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1. (WO2018122419) INHIBITEURS DE TRANSGLUTAMINASES
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

Claims

A compound of the general formula (I):


wherein

n is an integer selected from 1 , 2 or 3;

W represents


R2 represents -H, -R1, -OR1, -NH2, -NH(R1), -NH(OR1), -N(R1)(R3);

R1 and R3 represent independently of each other -CH3, -CH2CH3, — CH2CH2CH3, — CH(CH3)2, — CH2CH2CH2CH3, — CH2CH2CH2CH2CH3, — CH2CH2CH2CH2CH2CH3, — CH2CH2CH2CH2CH2CH2CH3, — CH2CH(CH3)2, — CH(CH3)CH2CH3, — CH(C2H5)2, — CH2CH(C2H5)2, — C(CH3)3, — CH2— C(CH3)3, -cyclo-C3H5, -cyclo-C4H7, -cyclo-C5H9, -cyclo-C6H11, -CH2-cyclo-C3H5, -CH2-cyclo-C4H7, -CH2-cyclo-C5H9, -CH2-cyclo-C6H11, -Ph, -CH2-Ph, — CH2OCH3, — CH2OCH2CH3, — CH2CH2OCH3, — CH2CH2OCH2CH3, -CH2CO2CH3, -CH2CO2CH2CH3, -CH2CH2NHCH3, -CH2CH2N(CH3)2, -CH2S(O)2-(4-methyl-phenyl),

ZN represents EN— , EN— ASN1— , EN— ASN2— ASN1— , EN-ASN3-ASN2-ASN1- or EN-ASN4-ASN3-ASN2-ASN1-

Zc represents -Ec, -ASC1-EC, -ASC1-ASC2-EC, -ASC1-ASC2-ASC3-EC, -ASC1-ASC2-ASC3-ASC4-EC, -ASC1-ASC2-ASC3-ASC4-ASC5-EC, -ASC1-ASC2-ASC3-ASC4-ASC5-ASC6-EC,

-ASC1-ASC2-ASC3-ASC4-ASC5-ASC6-ASC7-EC,

-ASC1-ASC2-ASC3-ASC4-ASC5-ASC6-ASC7-ASC8-EC,

AS - AS and AS - AS are independently of each other selected from the group consisting of:

Ec is selected from C terminal groups consisting of: -OR8, -NR9R10,

-NHSO2R11 , -O-L1-R8, -O-L1-O-R8, -NH-L1-O-R8, -NH-L1-NRV0, -NHSOz-L1-R11 ,

EN is selected from N terminal groups consisting of: -H, -COCF3,

-CH3, -C2H5, -C3H7, -CH(CH3)2, -CH(C2H5)2, -C4Hg, -C5H11, -C6H13,

— CH2— CH(CH3)2, — CH2— CH(C2H5)2, — CH(CH3)— C2H5, — C(CH3)3, — CH2— C(CH3)3, -cyclo-C3H5, -cyclo-C4H7, -cyclo-C5H9, -cyclo-C6H11, -CH2-cyclo-C3H5, -CH2-cyclo-C4H7, -CH2-cyclo-C5H9, -CH2-cyclo-C6H11, -Ph, -CH2-Ph,

-CH2F, -CHF2, -CF3, -CH2CI, -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, — CH2— CF3, — CH2— CH2CI, — CH2— CH2Br, — CH2— CH2I, — CH2— CH=CH2, -CH2-C≡CH, -CHO, -COCH3, -COC2H5, -COC3H7, -COCH(CH3)2, -COCH(C2H5)2, -COC4H9, -COC5H11, -COC6H13, -COCH2-CH(CH3)2, -COCH2-CH(C2H5)2, -COCH(CH3)-C2H5, -COC(CH3)3, -COCH2-C(CH3)3,

-CO-cyclo-C3H5, -CO-cyclo-C4H7, -CO-cyclo-C5H9, -CO-cyclo-C6H11, -COCH2-cyclo-C3H5, -COCH2-cyclo-C4H7, -COCH2-cyclo-C5H9, -COCH2- cyclo-C6H11, -COPh, -COCH2-Ph, -COOCH3, -COOC2H5, -COOC3H7, -COOCH(CH3)2, -COOCH(C2H5)2, -COOC4H9, -COOC5H11, -COOC6H13, -COOCH2-CH(CH3)2, -COOCH2-CH(C2H5)2, -COOCH(CH3)-C2H5,

