156] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0157] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0158] In one embodiment, in the antibody-drug conjugate of Formula A-Ia:R3is hydrogen;R4is -Ci-6-alkyl-CONR11R12';R11is methyl;R12is CH2-(CHOH)4-CH2OH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

[0159] One embodiment of the present disclosure provides a pharmaceutical composition comprising an antibody-drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia and pharmaceutically acceptable excipient.

[0160] One embodiment of the present disclosure provides a method of treating disease or disorder mediated by STING in a subject comprising administering to the subject a therapeutically effective amount of the antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia and pharmaceutically acceptable excipient.

[0161] One embodiment of the present disclosure provides use of an antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a disease or disorder mediated by STING.

[0162] One embodiment of the present disclosure provides use of an antibody drug conjugate of Formula-A, Formula A-I, Formula A-II or Formula A-Ia or a pharmaceutically acceptable salt thereof, for treating a disease or disorder mediated by STING.

[0163] In one embodiment, the disease or disorder mediated by STING is selected from inflammation, allergic diseases, autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes, sickle cell disease, sickle cell anaemia, systemic lupus erythematosus (SLE), cutaneous lupus, lupus nephritis, psoriasis, diabetes mellitus including insulin-dependent diabetes mellitus (IDDM), dermatomyositis, systemic sclerosis (scleroderma), and Sjogren's syndrome (SS), rheumatoid arthritis, psoriatic arthritis, STING associated vasculitis with onset at infancy (SAVI), Aicardi Goutieres syndrome (AGS), chilblain lupus, and mixed connective tissue disease.

[0164] In one embodiment, the disease or disorder mediated by STING is cancer selected from myelodysplastic syndrome, melanoma, germ cell tumors, gastrointestinal stromal tumor (GIST), non-small cell lung carcinoma (NSCLC), mastocytosis, neuroblastoma, glioblastoma, astrocytoma, hepatocellular carcinoma, renal cell cancer, breast cancer, cutaneous systemic sclerosis, prostate and colorectal cancer, brain cancer, bladder cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, head and neck cancer, liver cancer, lung cancer, lymphoma, ovarian cancer, pancreatic cancer, renal cancer, skin cancer, stomach cancer, testis cancer, thyroid cancer, and urothelial cancer and other solid tumors.

[0165] In one embodiment, the present disclosure also provides a method for treatment of disorders mediated by STING, comprising administering to a mammal in need of such treatment an effective amount of compounds of the present disclosure or a pharmaceutically acceptable salts, stereoisomer and / or deuterated analogs thereof.

[0166] One embodiment of the present disclosure provides a compound selected from:or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof.

[0167] In another aspect, the present disclosure provides a compound or a pharmaceutically acceptable salt, stereoisomer or deutereted analog thereof, selected from the representative compounds as shown in Table 1 below:

[0168] Table 1: Embodiment of present invention: STING agonist compound of Formula I, Formula la and Formula lb according to present disclosure

[0169] In another aspect, the present disclosure provides a construct or a pharmaceutically acceptable salt, stereoisomer or deutereted analog thereof, selected from the representative compounds as shown in Table 2 below:

[0170] Table 2: Embodiment of present invention: Constructs of Formula C-I,Formula C-II, Formula C-Ia and Formula C-Ibconjugates of Formula A-I, Formula A-II and Formula A-Ia, formed by the conjugation of Construct of Formula C-I, Formula C-II, Formula C-Ia and Formula C-Ib, wherein the antibody is a humanized form of any one of chimeric antibodies DMB4F4 (4F4), DMB7F3 (7F3), or DMB10F10 (10F10), each of which is described in International Publication No. WO 2021 / 186427, which is hereby incorporated in below table 3.

[0172] Table 3: Embodiment of present invention: ADC of Formula A, Formula A-I, Formula A-II and Formula A-Ia according to present disclosurewherein d is DAR between 1-10 and HM5LM4 is a humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0173] In another embodiment, the present disclosure provides deuterated analogs of compounds of the present disclosure, wherein one or more hydrogen atoms are replaced with deuterium. Such compounds can be synthesized by means well known in the art, for example by employing starting materials in which one or more hydrogen atoms have been replaced with deuterium. Deuterated analogs may have improved drug metabolism and pharmacokinetics properties, See, for example, Foster, “Deuterium Isotope Effects in Studies of Drug Metabolism,” Trends Pharmacol. Sci., 5(12):524- 527 (1984).

[0174] Pharmaceutical Compositions:

[0175] Any of the compounds disclosed herein may be formulated into a composition that additionally comprises one or more suitable pharmaceutically acceptable carriers,including excipients and other compounds that facilitate administration of the compound to a subject. The pharmaceutical compositions may be formulated in a conventional manner using one or more pharmaceutically acceptable excipients.

[0176] Such pharmaceutical compositions and the processes for preparing the same are described, for example, in Remington: The Science and Practice of Pharmacy (D. B. Troy, Editor, 21stEdition, Lippincott, Williams & Wilkins, 2006), the contents of which are incorporated herein by reference in their entirety.

[0177] Thus, in one embodiment, the present disclosure provides a pharmaceutical composition comprising a compound according to the present disclosure, or a pharmaceutically acceptable salt or deuterated analog thereof, and a pharmaceutically acceptable carrier, diluent, or excipient.

[0178] Suitable pharmaceutically acceptable doses of the compounds for use in treating any of the diseases, disorders and / or conditions described herein can be determined by those skilled in the relevant art. Therapeutic doses are generally identified through a dose ranging study in humans based on preliminary evidence derived from animal studies.

[0179] General Synthetic Methods for the Preparation of Compounds

[0180] Compounds of Formula I can be prepared as depicted in General Scheme 1 by reacting the key general intermediate GI-14 (wherein R1is as defined in the specification) with appropriately substituted pyrazole-5 -carboxylic acids (wherein Z and R2are as defined in the specification) using amide coupling condition.General scheme 1

[0181] Compounds of Formula la can be prepared as depicted in General Scheme 2 by initially reacting the key general intermediate GI-14 with appropriately substituted andprotected form of pyrazole-5 -carboxylic acids using amide coupling condition followed by deprotection reaction to obtain another acid intermediates of Formula I'-a (wherein Z and R1are as defined in the specification), which on further reaction with appropriately substituted hydrazine derivatives under amide coupling condition followed by deprotection of protecting groups to furnish the final compounds.General scheme 2

[0182] Compounds of Formula lb can be prepared as depicted in General Scheme 3 by initially reacting compounds of Formula-I'b, wherein Z and R2are as defined in the specification and R is a carboxylic acid functional group, with appropriately substituted general amine intermediate (Rn-NH-R12) using amide coupling condition followed by deprotection reaction as needed to obtain the final compounds.General scheme 3

[0183] Compounds of Formula Ic can be prepared as depicted in General Scheme 4 by initially reacting compounds of Formula-I'-a (wherein Z and R1are as defined in the specification) with appropriately substituted general amine intermediate (R9-NH-R10) using amide coupling condition followed by deprotection reaction as needed to obtain the final compounds.General scheme 4

[0184] SYNTHESIS OF INTERMEDIATES

[0185] Intermediate 14: (3E)-25-Amino-7-(l-ethyl-3-methyl-lH-pyrazole-5- amido)-14,18-dioxa-l,6,8,24-tetraazapentacyclo[17.6.1.16’9.023’26.013’27]heptacosa- 3,7,9,ll,13(27),19,21,23(26),24-nonaene-ll,21-dicarboxamide

[0186] The said intermediate 14 was prepared following a literature method (WO2020132582A1) and the steps have been depicted in Scheme-1. 'H NMR (400 MHz, DMSO-de) 5: 1.33 (t, J=7.00Hz, 3H), 2.18 (s, 3H), 2.20-2.35 (m, 2H), 4.30-4.45 (m, 4H), 4.60-4.75 (m, 4H), 4.85-4.95 (s, 2H), 5.25-5.38 (s, 2H), 6.49 (s, 1H), 6.40- 6.55 (s, 1H), 7.1-7.25 (bs, 2H), 7.30-7.35 (s, 1H), 7.36-7.45 (m, 1H), 7.45-7.55 (s, 1H), 7.80-7.85 (s, 1H), 7.85-7.95 (bs, 2H). LCMS (ESI, m / z): 613.24 [M+H]+.Scheme 1

[0187] Intermediate 15: l-(3-{N'-[( / e / 7- butoxy)carbonyl]hydrazinecarbonyl}propyl)-3-methyl-lH-pyrazole-5-carboxylic acid

[0188] Step-1: To a stirred solution of benzyl 3-methyl-lH-pyrazole-5-carboxylate (5 g; 0.2 mol), was added tert-butyl 4-bromobutanoate (6.2 g, 0.027 mol) and potassium carbonate (6.4 g, 0.21 mol) in DMF (50 mb). The reaction mixture was stirred at 90-95 °C for 8 hr, fdtered and concentrated under reduced pressure. The crude product was mixed with water (25 mL) and extracted with ethyl acetate (3x50 mb). The organic layer was washed with water (50 mL), brine solution (50 mL) and dried over sodium sulphate. The organic layer was concentrated under reduced pressure and the residue was purified by silica gel column chromatography using mobile phase Hexane: Ethyl Acetate (85: 15) to yield desired product, benzyl l-[4-(tert-butoxy)-4-oxobutyl]-3- methyl-lH-pyrazole-5-carboxylate. LCMS (ESI, m / z): 381.20 [M+Na]+, 303.2 [loss of tert-butyl fragment] .

[0189] Step-2: To a stirred solution of benzyl l-[4-(tert-butoxy)-4-oxobutyl]-3- methyl-lH-pyrazole-5-carboxylate (5 g, 0.014 mol) in DCM (50 mL), was added TFA (25 mL) at 0-5 °C and the reaction mixture was stirred at RT for 20 hr. The reaction mixture was worked up with saturated bicarbonate solution (25 mL), extracted with DCM (3x50 mL) and the organic layer was washed with water (50 mL), brine solution (50 mL) and dried over sodium sulphate. The organic layers were concentrated under reduced pressure to get the corresponding acid. LCMS (ESI, m / z): 303.2 [M+H]+.

[0190] Step-3: To a stirred solution of 4-{5-[(benzyloxy)carbonyl]-3-methyl-lH- pyrazol-l-yl}butanoic acid (1.5 g, 0.005 mol), HATU (2.79 g, 0.0073 mol), DIPEA (2.63 mL, 0.014 mol) in DMF (15 mL) was added tert-butylcarbazate (0.77 g, 0.006 mol) at 0-5 °C. The reaction mixture was stirred at RT for 20 hr. The reaction mixture was concentrated under reduced pressure and quenched with water (10 mL) and extracted with ethyl acetate (3x20 mL). The organic layers were washed with water (10 mL), brine solution (10 mL) and dried over sodium sulphate. The organic layers were concentrated under reduced pressure and the crude product was purified by silica gelcolumn chromatography using mobile phase ethyl acetate to obtain pure product.LCMS (ESI, m / z): 417.4 [M+H]+.

[0191] Step-4: To a stirred solution of benzyl 1 -(3- {N'-[(tert- butoxy)carbonyl]hydrazinecarbonyl}propyl)-3-methyl-lH-pyrazole-5-carboxylate (2 g, 0.005 mol) in methanol (20 mL) was added 10% Pd / C (0.5 g, 20% w / w) and the reaction mixture was stirred under hydrogen atmosphere (balloon pressure) at RT for 20 hr. The reaction mixture was filtered through hyflo and the bed was washed with methanol (3x20 mL). The combined organic layers were concentrated under reduced pressure to obtain the intermediate-15.1HNMR (400 MHz, DMSO-de) 5: 1.38 (s, 9H), 1.91-1.94 (m, 2H), 2.04 (t, J=1 A Hz, 2H), 2.17 (s, 3H), 4.11 (bs, 2H), 4.41 (t, .7=6,8 Hz, 2H), 6.58 (s, 1H), 9.51 (s, 1H). LCMS (ESI, m / z): 325.1 [M-H]’.

[0192] Intermediate-16: l-(3-{N'-[(ter / -Butoxy)carbonyl]-N'-methylhydrazine carbonyl}propyl)-3-methyl-lH-pyrazole-5-carboxylic acid

[0193] Step-1: To a stirred solution of 4-{5-[(benzyloxy)carbonyl]-3-methyl-lH- pyrazol-l-yl}butanoic acid (1.0 g, 0.0033 mol) in DML (20 mL), was added HATU (1.8 g, 0.005 mol) and DIPEA (1.7 mL, 0.0099 mol) at RT under nitrogen atmosphere. The reaction mixture was cooled to 0-5 °C and was added N-methyl-(tert- butoxy)carbohydrazide (0.58 g, 0.0039 mol) and stirred the reaction mixture at RT for 20 hr. The TLC analysis shows the completion of the reaction and the reaction mixture was concentrated under reduced pressure. The crude intermediate was purified by column chromatography using mobile phase Hexane: Ethyl Acetate (30: 70) to obtain benzyl l-(3-{N'-[(tert-Butoxy)carbonyl]-N'-methylhydrazine carbonyl [propyl) -3- methyl-lH-pyrazole-5-carboxylate.1H NMR (400 MHz, DMSO-de) 5: 1.33-1.41 (m, 9H), 1.97-2.04 (m, 4H), 2.2 (s, 3H), 2.94 (m, 3H), 4.43 (t, .7=6,9 Hz, 2H), 5.32 (s, 2H), 7.35-7.47 (m, 5H). LCMS (ESI, m / z): 453.2 [M+Na]+.

[0194] Step-2: To a stirred solution of the product of Step-1 (0.85 g, 0.0019 mol) in methanol (20 mL), was added (0.1 g, 10% Pd / C) and then stirred the reaction mixture under hydrogen atmosphere (balloon pressure) at RT for 4 hr. The TLC analysis shows the completion of the reaction and the reaction mixture was filtered through hyflo bed and washed with methanol (2 x 10 mL). The combined organic layers were concentrated under reduced pressure to get intermediate - 16.JH NMR (400 MHz, DMSO-de) 5: 1.38-1.45 (m, 9H), 2.01 (m, 2H), 2.06-2.08 (m, 2H), 2.22 (s, 3H), 2.36- 2.39 (m, 1H), 2.99 (d, J=25.5 Hz, 3H), 4.46-4.49 (t, .1=6.66 Hz, 2H), 6.65 (s, 1H), 10.06 (bs, 1H). LCMS (ESI, m / z): 363.3 [M+Na]+.

[0195] Intermediate-17: 2- [2- [2- [2-(2-ter / -Butoxycarbonylhydrazino)-2-oxo- ethoxy]ethoxy]ethyl]-5-methyl-pyrazole-3-carboxylic acid

[0196] Step-1: To a cooled solution of methyl 3-methyl-lH-pyrazole-5-carboxylate (2 g, 0.014M), tert-Butyl-2-[2-(2-hydroxyethoxy)ethoxy]acetate (4.7 g, 0.02 IM; prepared as per J. Med. Chem. 2018, 61, 2, 583-598) and triphenylphosphine (5.62 g, 0.021M) in THF (30 mL), was added DIAD (4.15 mL, 0.021 M) slowly dropwise. The reaction mixture was then stirred overnight at room temp. The reaction mixture was concentrated under vacuum to get crude material into which di -isopropyl ether (40 mL) was added and stirred for 15 min, the mixture was fdtered and filtrate was adsorbed over silica gel, column chromatography was performed in ethyl acetate: hexanes. Pure fractions were collected and concentrated under vacuum resulting in methyl l-(2-{2- [2-(tert-Butoxy)-2-oxoethoxy]ethoxy}ethyl)-3-methyl-lH-pyrazole-5-carboxylate. 'H NMR (400 MHz, DMSO-de) 5: 1.46 (s, 9H), 2.26 (s, 3H), 3.6 (m, 2H), 3.64 (m, 2H), 3.85 (s, 3H), 3.95 (s, 2H), 4.69 (t, J=5.94 Hz, 2H), 5.01-4.92 (m, 2H), 6.58 (s, 1H).

[0197] Step-2: To a stirred solution of the product of Step-1 (3 g, 0.0087 M) in DCM (30 mL), was added TFA (15 mL) dropwise at 0 °C. The reaction mixture was then stirred at RT for 4hr. After completion reaction mixture was concentrated under vacuum and co-distilled with toluene (50 mL x 2) and then degassed under vacuum for Ihr. The product obtained was used in next step. LCMS (ESI, m / z): 287.08 [M+H]+.

[0198] Step-3: To a stirred solution ofthe product of Step-2 (3 g, 0.01 M) in DMF (30 mL), was added HATU (6 g, 0.015 M) and DIPEA (9 mL, 0.052 M) at 0 °C, followed by addition of tert-butyl carbazate (1.65 g, 0.012 M). The reaction mixture was allowed to stir at room temp for 3 hr. The reaction mixture was concentrated under vacuum and the resulting crude obtained was purified by column chromatography eluting with ethyl acetate: methanol (0-5%). Pure fractions were collected and concentrated under vacuum to get methyl 2-[2-[2-[2-(2-tert-butoxycarbonylhydrazino)-2-oxo- ethoxy]ethoxy]ethyl]-5-methyl-pyrazole-3-carboxylate.1H NMR (400 MHz, DMSO- d6) 5: 1.46 (s, 9H), 2.26 (s, 3H), 3.58 (m, 2H), 3.64 (m, 2H), 3.82-3.84 (m, 2H), 3.85 (s, 3H), 4.07 (m, 2H), 4.67-4.7 (m, 2H), 6.59 (s, 2H), 8.67 (s, 1H).

[0199] Step-4: To a stirred solution of the product of Step-3 (0.5 g) in methanol (10 mL), was added sodium hydroxide (75 mg) and water (1 mL). The reaction mixture was stirred for 4 hr at room temp. The reaction mixture was acidifed by amberlyst resin and filtered. Filtrate was dried over anhydrous sodium sulphate and then concentrated under vacuum resulting in intermediate - 17. 'HNMR (400 MHz, DMSO-de) d 1.5 (s, 9H), 2.28 (2, 3H), 3.45 (m, 2H), 3.54 (m, 2H), 3.79 (t, .7=4.67 Hz, 2H), 4.08 (s, 2H), 4.8 (t, .7=4,6 Hz, 2H), 6.65 (s, 1H), 6.75 (s, 1H), 9.08 (s, 1H).

[0200] Intermediate-18: 2-[4-[2-ter / -Butoxycarbonyl-2-(2-tert-butoxy-2-oxo- ethyl) hydrazino]-4-oxo-butyl]-5-methyl-pyrazole-3-carboxylicacid

[0201] Step-1: To a solution of 4-(5 -benzyloxy carbonyl-3 -methyl -pyrazol-1- yl)butanoic acid (0.671 g, 2.22 mmol) in DMF (2 mL), under nitrogen atmosphere, was added HATU (1.01 g, 2.66 mmol) and DIPEA (0.46 g, 2.66 mmol) at rt. After stirring for 15 min., tert-butyl 2-[amino(tert-butoxycarbonyl)amino]acetate (0.65 g, 2.66 mmol) was added and continued stirring at RT for 3 hr. The reaction mixture was quenched with aqueous sodium bicarbonate solution and extracted using ethyl acetate(3 x 20 mb). Combine extract was washed with brine, dried over sodium sulphate. Removal of solvent gave crude brown liquid. Pure product was obtained using column chromatography using ethyl acetate: n- hexane solvent as eluent. This resulted into benzyl l-(3-{N'-[2-(tert-Butoxy)-2-oxoethyl]-N'-[(tert-butoxy) carbonyl] hydrazinecarbonyl}propyl)-3-methyl-lH-pyrazole-5-carboxylate. 'H NMR (400 MHz, DMSO-de) 5: 1.44 & 1.45 (s, 9H), 1.46 & 1.48 (s, 9H), 2.08-2.14 (m, 2H), 2.27- 2.29 (m, 2H), 4.62-4.67 (m, 2H), 5.29 & 5.20 (s, 2H), 6.65 & 6.67 (s, 1H), 7.37-7.41 (m, 5H). LCMS (ESI, m / z): 531.30 [M+H]+.

[0202] Step-2: To a stirred solution of the product of Step-1 (0.835 g, 1.57 mmol) in methanol (15 mb), was added 0.2 g, 10 %palladium on carbon (50% wet). The reaction mixture was stirred at RT under hydrogen atmosphere for 3 hr. The solid was fdtered over hyflo bed. The fdtrate was concentrated under vacuum. This resulted into intermediate - 18. 'H NMR (400 MHz, DMSO-de) 5: 1.40 & 1.43 (s, 9H), 1.47 & 1.48 (s, 9H), 1.97-2.01 (m, 2H), 2.09-2.11 (m, 2H), 2.20-2.22 (m, 3H), 3.99 - 4.02 (m, 2H), 4.44 . 4.47 (m, 2H), 6.64 (s, 1H), 10.18 & 10.21 (s, 1H), 13.30 (brs, 1H). LCMS (ESI, m / z): 441.23 [M+H]+.

[0203] Intermediate-19: 2-(4-te / 7-Butoxy-4-oxo-butyl)-5-methyl-pyrazole-3- carboxylic acid

[0204] Step-1: To a stirred solution of benzyl 2-(4-tert-butoxy-4-oxo-buty 1 )-5 -methyl - pyrazole-3 -carboxylate (1.0 g, 0.0027 mol) in methanol (10 mb), was added 10%-Pd / C (0.3 g) and the reaction mixture was stirred under balloon hydrogen pressure at 25 °C for 3 hr. Completion of reaction was monitored by TLC analysis. The reaction mixture was fdtered through celite hyflo bed and washed with methanol (2 x 20 mb). The organics were concentrated under reduced pressure to get intermediate -19.JH NMR (400 MHz, CDCh) 5: 1.42 (s, 9H), 2.1 (s, 2H), 2.22 (s, 2H), 2.27 (s, 2H), 4.53 (s, 2H), 6.67 (s, 1H).

[0205] Intermediate-20 : tert- Butyl 3-[amino(tert-butoxycarbonyl) amino] propanoate

[0206] Step-1: To a stirred solution of lert-butoxy-N-(l,3-dioxo-2,3-dihydro-lH- isoindol-2-yl)formamide (2.0 g, 7.62 mmol), potassium carbonate (2.1 g, 15.2 mmol) and benzyl triethyl ammonium chloride (0.35 g, 1.52 mmol) in ACN (40 mL), was added tert-butyl bromopropanoate (1.91 g, 9.15 mmol). The reaction mixture was heated at 55 °C for 24 hr till the completion of the reaction. The reaction was quenched with water (20 mL) and extracted using ethyl acetate (3 x 20 mL). The combined organic extracts were washed with water, brine and dried over sodium sulphate. The solvents were removed under reduced pressure and the crude product was purified by column chromatography with ethyl acetate and n-hexane to get tert-butyl 3-[tert- butoxycarbonyl-(l,3-dioxoisoindolin-2-yl)amino] propanoate.JH NMR (400 MHz, DMSO-de) 5: 1.23-1.45 (m, 18H), 2.53-2.57 (m, 2H), 3.76-3.76 (m, 2H), 7.93-7.99 (m, 4H). LCMS (ESI, m / z): 413.17 [M+Na]+.

[0207] Step-2: To a stirred solution of the product of Step-1 (1.68 g, 4.31 mmol) in DCM (20 mL), was added hydrazine hydrate (0.43 g, 8.62 mmol) and the reaction mixture was stirred overnight at RT. The reaction mixture was filtered and washed with DCM (2 x 20 mL) and the solvents were removed under reduced pressure to get crude material. The crude material was purified by silica gel column chromatography using ethyl acetate: n-hexane solvent to get intermediate - 20. 'H NMR (400 MHz, DMSO-de) 5: 1.37-1.42 (m, 18H), 3.88 (s, 2H), 4.50 (s, 2H). LCMS (ESI, m / z): 283.18 [M+Na]+.

[0208] Intermediate -21: tert- Butyl 4-{l-[(tert-butoxy)carbonyl]hydrazin-l-yl} butanoate

[0209] Step-1: To a stirred solution of tert-butoxy-N-(l,3-dioxo-2,3-dihydro-lH- isoindol-2-yl)formamide (2.0 g, 0.007 mol, 1.0 eq) and powdered potassium carbonate (4.2 g, 0.030 mol, 4.0 eq) in ACN (20 mb), was added benzyltriethylammonium chloride (0.17 g (0.0007 mol, O.leq) and tert-butyl 4-bromobutanoate (2.5 g, 0.0114 mol, 1.5 eq) and then stirred the reaction mixture at 60 °C for 24 hr. The completion of reaction was monitored by TLC analysis. The reaction mixture was fdtered and then concentrated the fdtrate to get the crude which was further column purified using mobile phase Hexane: Ethyl Acetate (80:20) to get tert-butyl 4-{[(tert- butoxy)carbonyl](l,3-dioxo-2,3-dihydro-lH-isoindol-2-yl)amino}butanoate. H NMR (400 MHz, DMSO-de) 5: 1.23 (s, 5H), 1.37 (s, 9H), 1.45 (s, 4H), 1.70-1.72 (m, 2H), 2.30-2.32 (m, 2H), 3.57 (m, 2H), 7.93-7.99 (m, 4H). LCMS (ESI, m / z): 427.2 [M+Na]+.

[0210] Step-2: To a stirred solution of the product of Step-1 (2.0 g, 0.005 mol, 1.0 eq) in Ethanol (40 mb), was added hydrazine hydrate (1.23 g, 0.025 mol, 5.0 eq) and then reaction mixture was stirred at RT for 16-20 hr. Completion of reaction was monitored by TLC. Filtered the reaction mixture through sintered funnel using whattmann paper and then concentrated the filtrate to get the crude which was further column purified using mobile phase Hexane: Ethyl Acetate (70:30) to get intermediate - 21. 'H NMR (400 MHz, DMSO-de) 5: 1.44 (s, 9H), 1.46 (s, 9H), 1.85 (quintet, J=1.0 Hz, 2H), 2.22 (t, J =7.37 Hz, 2H), 3.39 (t, .7=6,8 Hz, 2H), 3.97 (bs, 2H). LCMS (ESI, m / z): 297.2 [M+Na]+.

[0211] Intermediate-22: 2-[2-[[2-(2-tert-Butoxycarbonylhydrazino)-2-oxo-ethyl]- (2-tert-butoxy-2-oxo-ethyl)amino]ethyl]-5-methyl-pyrazole-3-carboxylic acid

[0212] Step-1: To a cooled solution of methyl 3-methyl-lH-pyrazole-5-carboxylate (0.62 g, 4.4 mmol), was added benzyl 2- {[2-(tert-butoxy)-2 -oxoethyl] (2- hydroxyethyl)amino} acetate (1.8 g, 5.5 mmol) and triphenylphosphine (2.19 g, 8.3 mmol) in THF (20 mb), was added DIAD (1.6 mb, 8.3 mmol) slowly dropwise. The reaction mixture was then stirred overnight at RT and the TLC analysis shows the completion of the reaction. The reaction mixture was concentrated to get crude material to which di -isopropyl ether (20 mL) was added and stirred for 15 min., and the solids were fdtered out and the fdtrate was adsorbed over silica gel and purified by column chromatography using ethyl acetate: hexane as gradient eluent to get desired product methyl 2-[2-[(2-benzyloxy-2-oxo-ethyl)-(2-tert-butoxy-2-oxo-ethyl)amino]ethyl]-5- methyl-pyrazole-3 -carboxylate.1H-NMR(400 MHz, CDCh) 5: 1.6 (s, 9H), 2.2 (s, 3H), 3.13 (m, 2H), 3.47 (s, 2H), 3.6 (s, 2H), 3.8 (s, 3H), 4.59 (m, 2H), 5.12 (s, 2H), 6.5 (s, 1H), 7.34 (m, 5H).

[0213] Step-2: To a solution of the product of Step-1 (1.3 g, 2.9 mmol) in methanol (20 mL), was added 10 % palladium on carbon (0.3 g) and was stirred under balloon pressure hydrogen atmosphere overnight at RT. After the completion of reaction by TLC analysis the reaction mixture was filtered over micron filter paper and filtrate was concentrated under vacuum to get 2-[(2-tert-butoxy-2-oxo-ethyl)-[2-(5- methoxycarbonyl-3-methyl-pyrazol-l-yl)ethyl]amino]acetic acid. LCMS (ESI, m / z): 356.15 [M+H]+.

[0214] Step-3: To a stirred solution of the product of Step-2 (1.05 g; 2.9 mmol) in DMF(15 mL), was added HATU (1.68 g; 4.4 mmol) and DIPEA (1.5 mL, 8.8 mmol) at 0 °C, followed by addition of tert-butyl carbazate (0.46 g; 3.5 mmol). The reaction mixture was allowed to stir at RT for 3hr. After the completion of the reaction by TLC analysis, the reaction mixture was concentrated under vacuum and the resulting crude obtained was purified by column chromatography to get methyl 2-[2-[[2-(2-tert- butoxycarbonylhydrazino)-2 -oxo-ethyl ]-(2-tert-butoxy-2-oxo-ethyl) amino] ethyl] -5- methyl-pyrazole-3 -carboxylate. 'H-NMR (400 MHz, DMSO-de) 5: 1.39 (s, 9H), 2.17 (s, 3H), 3.0 (m, 2H), 3.29 (s, 2H), 3.32 (s, 2H), 3.8 (s, 3H), 4.49 (m, 2H), 6.66 (s, 1H), 8.76 (s, 1H), 9.36 (s, 1H).

[0215] Step-4: To a stirred solution of the product of Step-3 (0.7 g, 1.5 mmol) in methanol (5 mL) and tetrahydrofiiran (6 mL) was added lithium hydroxide monohydrate (0.125 g, 3.0 mmol) in water (2 mL). The reaction mixture was stirredovernight at RT. The TLC analysis shows the completion of the reaction and the reaction mixture was acidified with amberlyst resin and filtered. The filtrate was dried over anhydrous sodium sulphate and then concentrated under vacuum to get intermediate - 22. LCMS (ESI, m / z): 456.33 [M+H]+.

[0216] Intermediate-23: l-[3-(tert-Butoxy)-3-oxopropyl]-3-methyl-lH-pyrazole- 5-carboxylic acid

[0217] Step-1: To a stirred solution of benzyl 3-methyl-lH-pyrazole-5-carboxylate (2 g, 9.2 mmol) in 1,2-dichloroethane (20 mb), was added tert-butyl acrylate (2 mL, 13.8 mmol) and silver carbonate (0.12 g, 0.46 mmol). The reaction mixture was heated to 120 °C for 24 hr. The reaction mixture was cooled to room temp and then filtered. The filterate was concentrated under vacuum and the crude was purified by column chromatography in ethyl acetate: hexane to get desired compound as benzyl l-[3-(tert- butoxy)-3-oxopropyl]-3-methyl-lH-pyrazole-5-carboxylate. 'H-NMR (400 MHz, CDCh) 5: 1.41 (s, 9H), 2.24 (s, 3H), 2.76 (t, J=1.38 Hz, 2H), 4.74 (t, J=1.38 Hz, 2H), 5.3 (s, 2H), 6.63 (s, 1H), 7.34-7.42 (m, 5H).

[0218] Step-2: To a stirred solution of the product of Step-1 (0.4 g, 1.31 mmol) in methanol (10 mL), was added Pd / C (10%) (80 mg) and the reaction mixture was stirred under hydrogen balloon pressure for 4 hr. The progress of reaction was monitored by TLC. On complete consumption of starting material on TLC, the reaction mixture was filtered and washed with methanol (5 mL). The filtrate was concentrated under vacuum resulting in intermediate - 23, which was used as such in next step.1H-NMR (400MHz, CDCh) 5: 1.42 (s, 9H), 2.27 (s, 3H), 2.79 (t, J=7.14 Hz, 2H), 4.75 (t, J=7.18 Hz, 2H), 6.7 (s, 1H).

[0219] Intermediate -24: tert- Butyl N-(2-aminoethyl)-N-[(2S,3R,4R,5R)-2,3,4,5,6- pentahydroxyhexyl] carbamate

[0220] Step-1: A stirred solution of D-glucamine (4.79 g, 26 mmol) and 2-(l,3-dioxo- 2,3-dihydro-lH-isoindol-2-yl)acetaldehyde (5 g, 26 mmol) in methanol (50 mL), was heated to reflux for 3 hr. The imine formation was ascertained by LC-MS. The reaction mixture was cooled to room temp and sodium triacetoxyborohydride (7.29 g, 34.4 mmol) was added in small portions under nitrogen. After overnight stirring at room temp, the reaction mixture was concentrated under vacuum and 1,4-dioxane (50 mL) and water (10 mL) was added, followed by addition of triethylamine (18 ml, 5 moles w.r.t 100% yield of amine) and di-tert-butyl dicarbonate (8.3 mL, 1.3 moles, 5 moles w.r.t 100% yield of amine). The reaction mixture was stirred for 5 hr at room temp and then concentrated under vacuum, the crude was then purified by column chromatography to get desired product tert-butyl N-[2-(l,3-dioxo-2,3-dihydro-lH- isoindol-2-yl)ethyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamate. LCMS (-ve mode, m / z): 453.15 [M-H]'.

[0221] Step-2: To a stirred solution of the product of Step-1 (0.7 g, 1.54 mmol) in ethanol (10 mL) was added hydrazine hydrate (0.3 g, 6.16 mmol). The reaction mixture was stirred at room temp and completion was monitored by LC-MS. Reaction mixture was filtered and concentrated under vacuum to give intermediate - 24. LCMS (ESI, m / z): 325.2 [M+H]+.

[0222] Intermediate-25: Methyl (4R,5S)-5-(aminomethyl)-2,2-dimethyl-l,3- dioxolane-4-carboxylate

[0223] Step-1: To a solution of methyl (4R,5S)-5-(hydroxymethyl)-2,2-dimethyl-l,3- dioxolane-4-carboxylate (0.25 g, 1.32 mmol) and triethylamine (0.28 mL, 1.98 mmol)in DCM (10 mL) at -10 °C, was added methane sulfonyl chloride (0. 12 mb, 1.58 mmol) and the reaction mixture was stirred for 30 min at 0 °C. TLC indicated complete conversion of starting material, after which, water (4 mL) was added to reaction mixture, organic layer was separated, washed with sat. sodium bicarbonate solution and brine. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated under vacuum resulting in yellow oil as methyl (4R,5S)-5- [(methanesulfonyloxy)methyl] -2,2-dimethyl- 1 ,3 -dioxolane-4-carboxylate .1H-N M R (400MHz, CDCh) 5: 1.43 (s, 3H), 1.49 (s, 3H), 3.08 (s, 3H), 3.82 (s, 3H), 4.35-4.39 (m, 1H), 4.40-4.44 (m, 2H), 4.53-4.57 (m, 1H).

[0224] Step-2: To a stirred solution of the product of Step-1 (0.35 g, 1.31 mmol) in DMF (4 mL), was added sodium azide (0.13 g, 1.96 mmol) and the reaction mixture was heated to 100 °C for 1 hr. TLC indicated complete conversion of starting material. The reaction mixture was filtered and concentrated under vacuum. The crude obtained was purified by column chromatography to get colourless oil as methyl (4R,5S)-5- (azidomethyl)-2,2-dimethyl- l,3-dioxolane-4-carboxylate.1H-NMR (400MHz, CDCh) 5: 1.44 (s, 3H), 1.52 (s, 3H), 3.34-3.39 (m, 1H), 3.70-3.74 (m, 1H), 3.79 (s, 3H), 4.30- 4.34 (m, 1H), 4.44 (d, J= 7.56 Hz, 1H).

[0225] Step-3: To a stirred solution of the product of Step-2 (0.22 g, 1.02 mmol) in methanol (4 mL), was added (10%) Pd / C (40 mg). The reaction mixture was stirred under hydrogen balloon pressure for two hours at room temp. The reaction mixture was filtered over micron paper and the filtrate was concentrated under vacuum resulting in intermediate -25. LCMS (ESI, m / z): 190.03 [M+H]+.

[0226] Intermediate-26: tert- Butyl 4-{[(2S,3R,4R,5R)-2,3,4,5,6- pentahydroxyhexyl] aminojbutanoate

[0227] Step-1: To a stirred solution of tert-Butyl 4-aminobutanoate (1 gm, 6.2 mmol) in 40 ml methanol, was added D-glucose (1.14 gm, 6.2 mmol) and heated the reaction mixture at 65 °C for 1 hr. The entire reaction mixture was then placed into miniclave vessel, added 0.6 gm of 10% Pd / C and stirred under 5 kg H2 gas pressure for overnight. Progress of reaction was monitored by LCMS. Thereafter the reaction mixture wasfdtered off through celite pad and fdterate was distilled off to get intermediate-26. LCMS (ESI, m / z): 324.28 [M+H]+.

[0228] In another embodiment, compounds of the present disclosure are compounds as set forth in the Examples in the draft.EXAMPLES:

[0229] The present disclosure is further illustrated in detail with reference to the following examples. It is desired that the examples be considered in all respect as illustrative and are not intended to limit the scope of the claimed invention. The compounds according to the present disclosure may be prepared by process as described below.