-COOC(CH3)3, -COOCH2-C(CH3)3, -COO-cyclo-C3H5, -COO-cyclo-C4H7, -COO-cyclo-C5H9, -COO-cyclo-C6H11, -COOCH2-cyclo-C3H5, -COOCH2-cyclo- C4H7, -COOCH2-cyclo-C5H9, -COOCH2-cyclo-C6H11, -COOPh, -COOCH2-Ph,

with proviso that when ZN is EN and Zc is Ec, then Ec is not -OR8 and/or EN is not -H,

R4, R5 and R6 represent independently of each other: -H, -F, -CI, -Br, -I, -CH3, -CH2CH3, -CH(CH3)2, -cyclo-C3H5, -OCH3, -OCH2CH3, -OCH(CH3)2, -O-cyclo-C3H5, -CF3, -CF2CF3, -OCHF2, -OCF3, -OCF2CF3, -OH, -CN, -CHO, -COCH3, -COCH2CH3, -COCH(CH3)2, -COCH2F, -COCH2CI, -COCF3, -COCCI3, -CO2H, -CO2H, -CO2Me, -CO2CH2CH3, -CO2CH(CH3)2,

-OCOCH3, -OCOCH2CH3, -OCOCH(CH3)2, -OCOCF3, -OCOCCI3, -NH2, -NHCH3, -N(CH3)2, -NHCH2CH3, -NHCH(CH3)2, -N(CH2CH3)2, -NH-cyclo- C3H5, -NHCOCH3, -NHCOCF3, -NHSO2CH3, -NHSO2CF3, -SCH3, -SCH2CH3, -SCH(CH3)2, -S-cyclo-C3H5, -SOCH3, -SOCF3, -SO2CH3, -SO2CF3, -SO2NH2, -SO2NHCH3, -SO2N(CH3)2, -SO2NHCH2CH3,

-SO2NHCH(CH3)2, -SO2NH-cyclo-C3H5, -SO2N(CH2CH3)2, or

R4 and R5 or R5 and R6 form together the following five or six rings:

R7 represents -H, -CH2CO2H, -CH2CH2CO2H, -CH2CH2CH2CO2H,

-CH2CONH2, -CH2CH2CONH2, or -CH2NHCONH2;

R8, R9, R10 and R11 represent independently of each other: -H, -CH3, -CH2CH3, -CH2CH2CH3, _CH(CH3)2, — CH(C2H5)2, -CH2CH(CH3)2, — CH2— CH(C2H5)2,

— C4Hg, — C5H-11, — C6Hi3, — CH(CH3)— C2H5, — C(CH3)3, — CH2— C(CH3)3,


R12 - R29 represents independently of each other -H, -F, -CI, -Br, -I, -OH,

-CN, -NO2, -CH3, -C2H5, -C3H7, -CH(CH3)2, -C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -cyclo-C3H5, -CH2-cyclo-C3H5, -CH2F, -CHF2, -CF3, -CH2CI, -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, -CH2-CF3, -CH2-CH2CI, -CH2-CH2Br, -CH2-CH2I, -OCH3, -OC2H5, -OC3H7, -OCH(CH3)2, -OC(CH3)3, -OC4H9, -OCHF2, -OCF3, -OCH2CF3, -OC2F5,

-OCH2OCH3, -O-cyclo-C3H5, -OCH2-cyclo-C3H5, -O-C2H4-cyclo-C3H5, -CHO, -COCH3, -COCF3, -COC2H5, -COC3H7, -COCH(CH3)2, -COC(CH3)3,

-COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH(CH3)2, -COOC(CH3)3,

-OOC-CH3, -OOC-CF3, -OOC-C2H5, -OOC-C3H7, -OOC-CH(CH3)2, -OOC-C(CH3)3, -NH2, -NHCH3, -NHC2H5, -NHC3H7, -NHCH(CH3)2, -NHC(CH3)3, -N(CH3)2, -N(C2H5)2, -N(C3H7)2, -N[CH(CH3)2]2, -N[C(CH3)3]2, -NHCOCH3, -NHCOCF3, -NHCOC2H5, -NHCOC3H7, -NHCOCH(CH3)2,

-NHCOC(CH3)3, -CONH2, -CONHCH3, -CONHC2H5, -CONHC3H7, -CONHCH(CH3)2, -CONH-cyclo-C3H5, -CONHC(CH3)3, -CON(CH3)2, -CON(C2H5)2, -CON(C3H7)2, -CON[CH(CH3)2]2, -CON[C(CH3)3]2, -SO2NH2, -SO2NHCH3, -SO2NHC2H5, -SO2NHC3H7, -SO2NHCH(CH3)2, -SO2NH-cyclo-C3H5, -SO2NHC(CH3)3, -SO2N(CH3)2, -SO2N(C2H5)2,