[0230] Compound P.l:

[0231] Step-1: To a solution of Intermediate-14 (0.5 g, 0.81 mmol) in DMF (5 mL), was added 1 -(3 - { N'- 1 ( / c / V-biitoxy [carbonyl | -hydrazinecarbonyl }propyl)-3 -methyl- 1H- pyrazole-5 -carboxylic acid (15) (0.5 g, 1.46 mmol) under inert atmosphere, followed by HATU (0.56 g, 1.46 mmol), DIPEA (0.28 mL, 1.63 mmol) at ambient temperature and was allowed to stir for 3 hr. The reaction mixture was quenched with aqueous sodium bicarbonate solution, filtered and concenterated under reduced pressure to afford crude product which was purified by RP-HPLC using following condition: Column C18, mobile phase-A (0.1% TFA in water) and mobile phase-B (0.1% TFA in ACN); Detector UV 254 / 323 nm to get P.l.a,1H NMR (400 MHz, DMSO-de) 5: 1.24 (m, 3H), 1.43 (s, 9H), 1.99-2.04 (m, 2H), 2.11-2.18 (m, 8H), 2.31-2.38 (m, 2H), 4.30- 4.38 (m, 4H), 4.56-4.59 (m, 4H), 4.85-4.90 (m, 4H), 5.41-5.50 (m, 2H), 6.40-6.50 (m, 2H), 7.10-7.17 (m, 2H), 7.30-7.37 (m, 2H), 7.70-7.79 (m, 4H), 8.74(s, 1H), 9.60 (s, 1H). LCMS (ESI, m / z): 921.53 [M+H]+(observed); Calculated for C44H52N14O9: 920.4 (M).

[0232] Step-2: To a solution of P.l.a (0.045 g, 0.048 mmol) in DCM (1 mL) under nitrogen atmosphere, was added TFA ( 1 mL) and stirred at ambient temperature for 2 hr. The solvent was removed under reduced pressure and co-distilled using DCM. The residue was mixed with ethyl acetate (10 mL), stirred for 10 min and filtered. To the solid residue, diethyl ether was added, stirred, again filtered and dried under suction to get compound of formula P.l as trifluoro acetate salt.1H NMR (400 MHz, DMSO-de) : 5 1.31 (t, J=7.02 Hz, 3H), 2.00-2.04 (m, 2H), 2.12 (s, 6H), 2.12-2.20 (m, 2H), 2.30- 2.40 (m, 2H), 4.40-4.48 (m, 4H), 4.50-4.58 (m, 4H), 4.94-5.00 (s, 4H), 5.50-5.55 (m, 2H), 6.61 (s, 1H), 6.64 (s, 1H), 7.44 (s, 2H), 7.58 (s, 2H), 7.76 (s, 2H), 8.06 (s, 2H), 10.11 (s, 1H), 12.94 (bs, 2H). LCMS (ESI, m / z): 821.54 [M+H]+(observed value); Calculated for C39H44N14O7: 820.35 (M).

[0233] Compound P.2:

[0234] Step-1: Using intermediate - 16 (78 mg, 0.2 mmol) and intermediate - 14 (0. 1 g, 0.16 mmol) and following the procedure as described for Compound P.l.a, the desired compound P.2.a was synthesized. LCMS(ESI, m / z): 935.5 [M+H]+; Calculated for C45H54N14O9: 934.3 (M).

[0235] Step-2: To a stirred solution of P.2.a (35 mg, 0.0374 mmol) in 2 ml DCM was added TFA (0.2 mL) at 0 °C and then stirred the reaction mixture at RT for 1 hr. The LCMS analysis shows the completion of reaction and the reaction mixture was concentrated under vacuum and the crude product obtained was triturated with diethyl ether to get TFA salt of P.2.1H NMR (400 MHz, DMSO-de) 5: 1.28 (t, J=1.02 Hz, 3H), 2.0-2. 1 (m, 2H), 2.09 (s, 6H), 2.1-2.2 (m, 2H), 2.25-2.35 (m, 2H), 2.7 (s, 3H), 4.4- 4.45 (m, 4H), 4.5-4.58 (m, 4H), 4.9 (s, 4H), 5.4-5.55 (m, 2H), 6.58 (s, 1H), 6.61 (s, 1H), 7.42 (s, 2H), 7.55 (s, 2H), 7.73 (s, 2H), 8.04 (s, 2H), 10.93 (s, 1H), 12.9 (bs, 2H). LCMS (ESI, m / z): 835.49 [M+H]+(observed value); Calculated for C40H46N14O7: 834.36 (M).

[0236] Compound P.3:

[0237] Step-1: Using intermediate - 17 (0.124 g, 0.00032 mol) and intermediate-14 (0.1 g, 0.00016 mol) and following the procedure as described for compound P.l.a, the desired crude product was obtained, which was further purified by silica gel column chromatography eluting with MeOH: DCM (5-10%) and aqueous ammonia (2%) to yield compound P.3.a. 'H NMR (400 MHz, DMSO-de) 5: 1.33-1.3 (m, 3H), 1.44 (s, 9H), 2.13 (s, 6H), 2.35 (m, 2H), 3.55 (m, 4H), 3.77 (t, J=6.2 Hz, 2H), 3.93 (s, 2H), 4.48 (m, 4H), 4.59 - 4.57 (m, 2H), 4.75 (m, 2H), 4.94 (m, 4H), 5.54 (bs, 2H), 6.63-6.61 (d, .7=7,7 Hz, 2H), 7.45 (s, 2H), 7.59 (s, 2H), 7.77 (s, 2H), 8.07 (s, 2H), 8.8 (s, 1H), 9.52 (m, 1H), 12.86 (bs, 2H). LCMS ESI (m / z): 981.56 [M+H]+; Calculated for C46H56N14O11: 980.4 (M).

[0238] Step-2: To a solution of P.3.a (60 mg, 0.06 mmol) in DCM (5 m ) was added TFA (0.3 mb) dropwise. The resulting solution was stirred at RT for 5 hr. The reaction mixture was concentrated under reduced pressure. The crude obtained was purified by RP-HPLC using Column C18, mobile phase-A (0.1% Ammonium bicarbonate in water) and mobile phase-B (ACN); Detector UV 254 / 323 nm and pure product was obtained on freeze drying as P.3.JH NMR (400 MHz, DMSO-de) 5: 1.3 (t, J=7.0 Hz, 3H). 2.12 (s, 6H), 2.3-2.4 (m, 2H), 3.5-3.55 (m, 4H), 3.6-3.7 (m, 2H), 3.85-3.9 (m, 2H), 4.4-4.5 (m, 4H), 4.52-4.62 (m, 2H), 4.7-4.8 (m, 2H), 4.94 (s, 4H), 5.5-5.53 (m, 2H), 6.60 (s, 1H), 6.62 (s, 1H), 7.45 (s, 2H), 7.58 (s, 2H), 7.76 (s, 2H), 8.07 (s, 2H), 8.91 (bs, 1H). LCMS (ESI, m / z): 881.41 [M+H]+; Calculated for C41H48N14O9: 880.37 (M).

[0239] Compound P.4:

[0240] Step-1: To a solution of intermediate - 18 (0.21 g, 0.49 mmol) in DMF (2 mL), under nitrogen atmosphere, were added HATU (0.18 g, 0.49 mmol) and DIPEA (0.085 ml, 0.40 mmol) at RT and the mixture was stirred for 15 min. Intermediate - 14 (0.5g, 0.81 mmol) was added and the stirring was continued at RT for 3 hr. The reaction mixture was quenched with aqueous sodium bicarbonate solution and the solid precipitated was fdtered and dried under reduced pressure to afford a light brown solid. The crude product was subjected to RP-HPLC using following condition, Column Cl 8, mobile phase-A (0.1% TFA in water) and mobile phase-B (0.1% TFA in ACN), Detector UV 254 / 323 nm, to isolate P.4.a. 'H NMR (400 MHz, DMSO-de) 5: 1.21 (t, J=7.1 Hz, 3H), 1.30 (s, 9H), 1.37 (s, 9H), 1.90-2.0 (m, 2H), 2.05-2.15 (m, 8H), 2.25- 2.35 (m, 2H), 3.90-4.0 (m, 2H), 4.30-4.45 (m, 4H), 4.45-4.65 (m, 4H), 4.86 (s, 4H),5.40-5.42 (m, 2H), 6.44 (s, 1H), 6.46 (s, 1H), 7.26 (bs, 2H), 7.42 (bs, 2H), 7.72 (s, 1H), 7.73 (s, 1H), 7.90 (s, 2H), 10.14 & 10.19 (two s, 1H), 12.82 (bs, 2H). LCMS (ESI, m / z): 1035.63 [M+H]+(observed value); Calculated for C50H62N14On: 1034.3 (M).

[0241] Step-2: To a compound P.4.a (0.034 g, 0.032 mmol) cooled in ice-bath under nitrogen atmosphere, was added pre-cooled TFA: DCM (1: 1) (1 mL) mixture at 0-10 °C dropwise and was stirred for 4 hr at same temperature. Progress of reaction was monitored using UPLC-MS. The solvent was removed under reduced pressure and codistilled using DCM. 10% MeOH-Ethyl acetate (10 mL) was added, stirred for 15 min and fdtered the mixture to obtain a solid mass. The solid mass was washed with ACN (10 mL), ethyl acetate (10 mL) and finally titurated with diethyl ether (10 mL) and dried under high vacuum to obtain TFA salt of P.4. 'H NMR (400 MHz, DMSO-de) 5: 1.25 (t, J=6.00 Hz, 3H), 1.90-2.00 (m, 4H), 2.06 (s, 6H), 2.20-2.30 (m, 2H), 3.47 (s, 2H),4.40-4.50 (m, 4H), 4.50-4.60 (m, 4H), 4.88 (s, 4H), 5.45 - 5.55 (m, 2H), 6.56 (s, 1H), 6.57 (s, 1H), 7.40 (s, 2H), 7.52 (s, 2H), 7.70 (s, 2H), 8.02 (s, 2H), 9.55 (s, 1H), 12.90(bs, 2H, partially exchanged). LCMS (ESI, m / z): 879.56 [M+H]+(observed value);Calculated for C41H46N14O19: 878.35 (M).

[0242] Compound P.5:

[0243] Step-1 : To a stirred solution of intermediate - 19 (0.65 g, 0.002 mol) and HATU (0.97 g; 0.0025 mol) in DMF (20 mL) was added DIPEA (0.72 mL, 0.004 mol) to give clear solution. Then cooled the reaction mixture to 0-5 °C and charged with intermediate - 14 (1.0 g, 0.0016 mol) then stirred the reaction mixture at 25-30 °C for 20 hr. The TLC analysis shows the completion of the reaction. After completion of reaction the reaction mixture was poured into water (200 mL) and stirred for 30-45 min. The solids precipitated out was filtered through cloth and wash with water. The solids obtained were triturated in diethyl and stirred in ethyl acetate at 40-45 °C for 15 min., and filtered. The solids obtained were dried under reduced pressure to get P.5.a. LCMS (ESI, m / z): 863.53 [M+H]+(observed value); Calculated for C43H50N12O8: 862.39 (M).

[0244] Step-2: To a stirred solution of P.5.a (1.2 gm, 0.0013 mol) in 5 mL DCM was added 5 mL TFA to give clear solution. Then stirred the reaction mixture at 25-30 °C for 16-20 hours. After this time, the reaction was checked for completion by TLC. After completion of reaction, concentrate reaction mixture under reduced pressure to get solid. Leach the solid obtained in diethyl ether 2-3 times. Then leach the solid in ACN,stir at 30-40 °C for 15-30 minutes, filtered the solid to get P.5.b.JH NMR (400 MHz, DMSO-de) 5: 1.31 (t, J =7. 10 Hz, 3H), 1.95-2.05 (m, 2H), 2.12 (s, 6H), 2.15-2.25 (t, J=7.30 Hz, 2H), 2.30-2.40 (m, 2H), 4.45-4.52 (m, 4H), 4.52-4.65 (m, 4H), 4.93 (s, 4H), 4.95-5.55 (m, 2H), 6.61 (s, 1H), 6.62 (s, 1H), 7.44 (s, 2H), 7.58 (s, 2H), 7.76 (s, 2H), 8.06 (s, 2H), 12.94 (bs, 2H). LCMS (ESI, m / z): 807.4 [M+H]+(observed value); Calculated for C,qH49N19O„: 806.32 (M).

[0245] Step-3: To a stirred solution of P.5.b (0.1 g, 0.12 mmol) in DMF (2 mL) was added HATU (54 mg, 0.14 mmol), DIPEA (0.04 mL, 0.24 mmol) and tert-butyl 3-{ l- [(tert-butoxy)carbonyl] hydrazin-l-yl}propanoate intermediate-20 (39 mg, 0.14 mmol) at RT and then allowed to stir at same temperature for 2 hr. The completion of reaction was confirmed by LCMS and then the reaction mixture was poured into water (20 mL) and stirred for 15 min. and the separated out solid was filtered and further purified by RP-HPLC using Column C18, mobile phase-A (0.1% TFA in water) and mobile phase- B (0.1% TFA in ACN); Detector UV 254 / 323nm to get P.5.c. LCMS (ESI, m / z): 1049.63 [M+H]+(observed value); Calculated for C51H64N14On: 1048.48 (M).

[0246] Step-4: Stirred solution of P.5.c (65 mg, 0.061 mmol) in DCM (1 mL) and TFA (1 mL) at 0-5 °C for 15 mins and allowed to stir at RT for 2 hr. Completion of reaction was monitored by LCMS, the volatiles were distilled off and triturated the crude by diethylether to get TFA salt of P.5.1H NMR (400 MHz, DMSO-de) 5: 1.26 (t, J=7.04 Hz, 3H), 1.95-2.01 (m, 2H), 2.07 (s, 6H), 2.07-2.15 (m, 2H), 2.25-2.35 (m, 2H), 2.5- 2.6 (m, 2H), 3.09 (t, .7=6 Hz, 2H), 4.4-4.45 (m, 4H), 4.5-4.53 (m, 4H), 4.88 (s, 4H), 5.45-5.55 (m, 2H), 6.56 (s, 1H), 6.59 (s, 1H), 7.4 (bs, 2H), 7.53 (s, 2H), 7.71 (s, 2H), 8.02 (bs, 2H), 10.38 (bs, 1H, partially exchanged), 12.92 (bs, 2H, partially exchanged). LCMS (ESI, m / z): 893.52 [M+H]+(observed value); Calculated for C42H48N14O9: 892.37 (M).

[0247] Compound P.6:

[0248] Step-1: To a stirred solution of P.5.b (100 mg, 0.12 mmol, 1.0 eq) and HATU (54 mg, 0.14 mmol, 1.2 eq) in DMF (2 mL) was added DIPEA (0.04 mL, 0.24 mmol, 2.0 eq) and intermediate - 21 (40 mg, 0.14 mmol) at 0-5 °C, and then reaction mixture was stirred at RT for 2 hr. Completion of reaction was monitored by TLC and the reaction mixture was quenched in water (25 mL) under stirring. The solid observed was fdtered, dried under vacuum at 50 °C and purified by RP-HPLC using Column C18, mobile phase-A (0.1% TFA in water) and mobile phase-B (0.1% TFA in ACN); Detector UV 254 / 323 nm, to get (P.6.a). 'H NMR (400 MHz, DMSO-de) 5: 1.30 (t, .7=6.91 Hz, 3H), 1.41 (m, 9H), 1.30-1.50 (m, 9H), 1.60-1.75 (m, 2H), 2.12 (s, 6H), 2.0- 2.15 (m, 2H), 2.20-2.30 (m, 2H), 2.30-2.40 (m, 2H), 2.60-2.70 (m, 2H), 4.48 (s, 4H), 4.50-4.65 (m, 4H), 4.94 (s, 4H) , 5.50-5.65 (m, 2H), 6.61 (s, 1H), 6.64 (s, 1H), 7.43 (s, 2H), 7.58 (s, 2H), 7.65-7.75 (m, 1H), 7.76 (s, 2H), 8.06 (s, 2H), 9.93 (bs, 1H), 12.93 (bs, 2H). LCMS (ESI, m / z): 1063.5 [M+H]+(observed value); Calculated for C52H66N14On: 1062.5 (M).

[0249] Step-2: The pre-cooled solution of TFA: DCM (2 mL; 1: 1) was added P.6.a (0.026 g, 0.024 mmol) at 0-10 °C, under nitrogen atmosphere and stirred at same temperature for 2 hr. Completion of reaction was monitored using UPLC-MS. The solvent was removed under reduced pressure and co-distilled using DCM. Diethyl ether was added stirred for 5 min., then fdtered and dried to obtain TFA salt of P.6.JH NMR (400 MHz, DMSO-de) : 5 1.31 (t, J=7.1 Hz, 3H), 1.74-1.83 (m, 2H), 2.04-2.07 (m, 2H), 2.12 (s, 6H), 2.15-2.24 (m, 2H), 2.32-2.41 (m, 4H), 3.01-3.06 (m, 2H), 4.44-4.52 (m, 4H), 4.53-4.62 (m, 4H), 4.94 (s, 4H), 5.53-5.57 (m, 2H), 6.61 (s, 1H), 6.65 (s, 1H), 7.46 (s, 2H), 7.58 (s, 2H), 7.76 (s, 2H), 7.81 (s, 1H), 8.08 (s, 2H), 10.80 (s, 1H), 12.94 (bs, 2H, partially exchanged). LCMS (ESI, m / z): 907. 29 [M+H]+(observed value); Calculated for C43H50N14O9: 906.38 (M).

[0250] Compound P.7:

[0251] Step-1: To an ice-cooled solution of intermediate - 22 (0.148 g, 0.32 mmol) in DMF (10 mL) was added HATU (0.12 g, 0.32 mmol), DIPEA (0.1 mL, 0.64 mmol) and after 5 min, intermediate - 14 (0.1 g, 0.16 mmol) in small portions. The resulting solution was stirred at RT overnight. The reaction mixture was concentrated under vacuum and then treated with ethyl acetate (10 mL), the crude solid obtained was filtered and dried under vacuum. The crude solid was purified by RP-HPLC using Column C18, mobile phase-A (0.1% TFA in water) and mobile phase-B (0. 1% TFA in ACN); Detector UV 254 / 323 nm, to obtain P.7.a. 'H NMR (400 MHz, DMSO-de) 5: 1.28-1.35 (m, 12H), 1.38 (s, 9H), 2.12 (s, 3H), 2. 13 (s, 3H), 2.32-2.38 (m, 2H), 3.2 (m, 2H), 3.30-3.34 (m, 1H), 3.40-3.50 (m, 1H), 3.62-3.72 (m, 2H), 4.45-4.52 (m, 4H), 4.52-4.62 (m, 2H), 4.65-4.75 (m, 2H), 4.94 (bs, 4H), 5.54 (bs, 2H), 6.62 (s, 1H), 6.66 (s, 1H), 7.46 (s, 2H), 7.59 (s, 2H), 7.77 (s, 2H), 8.07 (s, 2H), 8.20-8.35 (m, 1H), 8.85 (s, 1H), 9.7 (s, 1H), 12.9 (bs, 2H). LCMS (ESI, m / z): 1050.6 [M+H]+(observed value); Calculated for C50H63N15On: 1049.48 (M).

[0252] Step-2: To an ice-cooled suspension of P.7.a (25 mg, 0.02mmol) in DCM (5 mL) was added TFA (0.4 mL) slowly dropwise. The reaction mixture was stirred overnight, the progress of reaction was monitored by UPLC-MS. On completion of reaction, mixture was concentrated and then treated with diethyl ether, filtered and dried under vacuum and then purified by RP-HPLC using column Cl 8, mobile phase-A (0.1% TFA in water) and mobile phase-B (0.1% TFA in ACN); Detector UV 254 / 323 nm, to obtain TFA salt of P.7. 'H NMR (400 MHz, DMSO-de) 5: 1.3 (m, 3H), 2.13 (s, 6H), 2.35 (m, 3H), 3.13 (m, 2H), 3.35-3.50 (m, 2H), 3.50-3.60 (m, 2H), 4.49 (m, 4H), 4.57 (m, 2H), 4.69 (m, 2H), 4.94 (s, 4H), 5.50-5.60 (m, 2H), 6.62 (s, 1H), 6.66 (s, 1H), 7.46 (s, 2H), 7.59 (s, 2H), 7.77 (s, 2H), 8.09 (s, 2H), 10.6 (bs, 1H), 12.9 (bs, 2H, partially exchanged). LCMS (ESI, m / z): 894.52 [M+H]+(observed value); Calculated for C41H47N15O9: 893.36 (M).

[0253] Compound P.8:

[0254] Step-1: To a stirred solution of P.5 (15 mg, 0.016 mol, 1.0 eq) in DMF (0.5 mb), were added N-methyl-D-glucamine (6.6 mg, 0.03 mol, 2 eq), HATU (8.1 mg, 0.02 mol, 1.3 eq) and DIPEA (8 mg, 0.064 mol, 4 eq) at rt. After 2 hours of stirring, when completion of the reaction was indicated by LCMS, the solvent was distilled off. The crude was purified by RP-HPLC using Column C18, mobile phase-A (0.1% TFA in water) and mobile phase-B (0.1% TFA in ACN), Detector UV 254 / 323 nm, to obtain the desired compound P.8 as TFA salt.1H NMR (400 MHz, DMSO-de) 5: 1.26 (t, J=7.1 Hz, 3H), 1.9-2.05 (m, 2H), 2.07 (s, 6H), 2.1-2.2 (m, 2H), 2.25-2.35 (m, 2H), 2.55 (t, J= 5.6 Hz, 2H), 2.65-2.7 (m, 1H), 2.83 & 2.97 (two s, 3H), 3.18-3.32 (m, 2H), 3.35- 3.55 (m, 4H), 3.55-3.65 (m, 2H), 3.75-3.82 (m, 1H), 4.40-4.50 (m, 4H), 4.50-4.60 (m, 4H), 4.89 (bs, 4H), 5.45-5.55 (m, 2H), 6.56 (s, 1H), 6.6 (s, 1H), 7.4 (s, 2H), 7.54 (s, 2H), 7.71 (s, 2H), 8.02 (s, 2H), 8.34 (bs, 1H), 10.8-11.1 (two bs, 1H), 12.9 (bs, 2H, partially exchanged). LCMS (ESI, m / z): 1070.53 [M+H]+(observed value); Calculated for C49H63N15O13: 1069.47 (M).

[0255] Compound P.9 :

[0256] Step-1: Starting from P.5 (200 mg, 0.16 mmol) and D-glucamine (34 mg, 0.19 mmol) and following the procedure as described for compound P.8, the desired compound P.9 was obtained as TFA salt. 'H NMR (400 MHz, DMSO-de) 5: 1.31 (t, .7=7,0 Hz, 3H), 1.95-2.10 (m, 3H), 2.12 (s, 6H), 2.25-2.40 (m, 3H), 2.55-2.65 (m, 2H), 2.85-3.0 (m, 2H), 3.0-3.75 (m, 8H), 4.4-4.55 (m, 4H), 4.55-4.65 (m, 4H), 4.9-5.05 (bs,4H), 5.45-5.65 (m, 2H), 6.61 (s, 1H), 6.63 (s, 1H), 7.44 (bs, 2H), 7.58 (s, 2H), 7.76 (s, 2H), 7.9-7.98 (m, 1H), 8.07 (bs, 2H), 9.53 (bs, 1H), 12.93 (bs, 2H). LCMS (ESI, m / z): 1056.62 [M+H]+(observed value); Calculated for C48H61N15O13: 1055.45 (M).

[0257] Compound P.10:

[0258] Step-1: To a stirred solution of intermediate - 23 (0.24 g, 0.98 mmol) in DMF (20 mL), were added HATU (0.46g, 1.23mmol) and DIPEA (0.42 mL, 2.46mmol). After stirring for 5 min, intermediate - 14 (0.5 g, 0.82 mmol) was added portion wise. The reaction mixture was stirred overnight at room temp. The reaction mixture was then concentrated under vacuum and the crude obtained was treated with ACN, filtered, washed with diethyl ether and dried to give P.IO.a. which was used in next step without further purification. LCMS (ESI, m / z): 849.54 [M+H]+, Calculated for C42H48N12O8; 848.37(M)

[0259] Step-2: To an ice cooled suspension of P.IO.a (500 mg, 0.59 mmol) in DCM (15 mL), was added TFA (2.5 mL) slowly dropwise under nitrogen. The reaction mixture was stirred at room temp for 4 hr. The progress of reaction was monitored by LC-MS. Upon completion reaction mixture was concentrated under vacuum and co distilled with toluene. The crude obtained was triturated with diethyl ether (2 x 15 mL), ether was decanted and the solid obtained was dried under vacuum for Ihr. The crude brown solid obtained as P.lO.b was used in next step without any further purification. LCMS (ESI, m / z): 793.42 [M+H]+, Calculated for C38H40N12O8: 792.3 (M).

[0260] Step-3: To a stirred solution of P.lO.b (0.3 g, 0.38 mmol) in DMF (8 mL), were added HATU (0.21 g, 0.57 mmol) and DIPEA (0.32 mL, 1.9 mmol), followed by addition of intermediate - 24 (0.18 g, 0.57 mmol). The reaction mixture was stirred for 1 hr at room temp and was monitored by LC-MS. The reaction mixture was concentrated under vacuum, the crude obtained was treated with ACN and the resulting brown solid was filtered, washed with acetontirile, methanol and diethyl ether. The solid was dried under vacuum to get P.lO.c and used in next step without any further purification. LCMS (ESI, m / z): 1099.5 [M+H]+, Calculated for C51H66N14O14: 1098.48 (M)

[0261] Step-4: To an ice cooled mixture of P.lO.c (0.2 g, 0.18 mmol) in DCM (10 mL), was added TFA (1 mL) slowly dropwise. The reaction mixture was stirred at room temp for 3 hr. The progress of reaction was monitored by LC-MS. On completion reaction mixture was concentrated under vacuum, the crude obtained was treated with diethyl ether resulting in brown solid, which was filtered and dried under vacuum. The crude solid was purified by RP-HPLC using Column C18, mobile phase-A (0.1% TFA in water) and mobile phase-B (0.1% TFA in ACN); Detector UV 254 / 323 nm and pure product containing fractions were freeze dried to get TFA salt of P.10.1H-NMR (400 MHz, DMSO-de) 5: 1.25 (t, J=7.06 Hz, 3H), 2.07 (s, 6H), 2.25-2.35 (m, 2H), 2.55-2.7 (m, 2H), 2.85-3.05 (m, 2H), 3.2-3.7 (m, 6H), 3.8-3.95 (m, 2H), 4.35-4.45 (m, 4H), 4.45- 4.60 (m, 2H), 4.70-4.75 (m, 2H), 4.80-5.0 (bs, 4H), 5.4-5.60 (m, 2H), 6.55 (s, 1H), 6.58 (s, 1H), 7.40 (s, 2H), 7.53 (s, 2H), 7.71 (s, 2H), 8.03 (s, 2H), 8.05-8.15 (m, 1H), 8.40 (bs, 2H), 9.14 (bs, 2H), 12.91 (bs, 2H). LCMS (ESI, m / z): 999.63 [M+H]+(observed), Calculated for C46H58N14O12: 998.43 (M)

[0262] Compound P.il:

[0263] Step-1: To a stirred solution of P.5 (0.25 g, 0.2 mmol) and methyl (4S,5R)-5- (aminomethyl)-2,2-dimethyl-l,3-dioxolane-4-carboxylate intermediate -25 (50 mg, 0.26 mmol) in DMF (5 mL), was added DIPEA (0.17 mL, 1 mmol) followed by HATU(91 mg, 0.24 mmol). The reaction mixture was stirred for 1 hr at room temp. The progress of reaction was monitored by LC-MS. The reaction mixture was concentrated under vacuum, the crude obtained was treated with ethyl acetate and then filtered, washed with diethyl ether and then dried under vacuum to get P.ll.a which was used in next step without further purification. LCMS (ESI, m / z): 1064.69 [M+H]+, calculated for C50H61NISO12: 1063.46 (M).

[0264] Step-2: To a stirred solution of P.ll.a (0.2 g), was added TFA: water (9: 1) 2 mL at RT. The reaction mixture was stirred for 20 min at RT. The progress of reaction was monitored by LC-MS. Reaction mixture was concentrated under vacuum, the crude ketal compound, thus obtained, was treated with diethyl ether and the solid was fdtered, dried and then again mixed in 4 mL of THF: MeOH (1: 1), followed by addition of lithium hydroxide (31 mg in ImL water). The resulting solution was stirred at room temp for one hour. The progress of reaction was monitored by LC-MS. The reaction mixture was cooled in ice bath and acidified with 4M HC1 in dioxan and then concentrated under vacuum. The crude obtained was treated with diethyl ether and filtered. RP-HPLC was performed using Column C18, mobile phase-A (0.1% TFA in water) and mobile phase-B (0.1% TFA in ACN); Detector UV 254 / 323 nm, to get the pure fractions which were lyophilized to get TFA salt of P.ll. 'H-NMR (400 MHz, DMSO-de) 5: 1.26 (t, J=7.1 Hz, 3H), 1.95-2.05 (m, 2H), 2.07 (s, 6H), 2.10-2.20 (m, 2H), 2.25-2.35 (m, 2H), 2.55-2.65 (m, 2H), 3.05-3.15 (m, 2H), 3.15-3.25 (m, 2H), 3.5- 4.2 (m, 2H), 4.40-4.48 (m, 4H), 4.50-4.60 (m, 4H), 4.88 (bs, 4H), 5.45-5.55 (m, 2H), 6.56 (s, 1H), 6.59 (s, 1H), 7.40 (bs, 2H), 7.53 (s, 2H), 7.71 (s, 2H), 8.02 (bs, 2H), 8.12- 8.20 (m, 1H), 10.7-11.0 (two s, 1H), 12.91 (bs, 2H). LCMS (ESI, m / z): 1010.65 [M+H]+(observed); Calculated for C46H55N15O12: 1009.41 (M).

[0265] Compound P.12 :

[0266] Step-1: To a stirred solution of P.4 (0.38 g, 0.3 mmol) in DMF (8 mL) was added intermediate-26 (0.2 g, 0.6 mmol) in DMF (2 mL) followed by DIPEA (0.26 mL,1.4 mmol) and HATU (0.15 g, 0.39 mmol). The reaction mixture was stirred at room temp for 30 min, the progress of reaction was monitored by LC-MS. On completion of reaction, mixture was concentrated under vacuum, the crude obtained was treated with ACN (10 mL) resulting in brown solid (P.12.a), which was filtered and washed with diethyl ether, dried under vacuum and used in next step without any further purification.

[0267] The crude P.12.a (0.28 g) was taken in DCM (1.5 mL), cooled in ice bath and a (1: 1) mixture of DCM and TFA (3 mL) was added dropwise. Progress of reaction was monitored by LC-MS. Reaction mixture was concentrated under vacuum at 35 °C, the crude obtained was treated with diethyl ether resulting in brown solid which was fdtered, dried under vacuum and then purified by RP-HPLC using Column C 18, mobile phase-A (0.1% Ammonium bicarbonate in water) mobile phase-B (ACN), Detector UV 254 / 323 nm, and the pure fractions obtained were lyophilized to get the final compound P.12. 'H-NMR (400 MHz, DMSO-de) 5: 1.26 (t, J=7.1 Hz, 3H), 1.65-1.75 (m, 2H), 1.90-2.05 (m, 4H), 2.07 (s, 6H), 2.10-2.25 (m, 2H), 2.25-2.35 (m, 2H), 2.42- 2.48 (m, 2H), 3.25-3.60 (m, 8H), 3.80-3.95 (m, 1H), 4.20-4.35 (m, 2H), 4.35-4.45 (m, 4H), 4.45-4.55 (m, 4H), 4.88 (s, 4H), 4.97 (bs, 3H), 5.40-5.60 (m, 2H), 6.55 (s, 1H), 6.57 (s, 1H), 7.36 (bs, 2H), 7.52 (s, 2H), 7.70 (s, 2H), 7.99 (bs, 2H), 9.25 (bs, 1H). LCMS (ESI, m / z): 1128.62 [M+H]+(observed); Calculated for C51H65N15O15: 1127.48 (M).

[0268] Construct C.l:

[0269] DIPEA (0.024 mL, 0.16 mmol) and HOBt (0.002 g, 0.014 mmol) were sequentially added to a stirred solution of Intermediate-II, prepared by the process disclosed below, (0.055 g, 0.038 mmol) and compound of formula P.l (0.030 g, 0.025 mmol) in DMF (1.5 mL) at RT and the resultant reaction mixture was then stirred at RT for 24 hrs. The reaction mixture was then diluted with 15 mL diethyl ether andcontents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the crude residue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, Cl 8, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.l as a di-trifluoroacetate salt. LCMS (ESI, m / z): 1060.48 [M+2H]2+ / 2, 707.50 [M+3H]3+ / 3 (observed value); Calculated for C98H139N23O30; 2118.00 (M).

[0270] Synthesis of {4-[(2S)-5-(carbamoylamino)-2-[(2S)-2-[(2S)-2-{l-[3-(2,5- dioxo-2,5-dihydro -lH-pyrrol-l-yl)propanamido]-3,6,9,12-tetraoxapentadecan- 15-amido}-4-[(2,5,8,ll,14,17,20,23-octaoxapentacosan-25-yl)carbamoyl] butanamido]-3-methylbutanamido]pentanamido]phenyl}methyl 4-nitrophenyl carbonate (Intermediate-II):

[0271] Step 1: Synthesis of benzyl (2S)-2-{[(benzyloxy)carbonyl]amino}-4- [(2,5,8,ll,14,17,20,23-octaoxapentacosan-25-yl)carbamoyl]butanoate

[0272] DIPEA (6.5 mL,37 mmol) and TBTU (7.3 g, 22 mmol) were sequentially added to a stirred solution of 2-[2-[2-[2-[2-[2-[2-(2- methoxy ethoxy )ethoxy] ethoxy] ethoxy] ethoxy] ethoxy] ethoxy] ethanamine (5.78 g, 15 mmol) and 5-benzyloxy-4-(benzyloxycarbonylamino)-5-oxo-pentanoic acid (5.6 g, 15mmol) in DMF (60 mb) at RT and stirred overnight for 18h at ambient temperature. The resultant reaction mixture was diluted with 200 ml ethyl acetate and quenched with 80 ml DM water. After separation of organic and aqueous layers, the aqueous layer was once again extracted with 100 ml ethyl acetate. Combined organic layer was washed with brine solution, dried over anhydrous sodium sulphate and concentrated in vacuo at 50 °C. The residue was chromatographed on silica-gel (230-400 mesh) using (05:95) Methanol DCM as the eluent to obtain of benzyl (2S)-2- {[(benzyloxy)carbonyl]amino}-4-[(2,5,8,l l,14,17,20,23-octaoxa pentacosan-25-yl)carbamoyl]butanoate. LCMS (ESI, m / z) 737.41 [M+H]+(observed value); Calculated for C37H56N2O13; 736.37 (M).

[0273] Step 2: Synthesis of (2S)-2-amino-4-[(2,5,8,ll,14,17,20,23- octaoxapentacosan-25-yl)carbamoyl]butanoic acid

[0274] 10% Palladium on charcoal (50% wet) (1.6g) was added to a stirred solution of the product obtained in Step-1 (7.9 g, 10 mmol) in methanol (80 mL). Reaction mixture was stirred under hydrogen pressure applied through a balloon fdled with hydrogen gas at RT for 3 hrs. Reaction mixture was filtered through celite bed and washed with methanol (2x50 mL). Combined filtrate was concentrated under reduced pressure to get title compound. LCMS (ESI, m / z) 513.29 [M+H]+(observed value); calculated for C22H44N2O11; 512.29 (M).

[0275] Step 3: Synthesis of (2S)-4-[(2,5,8,ll,14,17,20,23-octaoxapentacosan-25- yl)carbamoyl]-2-{[(prop-2-en-l-yloxy)carbonyl]amino}butanoic acid

[0276] Potassium carbonate (2.14 g ,15 mmol) was added to stirred solution of the product obtained in Step-1 (5.3 g, 10 mmol) in mixture of THF (100 mL) and DM water (100 mL). Reaction mixture was cooled to 0-5 °C. Allyl chloroformate (1.2 mL, 1.11 mmol) was added dropwise to the reaction mixture at 0-5° C. The reaction mixture was allowed to attain RT and then it was stirred at RT overnight for 16h. The reaction mixture was concentrated in vacuo under reduced pressure at 40° C & Tetrahydrofuran was removed. D. M. water (10 mL) was added to the residue, it was cooled to 0-5° Cand acidified up to pH~4 using 2N HC1 solution. It was saturated with sodium chloride and then extracted with ethyl acetate (3xl00mL). Combined organic layer was washed with brine solution (1x20 mb), dried over anhydrous sodium sulphate and concentrated under reduced pressure at 50 °C to get crude product (6.6 gm), which was purified by column chromatography (silica gel 230-400 mesh; DCM: methanol, 90: 10) to get the title compound. LCMS (ESI, m / z): 597.21 [M+H]+; 614.29 [M+H20]+; 619.28 [M+Na]+; 635.17[M+K]+(observed value); Calculated for C26H48N2O13; 596.31(M).