-SO2N(C3H7)2, -SO2N[CH(CH3)2]2, -SO2N[C(CH3)3]2, -NHSO2CH3,

-NHSO2CF3, -NHSO2C2H5, -NHSO2C3H7, -NHSO2CH(CH3)2,

-NHSO2C(CH3)3, -CH=CH2, -CH2-CH=CH2, -C(CH3)=CH2, -CH=CH-CH3, -C≡CH, -C≡C-CH3, -CH2-C≡CH, -Ph, -O-Ph, or -O-CH2-Ph,

or R12 and R13, R13 and R14, R24 and R25, R25 and R26, R27 and R28, R28 and R29 can form together the following five or six rings, when R12-R14, R24-R29 are substiuted at six-membered ring;

RN, represents independently of each other -H, -CH3, -C2H5, -C3H7, -CH(CH3)2, -C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -cyclo-C3H5, -CH2-cyclo-C3H5, -CH2F, -CHF2, -CF3, -CH2CI, -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, -CH2-CF3, -CH2-CH2CI, -CH2-CH2Br, -CH2-CH2I,

-CH2-CH=CH2, -CH2-C≡CH, -CHO, -COCH3, -COC2H5, -COC3H7, -COCH(CH3)2, -COC(CH3)3, -COOCH3, -COOC2H5, -COOC3H7, -COOCH(CH3)2, -COOC(CH3)3,

R - R represent independently of each other -H, -CH3, -C2H5, -C3H7, -CH(CH3)2, -C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -cyclo-C3H5,

-CH2-cyclo-C3H5, -CH2F, -CHF2, -CF3, -CH2CI, -CH2Br, -CH2I, — CH2— CH2F, — CH2— CHF2, — CH2— CF3, — CH2— CH2CI, — CH2— CH2Br, — CH2— CH2I, -CH2-CH=CH2, -CH2-C≡CH, -CH2Ph, -CHO, -COCH3, -COC2H5, -COC3H7, -COCH(CH3)2, -COC(CH3)3, -COOCH3, -COOC2H5, -COOC3H7, -COOCH(CH3)2, -COOC(CH3)3, or -COOCH2Ph;

L1 - L8 represent independently of each other a covalent bond, -CH(CH3)-, -CH(CH3)2- -CO-, -SO-, -SO2-

L9 and L10 are independently of each other: a covalent bond, -CH2- -CH2CH^, -CO-, -CH2CO-, -COCH2-, -CO-CH=CH-, -COO-, -O-CO-,

-CH2CO2-, -CO2CH2-, -CONH-, -NHCO-, -CH2CONH-, -CONHCH2-, -CSNH-, -NHCS-, -SO2-, -SO2CH2-, -SO2NH-, or -SO2NHCH2-;

or diastereomer, enantiomer, mixture of diastereomers, mixture of enantiomer, racemates, prodrugs, solvates, hydrates, or pharmaceutically acceptable salts thereof.

The compound according to Claim 1 having any one of the formulae (II-1 ) - (II-5)


wherein

ZC2 represents -Ec, -ASC3-EC, -ASC3-ASC4-EC, -ASC3-ASC4-ASC5-EC, -ASC3-ASC4-ASC5-ASC6-EC, -ASC3-ASC4-ASC5-ASC6-ASC7-EC, or

-ASC3-ASC4-ASC5-ASC6-ASC7-ASC8-EC;

ZN represents EN— , EN— ASN1— , EN— ASN2— ASN1— , EN-ASN3-ASN2-ASN1-, or EN-ASN4-ASN3-ASN2-ASN1- ;

preferred, ZN is EN-, or EN-ASN1-; and

Ec, EN, n, ASC3- ASC8, ASN1 - ASN4, and W have the same meanings as defined in Claim 1 .

3. The compound according to Claim 1 or 2 having any one of the formulae (II1-1 ) - (III-5):


(III-5)

wherein

ZC3 represents -Ec, -ASC4-EC, -ASC4-ASC5-EC, -ASC4-ASC5-ASC6-EC,

-ASC4-ASC5-ASC6-ASC7-EC, or -ASC4-ASC5-ASC6-ASC7-ASC8-EC;

ZN represents EN— , EN— ASN1— , EN— ASN2— ASN1— , EN-ASN3-ASN2-ASN1- ; or EN-ASN4-ASN3-ASN2-ASN1- ; and

Ec, EN, n, ASC4- ASC8, ASN1 - ASN4, and W have the same meanings as defined in Claim 1 .