[0277] Step 4: Synthesis of prop-2-en-l-yl N-[(lS)-l-{[(lS)-l-{[(lS)-4- (carbamoylamino)-l-{[4-(hydroxymethyl)phenyl]carbamoyl} butyl] carbarn oyl}- 2-methylpropyl]carbamoyl}-3-[(2,5,8,ll,14,17,20,23-octaoxapentacosan-25- yl)carbamoyl]propyl]carbamate

[0278] DIPEA (0.72 mL, 4.1 mmol) and & TBTU (0.81 g, 2.5 mmol) were sequentially added to a stirred solution of Val-Cit-PAB-OH (0.64 g, 1.6 mmol) (159857-79-1) and the product obtained in Step-3 (1 g, 1.6 mmol) in 10 mL of DMF at RT and the resultant reaction mixture was stirred overnight for 18h at RT. The resultant reaction mixture was diluted with 50 ml diethyl ether. The contents were stirred for 1 hour at RT Precipitates were observed and the contents were allowed to settle. The ethereal layer was decanted off and the residue was impregnated on silica- gel (230-400 mesh) and chromatographed on silica-gel (230-400 mesh) using (12:88) Methanol : DCM as the eluent to obtain title compound. LCMS (ESI, m / z): 958.58 [M+H]+(observed value); Calculated for C44H75N7O16;957.52(M).

[0279] Step 5: Synthesis of (2S)-2-amino-N-[(lS)-l-{[(lS)-4-(carbamoylamino)-l- {[4-(hydroxymethyl)phenyl]carbamoyl}butyl]carbamoyl}-2-methylpropyl]-N'- (2,5,8,ll,14,17,20,23-octaoxapentacosan-25-yl)pentanediamide i.e. Intermediate (I)Intermediate (I)

[0280] Palladium tetrakis(triphenylphosphine) ( 0.06 g, 0.05 mmol) was added to stirred solution of the product obtained in Step-4 (1.35 g, 1.4 mmol) in mixture of DCM (7 mL) and methanol (3 mL) at RT. Morpholine (0.91 mL, 10 mmol) was added to the reaction mixture and stirred for 3 hr. Reaction mixture was concentrated under reduced pressure at 35 °C. Crude material thus obtained was triturated with 30 ml diethyl ether and the ethereal layer was decanted off. The residue was then purified by column chromatography (silica gel 230-400 mesh; DCM: methanol (90: 10) to get title compound i.e. Intermediate (I). LCMS (ESI, m / z): 874.58 [M+H]+(observed value); Calculated for C40H71N7O14 ; 873.50 (M).

[0281] Step 6: Synthesis of (2S)-N-[(lS)-l-{[(lS)-4-(carbamoylamino)-l-{[4 (hydroxymethyl)phenyl] carbamoyl}butyl]carbamoyl}-2-methylpropyl]-2-{l-[3- (2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)propanamido]-3,6,9,12- tetraoxapentadecan-15-amido}-N'-(2,5,8,ll,14,17,20,23-octaoxapentacosan-25- yl)pentanediamideMal-PEG4-NHS-ester

[0282] DIPEA (0.08 mL, 0.44 mmol) was added to a stirred solution of Mal-PEG4- NHS-ester (0.152 g,0.28 mmol) (CAS number 1325208-25-0) and Intermediate (I) (0.2g, 0.2mmol) in DMF and the resultant reaction mixture was stirred at RT for 3 hours. It was concentrated in vacuo at 50 °C under vacuum and the residue was purified by column chromatography (silica gel 230-400 mesh; DCM : methanol : 88: 12 ) to gettitle compound. LCMS (ESI, m / z): 1272.99 [M+H]+, 637.09 [M+2H]2+(observed value); Calculated for C58H97N9O22; 1271.67 (M).

[0283] Step 7: Synthesis of {4-[(2S)-5-(carbamoylamino)-2-[(2S)-2-[(2S)-2-{l-[3- (2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)propanamido]-3,6,9,12- tetraoxapentadecan -15-amido}-4-[(2,5,8,ll,14,17,20,23-octaoxapentacosan-25- yl)carbamoyl] butanamido]-3-methylbutanamido]pentanamido]phenyl} methyl 4-nitrophenyl carbonate (II)

[0284] DIPEA (0.062 mL, 0.363 mmol) followed by bis(4-nitrophenyl) carbonate (0.070 g, 0.232 mmol) were sequentially added to a stirred solution of the product obtained in Step-6 (0.185, 0.145mmol) in DMF (2mL) and the resultant reaction mixture was stirred at RT for 4 hrs. Reaction mixture was then concentrated in vacuo at 47 °C and the residue was triturated with 15 ml diethyl ether & the ethereal layer was decanted off. The residue was dried under vacuum at 40 °C to get Intermediate (II). LCMS (ESI, m / z): 1438.17 [M+H]+, 719.58 [M+2H]2+, 741.57 [M+2Na]2+(observed value); Calculated for CesHiooNioChe; 1436.68 (M).

[0285] Construct C.2:

[0286] DIPEA (0.009 mL, 0.04 mmol) was added to a stirred homogenous mixture of Mal-PEGs-NHS ester (0.028 g, 0.04 mmol; CAS number: 756525-93-6), Intermediate (IV) (0.054, 0.04 mmol; prepared as per the process described below) and DMF (2 mL) at RT. The resultant reaction mixture was stirred at RT for 6 hours and the progress ofreaction was monitored by LCMS. Upon consumption of starting material and formation of product as indicated by LCMS profile, the reaction mixture was concentrated in vacuo at 40 °C. Diethyl ether (15 mL) was added to the residue and the contents were stirred vigorously for 30 minutes upon which precipitates were observed. The resultant contents were allowed to settle and the supernatant liquid was decanted off and the residue dried in vacuo at 40 °C It was purified by reverse flash HPLC with following conditions; column, C18, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.2 as a di-trifluoroacetate salt. LCMS (ESI, m / z): 947.27 [M+2H]2+ / 2; (observed value); Calculated for C87H117N19O29; 1891.82 (M) (free base).

[0287] Preparation of Intermediate (IV): Synthesis of (3E)-7-{ l-[4-({ [({4-[(2S)-2- [(2S)-2-amino-3-methylbutanamido]-3-{[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6- (hydroxymethyl)oxan-2-yl] oxy } propanamido]phenyl } methoxy )carbonyl] amino } amino)-4-oxobutyl] -3 -methyl- lH-pyrazole-5 -amido } -25 -( 1 -ethyl-3-methyl- 1H- pyrazole-5-amido)-14,18-dioxa-l,6,8,24-tetraazapentacyclo [17.6.1.16,9.023,26.013,27]heptacosa-3,7,9,l l,13(27),19,21,23(26),24-nonaene-l l,21- dicarboxamide (IV).

[0288] Step 1 : Synthesis of [(2R,3R,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(2S)-2- ({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-2-{[4-(hydroxymethyl)phenyl] carbamoyl}ethoxy]oxan-2-yl]methyl acetate

[0289] 2-Ethoxy-l -ethoxycarbonyl- 1,2-dihydroquinoline (EEDQ) (0.782 g, 3.16 mmol) was added to a stirred homogenous mixture of (2S)-2-({[(9H-fluoren-9- yl)methoxy]carbonyl}amino)-3-{[(2R,3R,4S,5R,6R)-3,4,5-tris(acetyloxy)-6- [(acetyloxy)methyl]oxan-2-yl]oxy}propanoic acid (1.6 g, 2.43 mmol) (prepared according to procedure published in J. Chem. Soc., Perkin Trans. 1, 1997, 1429- 1442) , 4-aminobenzyl alcohol (0.389 , 3 mmol) and DCM: methanol (7:3) mixture (15mL) at RT. The resultant reaction mixture was stirred at RT for 24 hours overnight. Upon completion of reaction as indicated by thin layer chromatography, the reaction mixture was concentrated on rotavapour in vacuo 40 °C and the crude product obtained was chromatographed on silica-gel (240-400 mesh) using (03 : 97) MeOH : DCM as the eluent to obtain title compound. LCMS (ESI, m / z): 763.18 [M+H]+; 786.50 [M+Na]+(observed value); Calculated for C39H42N2O14; 762.75 (M).

[0290] Step 2. Synthesis of [(2R,3R,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(2S)-2- amino-2-{[4-(hydroxymethyl)phenyl]carbamoyl}ethoxy]oxan-2-yl]methyl acetate

[0291] Triethylamine (1.9 ml, 13.8 mmol) was added to a stirred homogenous solution of the product obtained in Step-1 (1.05 g, 1.38 mmol) in solvent mixture of Tetrahydrofuran : DMF (1: 1) (10 mL) and the resultant reaction mixture was stirred at RT for 17 hours and monitored by T.L.C. Upon completion of reaction, the R.M was concentrated on rotavapour at 50 °C under reduced pressure and the residue was chromatographed by flash chromatography silica-gel (240-400 mesh) using (03 : 97) MeOH : DCM as the eluent to obtain title compound. LCMS (ESI, m / z): 541.37 [M+H]+; (observed value); Calculated for C24H32N2O12 ; 540.51(M).

[0292] Step 3. Synthesis of [(2R,3R,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(2S)-2-{[4- (hydroxymethyl)phenyl]carbamoyl}-2-[(2S)-3-methyl-2-{[(prop-2-en-l- yloxy)carbonyl]amino}butanamido]ethoxy]oxan-2-yl]methyl acetate

[0293] DIPEA (0.37 mL, 2.16 mmol) as well as HATU (0.493 grams, 1.3 mmol) were sequentially added to a stirred homogenous mixture of the product obtained in Step-2 (0.585, 1.08 mmol) and (2S)-3-methyl-2-{[(prop-2-en-l- yloxy)carbonyl]amino}butanoic acid (0.239 g, 1.19 mmol) dissolved in DMF (10 mL) at ambient temperature. The resultant reaction mixture was stirred at RT for 16 hr. Reaction was monitored by thin layer chromatography and upon consumption of starting materials, the reaction mixture was diluted with 100 ml ethylacetate, quenched with 20 ml D.M water and organic and aqueous layers were separated. The organic layer was washed with brine solution (10 mL), dried over anhydrous sodium sulphate and then concentrated in vacuo at 50 °C. The residue was chromatographed on silica- gel (240-400 mesh) using (05 :95) MeOH : DCM as the eluent to obtain title compound. LCMS (ESI, m / z): 746.39 [M+Na]+; (observed value); Calculated for C33H45N3O15; 723.72 (M).

[0294] Step 4. Synthesis of [(2R,3R,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(2S)-2- [(2S)-3-methyl-2-{[(prop-2-en-l-yloxy)carbonyl]amino}butanamido]-2-{[4-({[(4- nitrophenoxy)carbonyl]oxy}methyl)phenyl] carbamoyl}ethoxy]oxan-2-yl]methyl acetate i.e Intermediate (III)

[0295] bis(4-Nitrophenyl)carbonate (0.136 g, 0.45 mmol) was added to a stirred solution DIPEA (0.120 m , 0.7 mmol) and the product obtained in Step-3 (0.2 g, 0.28 mmol) in DMF (5 mL) at ambient temperature and the resultant reaction mixture was stirred at ambient temperature for 4 hours. Reaction progress was monitored by thin layer chromatography and upon consumption of the starting material, the reaction mixture was concentrated in vacuo at 50 °C. The residue was chromatographed on silica-gel (240-400 mesh) as stationary phase and (05:90) MeOH: DCM as the eluent to obtain title compound Intermediate (III). LCMS (ESI, m / z): 911.37 [M+Na]+; (observed value); Calculated for C40H48N4O19; 888.82 (M).

[0296] Step 5. Synthesis of [(2R,3R,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(2S)-2-({4- [({N'-[4-(5-{[(3E)-ll,21-dicarbamoyl-25-(l-ethyl-3-methyl-lH-pyrazole-5- amido)-14,18-dioxa-l,6,8,24-tetraazapentacyclo[17.6.1.16,9.023,26.013,27] heptacosa- 3,7,9,ll,13(27),19,21,23(26),24-nonaen-7-yl]carbamoyl}-3-methyl-lH-pyrazol-l- yl)butanoyl]hydrazinecarbonyl}oxy)methyl] phenyl}carbamoyl)-2-[(2S)-3- methyl-2-{ [(prop-2-en-l-yloxy) carbonyl] amino}butanamido] ethoxy] oxan-2- yl] methyl acetate

[0297] Intermediate III (0.042 g, 0.047 mmol) were sequentially added to a stirred homogenous mixture of DIPEA (0.040 mL, 0.22 mmol), trifluoroacetate salt of P.l (0.05 g, 0.04 mmol) and DMF (3 mL). The resultant reaction mixture was stirred at RT for 6 hours and the reaction progress was monitored by LCMS. After 6 hours diethyl ether (20 mL) was added to above reaction mixture at RT, the contents were stirred vigorously and precipitates were allowed to settle. The supernatant layer was decanted off and the solid precipitated residue was dried in vacuo at 50 °C; LCMS (ESI, m / z): 1592.68 [M+Na]+; (observed value); Calculated for C73H87N17O23 ; 1570.57 (M).

[0298] Step 6. Synthesis of prop-2-en-l-yl N-[(lS)-l-{[(lS)-l-({4-[({N'-[4-(5- {[(3E)-ll,21-dicarbamoyl-25-(l-ethyl-3-methyl-lH-pyrazole-5-amido)-14,18- dioxa-1 ,6,8,24-tetraazapentacyclo [17.6.1.l6,9.023,26.013,27]heptacosa- 3,7,9,ll,13(27),19,21,23(26),24-nonaen-7-yl]carbamoyl}-3-methyl-lH-pyrazol-l- yl)butanoyl]hydrazinecarbonyl}oxy)methyl] phenyl}carbamoyl)-2-{[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] oxy} ethyl] carbarn oyl }-2-m ethylp r opyl] carb am ate

[0299] Water : Triethylamine : Methanol (1:8: 1) mixture (5 mL) was added to a stirred solution of crude material comprising of the product obtained in Step-5 (0.068 g) obtained from step 5 in DMF (1 mL) and the resultant solution was then stirred at ambient temperature for 25-30 hours and the progress of reaction was monitored by LCMS profding. Upon consumption of starting material and formation of product as indicated by LCMS profile, the reaction mixture was concentrated in vacuo at 40 °C. Diethyl ether (15 mL) was added to the residue and the contents were stirred vigorously for 30 minutes upon which precipitates were observed. The resultant contents were allowed to settle and the supernatant liquid was decanted off and the residue dried in vacuo at 40 °C. LCMS (ESI, m / z): 701.85[M+2H]2+; 1403.61[M+H]+; (observed value); Calculated for C65H79N17O19 ; 1402.42 (M).

[0300] Step 7. Synthesis of (3E)-7-{l-[4-({[({4-[(2S)-2-[(2S)-2-amino-3- methylbutanamido] -3- { [(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6- (hydroxymethyl)oxan-2-yl] oxy}propanamido]phenyl}methoxy) carbonyl]amino}amino)-4-oxobutyl]-3-methyl-lH-pyrazole-5-amido}-25-(l- ethyl-3-methyl-lH-pyrazole-5-amido)-14,18-dioxa-l,6,8,24- tetraazapentacyclo[17.6.1.16,9.023,26.013,27]heptacosa- 3,7,9,ll,13(27),19,21,23(26),24-nonaene-ll,21-dicarboxamide (IV)

[0301] Morpholine (0.024 g, 0.3 mmol) and Tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) (0.003 g, 0.0028 mmol) were sequentially added to a stirred homogenous mixture of the crude product obtained in Step-6 (0.060 g), DMF (1 mL) and MeOH: DCM (03:07) (2 mL) at ambient temperature. The resultant reaction mixture was stirred at ambient temperature for 16 hours and progress of reaction was monitored by LCMS profding. Upon consumption of starting material and formation of product as indicated by LCMS profde, the reaction mixture was concentrated in vacuo at 40 °C. Diethyl ether (15 mL) was added to the residue and the contents were stirred vigorously for 30 minutes upon which precipitates were observed. The resultant contents were allowed to settle and the supernatant liquid was decanted off and the residue dried in vacuo at 40 °C to obtain crude light brown solid i.e. Intermediate (IV); LCMS (ESI, m / z): 660.61 [M+2H]2+; 1318.75[M+H]+; (observed value); Calculated for C61H75N17017 ; 1318.35 (M).

[0302] Construct C.3:

[0303] DIPEA (0.042 mL, 0.245 mmol) and HOBt (0.004 g, 0.029 mmol) were sequentially added to a stirred solution of Intermediate (II); (0.088 g, 0.053 mmol) and compound of formula P.4; (0.050 g, 0.040 mmol) in DMF (1.5 mL) at RT and the resultant reaction mixture was then stirred at RT for 6 hrs. The reaction mixture was then diluted with 15 mL diethyl ether and contents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the cruderesidue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, C18, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.3 as a di-trifluoroacetate salt. LCMS (ESI, m / z): 1089.36 [M+2H]2+ / 2; 726.88 [M+3H]3+ / 3 (observed value); Calculated for C100H141N23O32 ; 2176.011 (M) (free base).

[0304] Construct C.4:,[CF3COOH]3

[0305] DIPEA (0.072 mL, 0.09 mmol) and HOBt (0.004 g, catalytic) were sequentially added to a stirred solution of {4-[(2S)-5-(carbamoylamino)-2-[(2S)-2-[(2S)-2-{ l-[3- (2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)propanamido]-3,6,9,12,15,18,21,24- octaoxaheptacosan-27-amido}-4-[(2,5,8,l 1,14, 17,20, 23-octaoxapentacosan-25- yl)carbamoyl]butanamido]-3-methylbutanamido]pentanamido] phenyl}methyl 4- nitrophenyl carbonate Intermediate (V); (0.146 g, 0.09 mmol; (synthesis of Intermediate (V) is described below) and compound of formula P.4 (0.085 g, 0.040 mmol); in DMF (1.5 mL) at RT and the resultant reaction mixture was then stirred at RT for 6 hrs. The reaction mixture was then diluted with 15 mL diethyl ether and contents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the crude residue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, Cl 8, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.4 as a di-trifluoroacetate salt. LCMS (ESI, m / z): 1177.47 [M+2H]2+ / 2; (observed value); Calculated for C108H157N23O36; 2352.11 (M) (free base).

[0306] Preparation of Intermediate (V):

[0307] Synthesis of {4-[(2S)-5-(carbamoylamino)-2-[(2S)-2-[(2S)-2-{l-[3-(2,5- dioxo-2,5-dihydro-lH-pyrrol-l-yl)propanamido]-3,6,9,12,15,18,21,24- octaoxaheptacosan-27-amido}-4-[(2,5,8,ll,14,17,20,23-octaoxapentacosan-25-yl)carbamoyl]butanamido]-3-methylbutanamido]pentanamido] phenyl}methyl 4- nitrophenyl carbonate

[0308] Step 1 : Synthesis of (2S)-N-[(lS)-l-{[(lS)-4-(Carbamoylamino)-l-{[4- (hydroxymethyl)phenyl] carbarn oyl}butyl] carbamoyl}-2-methylpropyl]-2-{l-[3- (2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)propanamido]-3,6,9,12,15,18,21,24- octaoxaheptacosan-27-amido}-N'-(2,5,8,ll,14,17,20,23-octaoxapentacosan-25- yl)pentanediamide

[0309] Solution of Mal-NH-PEG8-CH2CH2C(O)OPFP ester (0.62 g, 0.81 mmol) (CAS No. : 2055023-14-6) in DMF (1 mL) was added to a stirred solution of Intermediate (I) (0.59 g, 0.67 mmol) and DIPEA (0.23 mL, 1.3 mmol) in DMF (1.5 mL). The resultant reaction mixture was stirred at ambient temperature for 4 hours and subsequently concentrated in vacuo at 50 °C. The residue was chromatographed on silica-gel (230-400 mesh) using (12:98) MeOH : DCM to obtain desired product. LCMS (ESI, m / z): , 725.42 [M+2H]2+(observed value); Calculated for C66H113N9O26 ; 1448.94 (M).

[0310] Step 2 : Synthesis of Intermediate (V)

[0311] DIPEA (0.32 mL, 1.8 mmol) followed by Bis(4-nitrophenyl) carbonate (0.56 g, 1.8 mmol) were sequentially added to a stirred solution of (2S)-N-[(lS)-l-{[(lS)-4- (carbamoy lamino) - 1 - { [4-(hydroxymethyl)pheny 1] carbamoyl } butyl] carbamoyl } -2- methylpropyl] -2- { 1 - [3 -(2,5 -dioxo-2, 5 -dihydro- IH-pyrrol- 1 -yl)propanamido] - 3,6,9,12,15,18,21,24-octaoxaheptacosan-27-amido}-N'-(2,5,8,l 1,14,17,20,23- octaoxapentacosan-25-yl)pentanediamide (0.89 g, 0.6 mmol) in DMF (5mL) and the resultant reaction mixture was stirred at RT for 16 hrs. Reaction mixture was then concentrated in vacuo at 47 °C and the residue was triturated with 15 ml diethyl ether & the ethereal layer was decanted off. The residue was dried under vacuum at 40 °C to get Intermediate (V). LCMS (ESI, m / z): 1613.79 [M+H]+, 807.65 [M+2H]2+, (observed value); Calculated for C73H116N10O30 ; 1613.771 (M).

[0312] Construct C.5:

[0313] DIPEA (0.043 mL, 0.25 mmol) was added to a stirred homogenous mixture of 2,5 -dioxopyrrolidin- 1 -yl 1 - [3 -(2,5 -dioxo-2, 5 -dihydro- IH-pyrrol- 1 -yl)propanamido] - 3,6,9,12,15,18,21,24-octaoxaheptacosan-27-oate i.e. Mal-PEGs-NHS ester (0.048 g,0.069 mmol) (CAS : 756525-93-6) , intermediate (VI) (0.079, 0.05 mmol) (obtained in Step 3 as explained below) and DMF (2 mL) at ambient temperature. The resultant reaction mixture was stirred at ambient temperature for 6 hours and the progress of reaction was monitored by LCMS. Upon consumption of starting material and formation of product as indicated by LCMS profile, the reaction mixture was concentrated in vacuo at 40 °C. Diethyl ether (15 mL) was added to the residue and the contents were stirred vigorously for 30 minutes upon which precipitates were observed. The resultant contents were allowed to settle and the supernatant liquid was decanted off and the residue dried in vacuo at 40 °C. It was purified by reverse flash HPLC with following conditions; column, C18, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.5 as a di-trifluoroacetate salt. LCMS (ESI, m / z): 976.34 [M+2H]2+ / 2; (observed value); Calculated for C89H119N19O31 ; 1949.83 (M) (free base).

[0314] Preparation of Intermediate (VI): Synthesis of Tri-trifluoroacetate salt of 2- {N’- [( {4- [(2S)-2- [(2S)-2-amino-3-methylbutanamido] -3- { [(2R,3R,4S,5S,6R)- 3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}propanamido]phenyl} methoxy)carbonyl]-4-(5-{[(3E)-ll,21-dicarbamoyl-25-(l-ethyl-3-methyl-lH- pyrazole-5-amido)-14,18-dioxa-l,6,8,24-tetraazapentacyclo [17.6.1.16,9.023,26.013,27]heptacosa-3,7,9,ll,13(27),19,21,23(26),24-nonaen-7- yl]carbamoyl}-3-methyl-lH-pyrazol-l-yl)butanehydrazido}acetic acid

[0315] Step 1 : Synthesis of 2-[4-(5-{[(3E)-ll,21-dicarbamoyl-25-(l-ethyl-3- methyl-lH-pyrazole-5-amido)-14,18-dioxa-l,6,8,24-tetraazapentacyclo [17.6.1.16,9.023,26.013,27]heptacosa-3,7,9,ll,13(27),19,21,23(26),24-nonaen-7- yl] carbarn oyl}-3-methyl-lH-pyrazol-l-yl)-N'-[({4-[(2S)-2-[(2S)-3-methyl-2-{ [(prop-2-en-l-yloxy)carbonyl] amino}butanamido] -3-{ [(2R,3R,4S,5R,6R)-3,4,5- tris(acetyloxy)-6-[(acetyloxy)methyl] oxan-2-yl]oxy}propanamido] phenyl}methoxy)carbonyl]butanehydrazido]acetic acid

[0316] Intermediate (III) (0.160 g, 0.18 mmol), as synthesized above, was sequentially added to a stirred homogenous mixture of DIPEA (0.179 mL, 1.04 mmol), trifluoroacetate salt of P.4 (0.2 g, 0.16 mmol) and DMF (3 mL). The resultant reaction mixture was stirred at R.T for 6 hours and the reaction progress was monitored by LCMS. After 6 hours diethyl ether (20 mL) was added to above reaction mixture at RT, the contents were stirred vigorously and precipitates were allowed to settle. The supernatant layer was decanted off and the solid precipitated residue was dried in vacuo at 50 °C. LCMS (ESI, m / z): 815.21 [M+2H]2+; 1628.64 [M+H]+(observed value); Calculated for C75H89N17O25 ; 1628.64 (M).

[0317] Step 2. Synthesis of 2-[4-(5-{[(3E)-ll,21-dicarbamoyl-25-(l-ethyl-3- methyl-lH-pyrazole-5-amido)-14,18-dioxa-l,6,8,24-tetraazapentacyclo [17.6.1.16,9.023,26.013,27]heptacosa-3,7,9,ll,13(27),19,21,23(26),24-nonaen-7- yl] carbarn oyl}-3-methyl-lH-pyrazol-l-yl)-N'-[({4-[(2S)-2-[(2S)-3-methyl-2- { [(prop-2-en-l-yloxy)carbonyl] amino}butanamido] -3-{ [(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}propanamido]phenyl} methoxy)carbonyl]butanehydrazido]acetic acid

[0318] Water : Triethylamine : Methanol (1:8: 1) mixture (20 mL) was added to a stirred solution the crude product obtained in Step-1 (0.320 g) in DMF (3 mL) and the resultant reaction mixture was then heated at 60 °C for 12 hours and the progress of reaction was monitored by LCMS profiling. Upon consumption of starting material and formation of product as indicated by LCMS profile, the reaction mixture was concentrated in vacuo at 40 °C. Diethyl ether (15 mL) was added to the residue upon which precipitates were observed and the resultant contents were stirred vigorously for 30 minutes at ambient temperature. Contents were allowed to settle and the supernatant liquid was decanted off and the residue dried in vacuo at 40 °C. LCMS (ESI, m / z): 731.58[M+2H]2+; 1460.55 [M+H]+; (observed value); Calculated for C67H81N17O21 ; 1460.46 (M).

[0319] Step 3. Synthesis of 2-{N'-[({4-[(2S)-2-[(2S)-2-amino-3- methylbutanamido] -3- { [(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6- (hydroxymethyl)oxan-2-yl] oxy} propanamido]phenyl}methoxy)carbonyl]-4-(5- {[(3E)-ll,21-dicarbamoyl-25-(l-ethyl-3-methyl-lH-pyrazole-5-amido)-14,18- dioxa-l,6,8,24-tetraazapentacyclo[17.6.1.16,9.023,26.013,27] heptacosa-3, 7, 9, 11, 13(27), 19, 21, 23 (26),24-nonaen-7-yl]carbamoyl}-3-methyl-lH-pyrazol-l- yl) butanehydrazidojacetic acidINTERMEDIATE (VI)

[0320] Morpholine (0.149 mL, 1.7mmol) and tetrakis(triphenylphosphine)palladinm(0) (Pd(PPh3)4) (0.034 g, 0.03mmol) were sequentially added to a stirred homogenous mixture of crude material obtained in Step 2 (0.254 g), DMF (2 mL) and MeOH: DCM (03:07) (10 mL) at ambient temperature. The resultant reaction mixture was stirred at ambient temperature for 16 hours and progress of reaction was monitored by LCMS profiling. Upon consumption of starting material and formation of product as indicated by LCMS profile, the reaction mixture was concentrated in vacuo at 40 °C. Diethyl ether (15 mL) was added to the residue and the contents were stirred vigorously for 30 minutes upon which precipitates were observed. The resultant contents were allowed to settle, the supernatant liquid was decanted off and the residue dried in vacuo at 40 °C. It was purified by reverse flash HPLC with following conditions; column, Cl 8, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain Intermediate (VI) as a tri-trifluoroacetate salt. LCMS (ESI, m / z): 689.09 [M+2H]2+; 1376.69 [M+H]+; (observed value); Calculated for C63H77N17O19 ; 1375.55 (M) (free base).

[0321] Construct C.6:

[0322] DIPEA (0.018 mL, 0.1 mmol) and HOBt (0.004 g, catalytic) were sequentially added to a stirred solution of Intermediate II ( 0.093 g, 0.060 mmol) and compound of formula (P.8; 0.057 g, 0.05 mmol) in DMF (1.5 mL) at RT and the resultant reaction mixture was then stirred at RT for 24 hrs. The reaction mixture was then diluted with 15 mL diethyl ether and contents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the crude residue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, C18, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.6 as a di -trifluoroacetate salt. LCMS (ESI, m / z): 1184.95 [M+2H]2+ / 2; 790.68 [M+3H]3+ / 3 (observed value); Calculated forC108H158N24O36; 2367.12 (M). (free base).

[0323] Construct C.7:

[0324] DIPEA ( 0.11 mL, 0.6 mmol) and HOBt (0.015 g, catalytic) were sequentially added to a stirred solution of Intermediate (V) ( 0.223 g, 0.138 mmol) and trifluoroacetate salt of compound of formula P.8 ( 0.150 g, 0.1 mmol) in DMF (1.5 mL) at RT and the resultant reaction mixture was then stirred at RT for 24 hrs. The reaction mixture was then diluted with 15 mL diethyl ether and contents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the crude residue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, Cl 8, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.7 as a ditrifluoroacetate salt. LCMS (ESI, m / z): 1273.06 [M+2H]2+ / 2; 849.07 [M+3H]3+ / 3 (observed value); Calculated for C116H174N24O40 ; 2543.23 (M) (free base).

[0325] Construct C.8:,[CF3COOH]3

[0326] A solution of Intermediate (V) ( 0.143 g, 0.088 mmol) and anhydrous HOBt (0.010 g, catalytic) in DMF (2 mL) were sequentially added to a stirred homogenous solution of tri-trifluoroacetate salt of compound of formula P.5 ( 0.099 g, 0.08 mmol) , DIPEA ( 0.083 mL, 0.48 mmol) in DMF (2 mL) at RT and the resultant reaction mixture was then stirred at RT for 7 hours. The reaction mixture was then diluted with 15 mL diethyl ether and contents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the crude residue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, C18, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.8 as a di -trifluoroacetate salt. LCMS (ESI, m / z): 1184.52 [M+2H]2+ / 2 ; 790.37 [M+3H]3+ / 3; Calculated for ; C109H159N23O36; 2366.13 (M) (free base).

[0327] Construct C.9:P.5

[0328] A solution of Intermediate (II) ( 0.115 g, 0.08 mmol) and anhydrous HOBt (0.010 g, catalytic) in DMF (2 mL) were sequentially added to a stirred homogenous solution of tri-trifluoroacetate salt of compound of formula P.5 (0.076 g, 0.06 mmol),DIPEA ( 0.063 mL, 0.36 mmol) in DMF (2 mL) at RT and the resultant reaction mixture was then stirred at RT for 7 hours. The reaction mixture was then diluted with 15 mL diethyl ether and contents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the crude residue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, Cl 8, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.9 as a di-trifluoroacetate salt. LCMS (ESI, m / z): 1096.51 [M+2H]2+ / 2 ; 731.63 [M+3H]3+ / 3; Calculated for C101H143N23O32; 2190.026 (M) (free base).

[0329] Construct C.10:

[0330] A solution of Intermediate (V) (0.177 g, 0.1 mmol) and anhydrous HOBt (0.010 g, catalytic) in DMF (2 mL) were sequentially added to a stirred homogenous solution of compound of formula P.10 ( 0.1 g, 0.1 mmol) , DIPEA ( 0.06 mL, 0.347 mmol) in DMF (2 mL) at RT and the resultant reaction mixture was then stirred at RT for 18 hours. The reaction mixture was then diluted with 15 mL diethyl ether and contents were stirred and allowed to settle where upon precipitates were observed. The ethereal layer was decanted off, the crude residue was dried in vacuo at 30 °C and purified by reverse flash with following conditions; column, Cl 8, mobile phase, water (0.01% TFA) and ACN; with detector UV 254 / 323 nm to obtain compound of formula C.10 as a di-trifluoroacetate salt. LCMS (ESI, m / z): 1237.47 [M+2H]2+ / 2 ; 825.67 [M+3H]3+ / 3; Calculated for ; C113H169N23O39 ; 2472.19 (M) (free base).

[0331] BIOLOGICAL DATA:IRF reporter assay: IRF Reporter (Luc)-THPl Cell line (Cat# 79858, Make: BPS Bioscience) were treated with a concentration range of STING agonists for 24 h with a total of 30,000 cells in each well of a 96-well non-treated U bottom plate. Followingthe incubation, IX Passive lysis buffer from Dual-Luciferase® Reporter Assay System kit (Make: Promega, Cat. No. E1910) was added for 30 min at RT and 40 pl of supernatant was transferred to an opaque 96 well A area plate and incubated with 40 pl of Luciferase Assay Substrate. Luminescence signal was measured immediately using multi-mode microplate reader. ECso values were calculated using non-linear regression analysis of GraphPad Prism. The sting agonists are further categorized as having ECso above or below 100 nM.

[0332] Results for representative compounds are provided in Table 4 below:

[0333] Table 4: ECso of STING agonists in THP1 cell IRF reporter assaya = <10 nM; b = 10-100 nM; c = 100-500 nM

[0334] Preparation of ADCs

[0335] The anti-MUCl-SEA mAb, HM5LM4 (Ref: PCT / IB2024 / 057438) or Trastuzumab, (Ref: Eleftha, Intas Pharmaceuticals, Gujrat India) were buffer exchanged into conjugation buffer (20 mM Sodium Phosphate, 2 mM EDTA, pH 7.4) and inter chain disulfide bond reduction with 8-10 molar excess of TCEP (reducing agent) at 37 °C for -120 minutes. After reduction, it was buffer exchanged through either 30 kDa centrifugal ultrafiltration or by Tangential Flow Filtration (TFF) or Sephadex G25 resin (a gel filtration medium) with conjugation buffer. The thiol concentration of reduced mAb was quantified by Ellman’s reagent, 5,5'-dithiobis (2- nitrobenzoic acid) [DTNB], A 10-20-fold molar excess of respective constructs was added into the reduced antibody (anti-MUCl-SEA mAb or Trastuzumab). The conjugation reaction was carried out in the presence of 5-15 % organic solvent (DMF / DMSO / DMA) and 100 mM sodium caprylate at 22 °C ± 3 °C for 60 minutes. Conjugation reaction was quenched by adding 14-20- fold molar excess of L-cysteine to conjugation reagent. Excess conjugation reagents were removed by buffer exchange process through Sephadex G25 or 30 kDa MWCO filter device. As per requirement, conjugated samples were further purified by HIC (hydrophobic interactionchromatography) or Size Exclusion Chromatography (SEC). Purified ADC(s) were concentrated and buffer exchanged through 30 kDa MWCO centrifugal filter device / TFF system into sodium succinate buffer with 9.0% (w / v) sucrose and 0.04% Tween 80, pH 5.5 and stored either at 2-8°C or -20°C for further use.

[0336] RP-HPLC analysis for DAR evaluation of ADCs

[0337] Conjugated ADC samples were denatured in 8M guanidine-HCl, 50 mM Tris, pH 8 and reduced using 5 mM TCEP. Denatured and reduced samples were heated at 95 °C for about 10 mins. The reduced samples (10 pg) were separated and monitored using UV detection at 280 nm by HPLC with a Bioresolve RP mAb Polyphenyl, 450A, (2.7p, 2.1x100 mm) at the column temperature of 70 °C. The samples were eluted using the mobile phase A (0.1% TFA in water) and mobile phase B (70% ACN, 30% isopropanol and 0.1% TFA) with the flow rate of 0.5 mL / min. Designated peak corresponding to L0, LI, HO, Hl, H2 and H3 were integrated and from the results of integrated peak percentage fragment for light chain and heavy chain, payload distribution and average DAR for ADC was calculated.

[0338] Analysis of purified anti-MUCl-SEA mAb of respective STING agonists demonstrated the purity of >90% monomer as determined by analytical High Performance Size Exclusion Chromatography (HP-SEC). Drug antibody ratio (DAR) assessed by Reverse Phase High Performance Liquid Chromatography (RP-HPLC) demonstrated that the average DAR for purified anti-MUC 1 -SEA STING agonists were found between 1 and 8. Actual DAR values are depicted in table 5.

[0339] Determination of binding ability of ADCs to cancer cell line and determination of ECso of ADCs of STINGag

[0340] Respective anti MUC1 or anti HER2 ADCs of STINGag were added to MUC1 or HER2 expressing cell line such as COLO-357 or SKOV3 at a concentration range of 0-70 nM respectively. The cells were maintained at 4 °C for 1 hour and washed with the excess cell culture media. These cells were further stained with goat anti-human IgG, Fey, conjugated with Alexa Fluor 647 for 30 min at 4 °C. The concentration for goat anti-human IgG, Fey was used as per manufacturer’s instructions. The cells were washed with the excess cell culture media and re-suspended in 100 pl of cell culture media. Cell-associated fluorescence was detected and recorded using flow cytometry (Beckman Coulter, Cytoflex). The data were further analyzed using Flow Jo software todetermine the mean fluorescence intensity (MFI). The MFI values obtained from FlowJo were plotted against concentration using GraphPad Prism. A non-linear regression model was applied to the resulting curve to calculate the ECso value.

[0341] ECso values (in nM) for ADC binding to COLO-357 and SKOV3 cell lines are provided in table 5.