4. The compound according to any one of Claims 1 to 3 having any one of the formulae (VI-1 ) - (VI-5):

wherein

ZN represents EN- or EN— ASN1— ,

ZC3 represents -Ec, -ASC4-EC, -ASC4-ASC5-EC, -ASC4-ASC5-ASC6-EC;

R2 represents-OCH3, -NH2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH2CH2CH2CH3, -NHCH2CH2CH2CH2CH3, -NH-cyclo-C3H5, or -NHCH2Ph ; and

ASC4 - ASC6, ASN1, Ec, and EN have the same meanings as defined in Claim 1 ,

The Compound according to Claims 1 or 2 having any one of the formulae (VII-3) -

wherein

R2 represents -OCH3, -NH2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH2CH2CH2CH3, -NHCH2CH2CH2CH2CH3, -NH-cyclo-C3H5, or -NHCH2Ph; and

ZN1 represents EN- or EN— ASN2— ,

ZC2 represents -Ec, -ASC3-EC, -ASC3-ASC4-EC, -ASC3-ASC4-ASC5-EC, or -ASC3-ASC4-ASC5-ASC6-EC;

ASC3 - ASC6, ASN2, Ec, and EN have the same meanings as defined in Claim 1 ,

Compounds of the formula (IX):


wherein

ZC1 represents -Ec, or -ASC2-EC;

ASC2, Ec, R4 - R7, W and ZN have the same meaning as defined in Claim 1

The compound according to Claim 6 having the formula (XI-3):

wherein

ZC1 represents -Ec;

ZN represents EN— or EN— ASN1 ;

R2 represents -CH3, -CH2CH3, -CH(CH3)2, -cyclo-C3H5, -Ph

-OCH3, -OCH2CH3, -NH2, -NHCH3, -N(CH3)2

-NH-cyclo-C3H5, -NH-CH2Ph, -NC(CH3)3, -NH-CgHn, -NHCH2OCH3

-NHCH2CH2OCH3, -NHCH2CO2OCH3, -NH-OCH2-cyclo-C5H9, ; and

R4, R5 and R6 represent independently of each other: -H, -F, -CI, -Br, -I

-CH3, -CH2CH3, -CH(CH3)2, -cyclo-C3H5, -OCH3, -CF3, -OCF3, -OH, -CN

-COCH3, -CO2H, -CO2Me, -OCOCH3, -NH2, -NHCH3, -N(CH3)2

-NHCOCH3, -NHCOCF3, -NHSO2CH3, -NHSO2CF3, -SCH3, -SO2CH3

-SO2CF3, -SO2NH2, -SO2NHCH3, or -SO2N(CH3)2.

R7 represents -H or -CH2CH2CO2H; and

ASN1, Ec, and EN have the same meanings as defined in Claim 1 .

The compound according to claim 1 having the formula (XIII);


wherein

n is an integer selected from 1 , 2 or 3;

W represents


R2 represents -H, -R1, -OR1, -NH2, -NH(R1), -N(R1)(R3);

R1 and R3 represent independently of each other -CH3, -CH2CH3, — CH2CH2CH3, — CH(CH3)2, — CH2CH2CH2CH3, — CH2CH2CH2CH2CH3, — CH2CH2CH2CH2CH2CH3, — CH2CH2CH2CH2CH2CH2CH3, — CH2CH(CH3)2, — CH(CH3)CH2CH3, — CH(C2H5)2, — CH2CH(C2H5)2, — C(CH3)3, — CH2— C(CH3)3, -cyclo-C3H5, -cyclo-C4H7, -cyclo-C5H9, -cyclo-C6H11, -CH2-cyclo-C3H5, -CH2-cyclo-C4H7, -CH2-cyclo-C5H9, -CH2-cyclo-C6H11, -Ph, -CH2-Ph, — CH2OCH3, — CH2OCH2CH3, — CH2CH2OCH3, — CH2CH2OCH2CH3, -CH2CO2CH3, -CH2CO2CH2CH3, -CH2CH2NHCH3, -CH2CH2N(CH3)2, -CH2S(O)2-(4-methyl-phenyl),

R19 - R20 represents independently of each other -H, -F, -CI, -Br, -I, -OH, -CN, -NO2, -CH3, -C2H5, -C3H7, -CH(CH3)2, -C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -cyclo-C3H5, -CH2-cyclo-C3H5, -CH2F, -CHF2, -CF3, -CH2CI, -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, -CH2-CF3, -CH2-CH2CI, -CH2-CH2Br, -CH2-CH2I, -OCH3, -OC2H5, -OC3H7, -OCH(CH3)2, -OC(CH3)3, -OC4H9, -OCHF2, -OCF3, -OCH2CF3, -OC2F5, -OCH2OCH3,