[0342] Binding ability of various STINGag ADC were found to be comparable to that of the non-conjugated mAb

[0343] Determination of Equilibrium dissociation constant (KD) using Surface Plasmon Resonance (SPR) for various STINGag ADCs for binding to their respective target proteins

[0344] Recombinant target protein such as MUC1-SEA antigen (Acrobiosystems, Cat: MU1-H52H9) orHER2 antigen (Acrobiosystem cat: HE2-H52H9-100ug) was captured on CM5 chips covalently immobilized with anti -His mAb at 5 pl / min flow rate for 60s. Various concentrations of ADCs (0-50 nM) were passed over captured target antigens at a flow rate of 30 pl / min flow rate for 120s, keeping dissociation time of 1800s at 25°C. The dose response generated was evaluated using the 1: 1 fit model on Biaevaluation software for the calculation of KD (Refer table 5).

[0345] Binding ability of various STINGag ADCs were found to be comparable to that of the non-conjugated mAb.

[0346] ADC induced PBMC-mediated cytotoxicity against respective target expressing cancer cell lines for various STINGag ADCs

[0347] Human pancreatic adenocarcinoma cell line (COLO-357) or human breast cancer line (SKOV3) were seeded in separate 48 well plate in RPMI-1640 medium with 10% FBS and allowed to adhere for 4 to 6 hours. Various concentrations of ADCs of STINGag (0 -500 nM of equivalent payload on ADCs) were then added to each well and the plate was incubated for 20 to 60 min at 37 °C. PBMCs isolated from healthy donors were then added to each well in PBMC: cancer cell line ratio of 8 : 1 and incubated for 4-7 days. Each well was washed thrice with PBS (IX) to remove the non-adherent PBMCs and the viability of cancer cell line was measured using viability reagents (Prestoblue from Thermo Fisher Scientific or CellTiter-Glo from Promega as per manufacturer’s instruction). ECso values were derived from dose-response curves generated by plotting the concentration of equivalent payload in ADCs against thepercent viability of cancer cell lines, relative to untreated controls (Table 5). Cytotoxic effects were observed for both anti-MUCl-SEA-STINGag ADC and Trastuzumab- STINGag ADC.

[0348] Table 5: DAR, cytotoxicity, KD value and Cell viability data for ADCs of present disclosureFoot note: 1) In equivalent to payload

[0349] ADC induced tumor growth inhibition and / or regression at 3 mg / kg dose in COLO-357 ectopic tumor-bearing nude mice for anti-MUCl-SEA-STINGag ADC (STINGag of HM5LM4)

[0350] COLO-357 cells mixed with matrigel were inoculated subcutaneously by injecting 100 pL containing approximately 1 x 106cells in the flank region of mice in an aseptic environment. Tumor size measurements were initiated post 7 days of cell inoculation and monitored two times per week throughout the study. Mice were randomized into different treatment groups (n= 8-9 / group) such that each treatment arm had similar mean tumor volumes — 180 mm3and standard error of mean (S.E.M.). Mice were injected with respective ADC with dose regimens as, 3 doses (i.v., q7d x 3). Mice were monitored for changes in tumor volume, body weight and clinical signs twice a week. Tumor volume at the subcutaneously implanted site was estimated by measuring the length and width of the tumor using a digital Vernier caliper. Normal saline was used as vehicle. Data summarized in Table 6.

[0351] Table 6: Tumor Growth Inhibition of ADCs of the present disclosure

[0352] All the ADC tested above showed anti-tumor efficacy in COLO-357 cancer cell line. ADC2 HM5LM4-MUC-82 showed tumor growth inhibition of 61% and other ADCs showed tumor regression ranging from 86- 96% on day 29. None of the ADCs showed significant weight loss during the study period.

Claims

Claims:

1. A compound of F ormula I :or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-NH-R4, -NR5R6, -O-C1-6 alkyl-O-Ci-6 alkyl-CON(R7)-NH-R8and -CO-NR9R10; whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -C1-4 alkyl, -Ci-e alkyl-COOH, -C3-6 cycloalkyl-COOH, -C1-6 alkyl-CONRnR12, -Ci-6-alkyl-NR13R14, and -Ci-ealkyl-OR15;R5is -Ci-e alkyl-COOH;R6is -Ci-6 alkyl-CONHNH2;R7is selected from hydrogen and -Ci-6-alkyl;R8is selected from hydrogen and -Ci-6-alkyl;R9is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R10is selected from -(CH2)I-6NH-CH2-(CHOH)I-6-CH2OH, -(CH2)I-6NH-CH2-(CHOH)I-6- COOH, -(CH2)I-6NH-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH, and -Ci-6-alkyl-COOH;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl and R17is hydrogen or -C1-3 alkyl.

2. The compound of Formula I as claimed in claim 1, whereinR1is selected from -NH2and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-NH-R4, -NR5R6, -O-C1-6 alkyl-O-Ci-6 alkyl-CON(R7)-NH-R8and -CO-NR9R10; whereinR3is selected from hydrogen and -Ci-3-alkyl;R4is selected from hydrogen, -Ci-3-alkyl, -C1-6 alkyl-COOH, -Ci-6 alkyl-CONRnR12, -C1-6- alkyl-NR13R14, and -C1-6 alkyl-OR15;R5is -C 1-6 alkyl-COOH;R6is -Ci-6 alkyl-CONHNH2;R7is hydrogen;R8is hydrogen;R9is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R10is selected from -(CH2)I-3NH-CH2-(CHOH)I-6-CH2OH, -(CH2)I-3NH-CH2-(CHOH)I-6- COOH, -(CH2)I-3NH-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH, and -C 1-3 -alkyl-COOH;R11is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I- 6-CH2O-(CH2)I-3-COOH and -Ci-3-alkyl-COOH;R13is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

3. The compound of Formula I as claimed in claim 1, whereinR1is -NH2;R2is -CON(R3)-NH-R4, whereinR3is hydrogen;R4is selected from hydrogen, methyl, -C1-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, -Ci-3-alkyl- NR13R14, and -Ci-3 alkyl-OR15;R11is selected from hydrogen, -Ci-2-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)4-CH2OH and -CH2-(CHOH)4-COOH and -CH2- (CHOH)4-CH2O-(CH2)-COOH;R13is -C 1-3 -alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is C1-3 alkylene.

4. The compound of Formula I as claimed in claim 1, whereinR1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is selected from hydrogen, methyl, -C1-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, -Ci-3-alkyl- NR13R14, and -Ci-3 alkyl-OR15;R11is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;R13is -C 1-3 -alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH;Y is -CH2-; andZ is C1-4 alkylene.

5. The compound of Formula I as claimed in claim 1, whereinR1is -NH2;R2is -CO-NR9R10; whereinR9is hydrogen;R10is -(CH2)2-3NH-CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ; andZ is ethylene, which is unsubstituted.

6. The compound of Formula I as claimed in claim 1, whereinR1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is -CH2COOH;Y is -(CH2)m, wherein m is 1 ; andZ is propylene, which is unsubstituted.

7. The compound of Formula I as claimed in claim 1, whereinR1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is -(CH2)2COOH;Y is -(CH2)m, wherein m is 1 ; andZ is propylene, which is unsubstituted.

8. The compound of Formula I as claimed in claim 1, whereinR1is -NH2;R2is -CON(R3)-NH-R4; whereinR3is hydrogen;R4is -(CH2)2-CONRnR12;R11is methyl;R12is -CH2-(CHOH)4-CH2OHY is -(CH2)m, wherein m is 1 ; andZ is propylene, which is unsubstituted.

9. A compound of Formula la:Formula-la pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof; wherein:R3is selected from hydrogen, and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH, -C3-6 cycloalkyl-COOH, -C1-6 alkyl-CONRnR12, -Ci-6-alkyl-NR13R14, and -Ci-ealkyl-OR15;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

10. The compound of Formula la as claimed in claim 9, whereinR3is hydrogen;R4is selected from hydrogen, -Ci-4-alkyl, -C1-6 alkyl-COOH, -Ci-6 alkyl-CONRnR12-Ci-6- alkyl-NR13R14, and -C1-6 alkyl-OR15;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH and -CH2-(CHOH)4- CH2O-(CH2)-COOH;R13is selected from -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is -CH2-(CHOH)I-6-COOH; andZ is C1-6 alkylene, which is unsubstituted.

11. The compound of Formula la as claimed in claim 9, whereinR3is hydrogen;R4is selected from hydrogen, -Ci-2-alkyl, -C1-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, -C1-3- alkyl-NR13R14, and -C1-3 alkyl-OR15;R11is selected from hydrogen, -Ci-2-alkyl and -C2-3-alkyl-COOH;R12is selected from -CH2-(CHOH)4-CH2OH, -CH2-(CHOH)4-COOH and -CH2-(CHOH)4- CH2O-(CH2)-COOH;R13is -C 1-3 -alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH; andZ is C1-3 alkylene, which is unsubstituted.

12. The compound of Formula la as claimed in claim 9, whereinR3is hydrogen;R4is selected from hydrogen, -Ci-2-alkyl, -C2-3 alkyl-COOH, -C1-3 alkyl-CONRnR12, -C2-3- alkyl-NR13R14, and -C2-3 alkyl-OR15;R11is selected from hydrogen, methyl and -C2-3-alkyl-COOH;R12is -CH2-(CHOH)4-CH2OH;R13is -C 1-3 -alkyl-COOH;R14is -CH2-(CHOH)4-CH2OH;R15is -CH2-(CHOH)2-COOH; andZ is C2-3 alkylene, which is unsubstituted.

13. The compound of Formula la as claimed in claim 9, whereinR3is hydrogen;R4is -C1-3 alkyl-COOH; andZ is propylene, which is unsubstituted.

14. A compound of Formula lb,or pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof; wherein p is an integer between 1-6;R3is selected from hydrogen and -Ci-4-alkyl;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen and -NR16R17, wherein R16is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl.

15. The compound of Formula lb as claimed in claim 14, whereinR11is selected from hydrogen, -Ci-2-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)4-CH2OH, -CH2-(CHOH)4-COOH, -CH2-(CHOH)4-CH2O- (CH2)-COOH and -CH2-(CHOH)4-CH2O-(CH2)-COOH; andZ is Ci-3 alkylene, which is unsubstituted.

16. The compound of Formula I as claimed in claim 1 to claim 15, wherein the compound selected from the following:or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof.

17. The compound of Formula I as claimed in claim 1 to claim 15, wherein the compound is selected from the following:

18. The compound of Formula I as claimed in claim 1 to claim 15, wherein the compound is selected from the following:

19. A pharmaceutical composition comprising a compound of Formula I, Formula la or Formula lb as claimed in claim 1 to claim 18 and pharmaceutically acceptable excipient.

20. A method of treating disease or disorder mediated by STING in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of Formula I, Formula la or Formula lb as claimed in claim 1 to claim 18 or a pharmaceutically acceptable salt thereof.

21. Use of the compound of Formula I, Formula la or Formula lb as claimed in claim 1 to claim 18 or a pharmaceutically acceptable salt thereof for the treatment of diseases or disorders mediated by STING.

22. Use of the compound of Formula I, Formula la or Formula lb as claimed in claim 1 to claim 18 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating a disease or disorder mediated by STING.

23. Use of the compound of Formula I, Formula la or Formula lb as claimed in claim 1 to claim 18 or a pharmaceutically acceptable salt thereof for the treatment of diseases or disorders mediated by STING, wherein the STING mediated disease or disorder is selected from inflammation, allergic diseases, autoimmune diseases, infectious diseases, cancer, pre- cancerous syndromes, sickle cell disease, sickle cell anaemia, systemic lupus erythematosus (SUE), cutaneous lupus, lupus nephritis, psoriasis, diabetes mellitus including insulindependent diabetes mellitus (IDDM), dermatomyositis, systemic sclerosis (scleroderma), and Sjogren's syndrome (SS), rheumatoid arthritis, psoriatic arthritis, STING associated vasculitis with onset at infancy (SAVI), Aicardi Goutieres syndrome (AGS), chilblain lupus, and mixed connective tissue disease.

24. Use of the compound of Formula I, Formula la or Formula lb as claimed in claim 23, wherein the cancer is selected from myelodysplastic syndrome, melanoma, germ cell tumors, gastrointestinal stromal tumor (GIST), non-small cell lung carcinoma (NSCLC), mastocytosis, neuroblastoma, glioblastoma, astrocytoma, hepatocellular carcinoma, renal cell cancer, breast cancer, cutaneous systemic sclerosis, prostate and colorectal cancer, brain cancer, bladder cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, head and neck cancer, liver cancer, lung cancer, lymphoma, ovarian cancer, pancreatic cancer, renal cancer, skin cancer, stomach cancer, testis cancer, thyroid cancer, and urothelial cancer and other solid tumors.

25. A construct of Formula C-I or Formula C-II:Formula C-I Formula C-II and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula I as claimed in claim 1 with a linker of Formula[-Q-A-L or , whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)-, -NR5R6, -O-C1-4 alkyl-O-Ci-4 alkyl- CON(R7)-N(R8)- and -CO-NR9R10-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, C3-6-cycloalkyl-COOH, -C1-6- alkyl-CONRnR12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -Ci-ealkyl-COOH;R6is -Ci-ealkyl-CONHNH-;R7' is selected from hydrogen and -Ci-6 alkyl;R8' is selected from hydrogen and -Ci-6 alkyl;R9' is selected from hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6-COOH)- and - (CH2)I-6N(-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl, and R17is hydrogen or -C1-3 alkyl;Q is selected from following moieties:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q with L-4 at position #;A is a natural or non-natural amino acid or a peptide of 2 to 5 amino acids, wherein A is attached to Q through its C terminal; andL is selected from following moieties:wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

26. The construct of Formula C-I or Formula C-II as claimed in claim 25, wherein A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly- Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective e-acid derivatives,ORA is a peptide selected from following moieties:wherein w is an integer selected from 1 to 24.

27. The construct of Formula C-I or Formula C-II as claimed in claim 25, wherein Q is Moiety Q- 1 and A is peptide selected from Moiety A-2, wherein w is an integer selected from 1 to 24, and Moiety A-4.

28. The construct of Formula C-I or Formula C-II as claimed in claim 25, whereinQ is Moiety Q-l;A is a peptide selected from Moiety A-2 wherein w is an integer selected from 1 to 24, and Moiety A-4; andL is Moiety L-2, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

29. The construct of Formula C-I and C-II as claimed in claim 25, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CONR9R10;R3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, -Ci-6-alkyl-CONRnR12';R9is selected from hydrogen, -Ci-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6-COOH)- and - (CH2)I-6N(-CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, Ci-3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl; and R17' is hydrogen or -C1-3 alkyl;Q is selected from Moiety Q-l, Moiety Q-2 and Moiety Q-3; wherein ‘]’ denotes attachment of Q to R2; and ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q to L-4 at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly- Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val, which is unsubstituted or substituted with -C1-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective C5 or Ce- acid derivatives,ORA is a peptide selected from Moiety A-l, Moiety A-2 wherein w is an integer selected from 1 to 24, Moiety A-3, Moiety A -4, Moiety A-5 and Moiety A-6; wherein A is attached to Q through its C terminal; andL is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

30. The construct of Formula C-I or Formula C-II as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NH-R4, whereinR3’ is hydrogen;R4is selected from hydrogen, -Ci-3-alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONRnR12';R11' is hydrogen, -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -CH2-;Z is straight Ci-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l, Moiety Q-2 and Moiety Q-3, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q to L at position #;A is a peptide selected from Moiety A-l, Moiety A-2 wherein w is an integer selected from 1 to 24, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6; wherein A is attached to Q through its C terminal; andL is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4, wherein s is an integer selected from 1-4 and t is an integer selected from 4-18.

31. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is selected from -CON(R3)-NR4- and -CO-NR9R10-; whereinR3is hydrogen;R4is selected from hydrogen, -C1-3 alkyl-COOH and -C1-3 alkyl-CONR11R12';R9' is hydrogen;R10' is-(CH2)i-6N(-CH2-(CHOH)i-6-CH2OH)-;R11is selected from hydrogen and -Ci-6-alkyl;R12is -CH2-(CHOH)I-6-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is C1-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l, Moiety Q-2 and Moiety Q-3, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L, while ‘)’ denotes the attachment of Q to L at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly- Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce- acid derivatives,ORA is a peptide selected from Moiety A-l, Moiety A-2 wherein w is an integer selected from 1 to 24, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6; wherein A is attached to Q through its C terminal; andL is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

32. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is selected from -CON(R3)-NR4- and -CO-NR9R10-; whereinR3is hydrogen;R4is selected from hydrogen, -Ci-e alkyl-COOH and -Ci-6 alkyl-CONRnR12';R9is hydrogen;R10' is-(CH2)i-6N(-CH2-(CHOH)i-6-CH2OH)-;R11is selected from hydrogen and -Ci-3-alkyl;R12is -CH2-(CHOH)I-4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is Ci-3 alkylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is peptide selected from Moiety A-2 wherein w is an integer selected from 4 to 18 and Moiety A-4; andL is Moiety L-2, wherein s is an integer selected from 1-3 and t is an integer selected from 4-33. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A -2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

34. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4' is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

35. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

36. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

37. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

38. The construct of Formula C-I as claimed in claim 25, whereinR1is -NFL;R2is -CON(R3)-NR4-, whereinR3is hydrogen;R4is -(CH2)2-CONRnR12’; whereinR11’ is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

39. The construct of Formula C-I as claimed in claim 25, whereinR1is -NFL;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-CONR11R12’;R11’ is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

40. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

41. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.\T142. The construct of Formula C-I as claimed in claim 25, whereinR1is -NH2;R2is -CONR9R10-; whereinR9' is hydrogen;R10' is -(CH2)2N(-CH2-(CHOH)4-CH2OH)-;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; Wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

43. A construct of Formula C-Ia:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula la as in claim 1 with a linker of Formula [-Q-A-L, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH, -C3-6 cycloalkyl-COOH, -C1-6 alkyl-CONR11R12, -Ci-6-alkyl-NR1,3R’14’, and -Ci-e alkyl-OR15’;R11is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I- 6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH; andZ is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, Ci-3 alkoxy, halogen or -NR16'R17', wherein R16is hydrogen or -C1.3 alkyl, and R17is hydrogen or -C1.3 alkyl;Q is selected from following moieties:wherein denotes attachment of Q to A;A is a natural or non-natural amino acid or a peptide of 2 to 5 amino acids, wherein A is attached to Q through its C terminal; andL is selected from following moietieswherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

44. The construct of Formula C-Ia as claimed in claim 43, whereinR3is hydrogen;R4is selected from hydrogen, -Ci-6 alkyl-COOH and -Ci-e alkyl-CONR11R12;R11is selected from hydrogen and -Ci-6-alkyl;R12is -CH2-(CHOH)I-6-CH2OH; and Z is Ci-6 alkylene, which is unsubstituted;Q is Moiety Q-l, whereindenotes attachment of Q to A;A is a peptide selected from following moieties:o e y - yMoiety A-4 wherein w is an integer selected from 1 to 24, andL is Moiety L-2, wherein s is an integer selected from 2-4 and t is an integer selected from 2-4.

45. The construct of Formula C-Ia as claimed in claim 43, whereinR3is hydrogen;R4is selected from hydrogen, methyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONR11R12;R11is selected from hydrogen, -Ci-3-alkyl and -Ci-3-alkyl-COOH;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH; and Z is C1-6 alkylene, which is unsubstituted.

46. The construct of Formula C-Ia as claimed in claim 43, wherein Q is Moiety Q-l.

47. The construct of Formula C-Ia as claimed in claim 43, wherein Q is Moiety Q-l and A is peptide selected from Moiety A-2, wherein w is an integer selected from 1 to 24, and Moiety A-4.

48. The construct of Formula C-Ia as claimed in claim 43, wherein Q is Moiety Q-l; A is peptide selected from Moiety A-2 wherein w is an integer selected from 1 to 24, and MoietyA-4; and L is Moiety L-2, wherein s is an integer selected from 1-10 and t is an integer selected from 1-24.

49. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4' is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

50. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4' is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

51. The construct of Formula C-I as claimed in claim 43, whereinR1is -NIL;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

52. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CHQCOOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

53. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-4; andL is Moiety L-2, wherein s is 2 and t is 8.

54. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-CONR11R12’;R11’ is methyl;R12is CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

55. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-CONR11R12;R11’ is methyl;R12is CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

56. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 8.

57. The construct of Formula C-I as claimed in claim 43, whereinR1is -NH2;R2is -CON(R3)-NR4-; whereinR3is hydrogen;R4is -(CH2)2-COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q-l; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is Moiety A-2, wherein w is 8; andL is Moiety L-2, wherein s is 2 and t is 4.

58. An antibody-drug conjugate of Formula A:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the compound of Formula I as claimed in claim 1 to an antibody via a linker U, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)-, -NR5R6-, -O-C1-4 alkyl-O-Ci-4 alkyl- CON(R7)- N(R8)- and -CO-NR9R10-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, C3-6-cycloalkyl-COOH, -C1-6- alkyl-CONR11R12', -Ci-6-alkyl-NR13R14'and -Ci-6-alkyl-OR15';R5is -Ci-ealkyl-COOH;R6is -Ci-ealkyl-CONHNH-;R7' is selected from hydrogen and -C1-6 alkyl;R8is selected from hydrogen and -C1-6 alkyl;R9' is selected from hydrogen, -C1-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6N(-CH2-(CHOH)I-6-COOH)- and - (CH2)I-6N(CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH ;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4; andZ is straight or branched Ci-6 alkylene which is unsubstituted or substituted with hydroxy, Ci- 3 alkoxy, halogen or -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

59. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is selected from -NH2and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CONR9R10;R3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH and -Ci-6-alkyl-CONRnR12' ;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CH2)m, wherein m is 1 to 4;Z is straight or branched C1-6 alkylene, which is unsubstituted or substituted with hydroxy, - C1-3 alkoxy, halogen and -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

60. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-NR4-;R3is hydrogen;R4is selected from hydrogen, -C1-3 alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONRnR12';R11is selected from hydrogen and -Ci-3-alkyl;R12is selected from -CH2-(CHOH)4-CH2OH and -CH2-(CHOH)4-COOH;Y is -CH2-;Z is straight C1-6 alkylene, which is unsubstituted;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

61. The antibody drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-NR4-;R3is hydrogen;R4is selected from hydrogen, methyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONRnR12';Rn' is selected from hydrogen, -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -CH2-;Z is C1-6 alkylene, which is unsubstituted;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

62. The antibody drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is selected from -CON(R3)-NR4- and -CO-NR9R10; whereinR3is hydrogen;R4is selected from hydrogen, -C1-3 alkyl-COOH and -C1-3 alkyl-CONR11R12';R9' is hydrogen;R10' is -(CH2)I-6N(-CH2-(CHOH)I-6-CH2OH)-;R11is hydrogen;R12is -CH2-(CHOH)I-4-CH2OH;Y is -(CFbjm, wherein m is 1 ;Z is straight or branched Ci-6 alkylene, which is unsubstituted;Ab is an antibody; andU is a linker moiety connecting compound of Formula I to the antibody.

63. The antibody-drug conjugate of Formula A as claimed in claim 58, wherein the compound of Formula I is selected from the following:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, wherein ‘*’ represents point of attachment to U.

64. The antibody-drug conjugate of Formula A as claimed in claim 58 to claim 63, wherein U is linker moiety with following structure:AI[-Q-A-L1- or, wherein Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L', while ‘)’ denotes the attachment of Q to L' at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly- Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce- acid derivatives,ORA is a peptide selected from following moieties:Moiety A- 1 Moiety A-2 Moiety A-3wherein w is an integer selected from 1-24 and A is atached to Q through its C terminal;L' is a moiety selected from:Moiety L'-4 wherein ‘**’ is atachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24.

65. The antibody-drug conjugate of Formula A as claimed in claim 58 to claim 63, wherein the Ab is an antibody binding to MUC1, EGFR, HER2, HER3, MUC16, TROP2, Nectin-4, 5T4, PSMA, CD19, CD22, CD33, CD37, CD38, CD40, CD44, CD52, CD79b, GPR20, FAP, cMET or GRP78.

66. The antibody-drug conjugate of Formula A as claimed in claim 58 to claim 63, wherein the Ab is an antibody binding to MUC1-SEA domain or HER2.

67. The antibody-drug conjugate of Formula A as claimed in claim 58 to claim 63, wherein the antibody is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

68. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is selected from -NFE and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CONR9R10;R3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH and -Ci-6-alkyl-CONRnR12,;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CH2)m, wherein m is 1 to 4;Z is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen and -NR16R17', wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;U is a linker moiety connecting compound of Formula I to the antibody; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

69. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4' is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

70. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4' is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

71. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is CFECOOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

72. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8;Ab is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

73. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NIL;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CIL)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

74. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

75. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

76. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1 is -NH2;R2’ is -CON(R3)-N(R4)-, whereinR3' is hydrogen;R4' is -CH2CH2COOH;Y is -(CFhjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

77. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1 is -NH2;R2’ is -CON(R3')-N(R4')-, whereinR3' is hydrogen;R4' is -CH2CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

78. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NIL;R2is -CO-NR9R10-, whereinR9' is hydrogen;R10' is -(CH2)2 N(-CH2-(CHOH)4-CH2OH)-;Y is -(CIL)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

79. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NIL;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is hydrogen;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

80. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CFbjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is trastuzumab.

81. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CFbjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

82. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CFbjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

83. The antibody-drug conjugate of Formula A as claimed in claim 58, whereinR1is -NH2;R2is -CON(R3)-N(R4)-, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Y is -(CFbjm, wherein m is 1 ;Z is propylene, which is unsubstituted;U is linker moiety [-Q-A-L1-, whereinQ is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

84. An antibody-drug conjugate of Formula A-I or Formula A -II:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the construct of Formula C-I or Formula C-II, respectively as claimed in claim 25 with a linker of Formula[-Q-A-L’ or , whereinR1is -NH2 and -NH-Ci-6-alkyl;R2is -CON(R3)-N(R4)-, -NR5R6-, -O-Ci-4 alkyl-O-Ci-4 alkyl-CON(R7)-N(R8)- and -CO- NR9R10-, whereinR3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH, C3-6-cycloalkyl-COOH, -C1-6- alkyl-CONRnR12', -Ci-6-alkyl-NR13R14' and -Ci-6-alkyl-OR15';R5is -Ci-ealkyl-COOH;R6is -Ci-ealkyl-CONHNH-;R7' is selected from hydrogen and -C1-6 alkyl;R8is selected from hydrogen and -C1-6 alkyl;R9' is selected from hydrogen, -C1-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6-N(-CH2-(CHOH)I-6-CH2OH)-, -(CH2)I-6-N(-CH2-(CHOH)I-6-COOH)-, and -(CH2)I-6-N(CH2-(CHOH)I-6-CH2O-(CH2)I-3-COOH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH,-CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Y is -(CH2)m, wherein m is 1 to 4;Z is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen or -NR16'R17', wherein R16' is hydrogen or -C1-3 alkyl, and R17' is hydrogen or -C1-3 alkyl;Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L1, while ‘)’ denotes the attachment of Q to L1at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly- Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -C1-6alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce- acid derivatives,ORA is a peptide selected from following moieties:Moiety A-4 wherein w is an integer selected from 1-24 and A is attached to Q through its C terminal;L' is a moiety selected from:wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24; andAb is an antibody.

85. The antibody-drug conjugate of Formula A-I as claimed in claim 84, whereinR1is selected from -NH2 and -NH-Ci-6-alkyl;R2is selected from -CON(R3)-N(R4)- and -CON(R9R10)R3is selected from hydrogen and -Ci-6-alkyl;R4is selected from hydrogen, -Ci-6-alkyl, -Ci-6-alkyl-COOH and -Ci-6-alkyl-CONRnR12';R9is selected from hydrogen, -C1-6 alkyl and -Ci-6-alkyl-COOH;R10' is -(CH2)I-6-N(-CH2-(CHOH)I-6-CH2OH)-;R11is selected from hydrogen, -Ci-4-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -CH2-(CHOH)I-6- CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;Y is -(CFhjm, wherein m is 1 to 4;Z is straight or branched C1-6 alkylene, which is unsubstituted or substituted with hydroxy, - C1-3 alkoxy, halogen or -NR16R17' wherein R16' is hydrogen or -C1-3 alkyl and R17' is hydrogen or -C1-3 alkyl;Q is selected from Moiety Q-l and Moiety Q-2, wherein ‘]’ denotes attachment of Q toR2; while ‘}’ denotes attachment of Q to A;A is a peptide selected from Moiety A-l, Moiety A -2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 and A is attached to Q through its C terminal;L1is selected from Moiety L-l, Moiety L-2, Moiety L-3 and Moiety L-4; wherein s is an integer selected from 2-4 and t is an integer selected from 4-18; andAb is an antibody.

86. The antibody-drug conjugate of Formula A-I as claimed in claim 84, whereinR1is -NH2;R2is -CON(R3)-NR4-, whereinR3is hydrogen;R4is selected from hydrogen, -Ci-3-alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONR11R12';R11is selected from hydrogen and -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -(CH2)m, wherein m is 1 ;Z is straight or branched C1-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is a peptide selected from Moiety A-l, Moiety A -2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 w and A is attached to Q through its C terminal;L1is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is an antibody.

87. The antibody-drug conjugate of Formula A-I as claimed in claim 84, whereinR1is -NH2;R2is -CON(R3)-NR4-, whereinR3is hydrogen;R4is selected from hydrogen, -Ci-3-alkyl, -C1-3 alkyl-COOH and -C1-3 alkyl-CONR11R12';R11is selected from hydrogen and -Ci-3-alkyl;R12is selected from -CH2-(CHOH)I-4-CH2OH and -CH2-(CHOH)I-4-COOH;Y is -(CH2)m, wherein m is 1 ;Z is straight or branched C1-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2, wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A;A is a peptide selected from Moiety A-l, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 w and A is attached to Q through its C terminal;L' is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is a humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

88. An antibody-drug conjugate of Formula A-Ia:and pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, tautomer or deuterated analog thereof, formed by conjugating the construct of Formula C-Ia as claimed in claim 43, wherein R3is selected from hydrogen and -Ci-4-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH, -C3-6 cycloalkyl-COOH, -C1-6 alkyl-CONR11R12', -Ci-6-alkyl-NR13R14' and -C1-6 alkyl-OR15';Rnis selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R12is selected from -CH2-(CHOH)I-6-CH2OH, -CH2-(CHOH)I-6-COOH, -(CH2)I-6NH-CH2- (CHOH)I-6-CH2O-(CH2)I-3-COOH and -Ci-6-alkyl-COOH;R13’ is selected from hydrogen, -Ci-6-alkyl and -Ci-6-alkyl-COOH;R14' is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;R15is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Z is straight or branched Ci-6 alkylene, which is unsubstituted or substituted with hydroxy, - Ci-3 alkoxy, halogen or -NR16R17, wherein R16is hydrogen or -C1-3 alkyl and R17is hydrogen or -C1-3 alkyl;Q is a moiety selected from:wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L', while ‘)’ denotes the attachment of Q to L' at position #;A is a peptide selected from Ala-Ala, Ala-Ala-Ala, Ala-Phe, Vai-Ala, Val-Cit, Ala-Val-Cit, Ala(beta)-Val-Cit, Glu-Val-Cit, Vai-Ser, Glu-Cit, Glu-Val, Gly-Gly, Gly-Gly-Phe, Gly-Gly- Phe-Gly, Asp-Cit, Asp-Val-Cit and Asp-Val which is unsubstituted or substituted with -Ci-6 alkyl, polyhydroxy alkyl, glucopyranose moieties, pentose, hexose, their respective Cs or Ce- acid derivatives,ORA is a peptide selected from following moieties:Moiety A-5an^ Moiety A-6Moiety A-4 wherein w is an integer selected from 1-24 and A is attached to Q through its C terminal; andL' is selected fromMoiety L'-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-10 and t is an integer selected from 1-24; andAb is an antibody.

89. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is selected from hydrogen and -Ci-4-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH and -Ci-6 alkyl-CONR11R12';Rn' is selected from hydrogen and -Ci-6-alkyl;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Z is Ci-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L';A is a peptide selected from Moiety A-l, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 w and A is attached to Q through its C terminal;L' is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is an antibody.

90. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is selected from hydrogen and -Ci-4-alkyl;R4is selected from hydrogen, -Ci-4-alkyl, -Ci-6 alkyl-COOH and -Ci-6 alkyl-CONR11R12';Rn' is selected from hydrogen and -Ci-6-alkyl;R12is selected from -CH2-(CHOH)I-6-CH2OH and -CH2-(CHOH)I-6-COOH;Z is Ci-6 alkylene, which is unsubstituted;Q is selected from Moiety Q-l and Moiety Q-2; wherein ‘]’ denotes attachment of Q to R2; while ‘}’ denotes attachment of Q to A or L';A is a peptide selected from Moiety A-l, Moiety A-2, Moiety A-3, Moiety A-4, Moiety A-5 and Moiety A-6, wherein w is an integer between 4-18 w and A is attached to Q through its C terminal; andL' is selected from Moiety L’-l, Moiety L’-2, Moiety L’-3 and Moiety L’-4 wherein ‘**’ is attachment site to the antibody, s is an integer selected from 1-4 and t is an integer selected from 4-18; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

91. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, wherein Q is Moiety Q- 1.

92. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, wherein Q is Moiety Q-l and A is peptide selected from Moiety A-2, wherein w is an integer between 1-24 and Moiety A-4.

93. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, wherein Q is Moiety Q-l; A is peptide selected from Moiety A-2 and Moiety A-4 and L’ is Moiety L’-2.

94. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, wherein the Ab is an antibody binding to MUC1, EGFR, HER2, HERB, MUC16, TROP2, Nectin-4, 5T4, PSMA, CD19, CD22, CD33, CD37, CD38, CD40, CD44, CD52, CD79b, GPR20, FAP, cMET or GRP78.

95. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, wherein the Ab is an antibody binding to MUC1-SEA domain or HER2.

96. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, wherein the antibody is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

97. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is hydrogen;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

98. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4' is hydrogen;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

99. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

100. The antibody-drug conjugate of Formula A-Ia as claimed in claims 88, wherein R3is hydrogen;R4is -CH2COOH;Y is -(CH2)m, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

101. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -CH2COOH;Y is -(CFEjm, wherein m is 1 ;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

102. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

103. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

104. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3' is hydrogen;R4is -CH2CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8; andL’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

105. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3' is hydrogen;R4is -CH2CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is humanized monoclonal antibody which binds to the MUC1-SEA domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

106. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4' is hydrogen;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8; andAb is trastuzumab.

107. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 4; andAb is trastuzumab.

108. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8;Ab is trastuzumab.

109. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -CH2COOH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-4;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8;Ab is trastuzumab.

110. The antibody-drug conjugate of Formula A-Ia as claimed in claim 88, whereinR3is hydrogen;R4is -Ci-6-alkyl-CONRnR12';R11is methyl;R12is -CH2-(CHOH)4-CH2OH;Z is propylene, which is unsubstituted;Q is Moiety Q 1 ;A is a peptide Moiety-2, wherein w is integer 8;L’ is Moiety L’-2, wherein s is integer 2 and t is integer 8;Ab is trastuzumab.

111. A pharmaceutical composition comprising an antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia as claimed in claim 58 to claim 110 and pharmaceutically acceptable excipient.

112. A method of treating disease or disorder mediated by STING in a subject comprising administering to the subject a therapeutically effective amount of the antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia as claimed in Claim 58 to claim 110.

113. Use of an antibody drug conjugate of Formula A, Formula A-I, Formula A-II or Formula A-Ia as claimed in claim 58 to claim 110, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a disease or disorder mediated by STING.

114. Use of an antibody drug conjugate of Formula-A, Formula A-I, Formula A-II or Formula A-Ia as claimed in claim 58 to claim 110, or a pharmaceutically acceptable salt thereof, for treating a disease or disorder mediated by STING.

115. Use of an antibody drug conjugate of Formula-A, Formula A-I, Formula A-II or Formula A-Ia as claimed in claim 114, wherein the disease or disorder mediated by STING is selected from inflammation, allergic diseases, autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes, sickle cell disease, sickle cell anaemia, systemic lupus erythematosus (SUE), cutaneous lupus, lupus nephritis, psoriasis, diabetes mellitus including insulin-dependent diabetes mellitus (IDDM), dermatomyositis, systemic sclerosis (scleroderma), and Sjogren's syndrome (SS), rheumatoid arthritis, psoriatic arthritis, STING associated vasculitis with onset at infancy (SA VI), Aicardi Goutieres syndrome (AGS), chilblain lupus, and mixed connective tissue disease.

116. Use of an antibody drug conjugate of Formula-A, Formula A-I, Formula A-II or Formula A-Ia as claimed in claim 115, wherein the cancer is selected from myelodysplastic syndrome, melanoma, germ cell tumors, gastrointestinal stromal tumor (GIST), non-small cell lung carcinoma (NSCEC), mastocytosis, neuroblastoma, glioblastoma, astrocytoma, hepatocellular carcinoma, renal cell cancer, breast cancer, cutaneous systemic sclerosis, prostate and colorectal cancer, brain cancer, bladder cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, head and neck cancer, liver cancer, lungcancer, lymphoma, ovarian cancer, pancreatic cancer, renal cancer, skin cancer, stomach cancer, testis cancer, thyroid cancer, and urothelial cancer and other solid tumors.

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