-O-cyclo-C3H5, -OCH2-cyclo-C3H5, -O-C2H4-cyclo-C3H5, -CHO, -COCH3, -COCF3J -COC2H5, -COC3H7J -COCH(CH3)2J -COC(CH3)3J -COOH, -COOCH3, -COOC2H5, -COOC3H7J -COOCH(CH3)2J -COOC(CH3)3, -OOC-CH3, -OOC-CF3J -OOC-C2H5, -OOC-C3H7J -OOC-CH(CH3)2, -OOC-C(CH3)3, -N H2J -NHCH3J -NHC2H5, -NHC3H7, -NHCH(CH3)2, -NHC(CH3)3, -N(CH3)2, -N(C2H5)2, -N(C3H7)2J -N[CH(CH3)2]2J -N[C(CH3)3]2, -NHCOCH3, -NHCOCF3, -NHCOC2H5, -NHCOC3H7J -NHCOCH(CH3)2, -NHCOC(CH3)3, -CON H2, -CONHCH3J -CONHC2H5, -CONHC3H7, -CONHCH(CH3)2, -CONH-cyclo-C3H5, -CONHC(CH3)3J -CON(CH3)2J -CON(C2H5)2, -CON(C3H7)2, -CON[CH(CH3)2]2, -CON[C(CH3)3]2J -SO2N H2J -SO2NHCH3, -SO2NHC2H5, -SO2NHC3H7, -SO2NHCH(CH3)2J -SO2NH-cyclo-C3H5, -SO2NHC(CH3)3, -SO2N(CH3)2, -SO2N(C2H5)2, -SO2N(C3H7)2J -SO2N[CH(CH3)2]2, -SO2N[C(CH3)3]2, -NHSO2CH3, -NHSO2CF3J -NHSO2C2H5, -NHSO2C3H7, -NHSO2CH(CH3)2, -NHSO2C(CH3)3, -CH=CH2J -CH2-CH=CH2J -C(CH3)=CH2, -CH=CH-CH3, -C≡CH, -C≡C-CH3, and -CH2-C≡CH;

EN is selected from N terminal groups consisting of:

— H , — COCH3, — COCF3, — CH3, — C2H5, — C3H7, — CH(CH3)2, — C4Hg, -CH2-CH(CH3)2J -CH(CH3)-C2H5, -C(CH3)3, -cyclo-C3H5, -CH2-cyclo-C3H5, -CH2F, -CHF2J -CF3J -CH2CI , -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, — CH2— CF3, — CH2— CH2CI , — CH2— CH2Br, — CH2— CH2I, — CH2— CH=CH2, — CH2-C=CH, -CHO, -COCH3J -COC2H5, -COC3H7, -COCH(CH3)2, -COC(CH3)3, -COOCH3,

RN, represents independently of each other -H, -CH3, -C2H5, -C3H7, -CH(CH3)2, -C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -cyclo-C3H5,

-CH2-cyclo-C3H5, -CH2F, -CHF2, -CF3, -CH2CI, -CH2Br, -CH2I, -CH2-CH2F, — CH2— CHF2, — CH2— CF3, — CH2— CH2CI, — CH2— CH2Br, — CH2— CH2I,— CH2— CH=CH2, -CH2-C≡CH, -CHO, -COCH3, -COC2H5, -COC3H7, -COCH(CH3)2, -COC(CH3)3, -COOCH3, -COOC2H5, -COOC3H7, -COOCH(CH3)2, -COOC(CH3)3,

R27 - R29 represents independently of each other

-H, -F, -CI, -Br, -I, -OH, -CN, -NO2, -CH3, -C2H5, -C3H7, -CH(CH3)2,

-C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -cyclo-C3H5, -CH2-cyclo-C3H5, -CH2F, -CHF2, -CF3, -CH2CI, -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, -CH2-CF3, -CH2-CH2CI, -CH2-CH2Br, -CH2-CH2I, -OCH3, -OC2H5, -OC3H7, -OCH(CH3)2, -OC(CH3)3, -OC4H9, -OCHF2, -OCF3, -OCH2CF3, -OC2F5, -OCH2OCH3, -O-cyclo-C3H5, -OCH2-cyclo-C3H5, -O-C2H4-cyclo-C3H5, -CHO,

-COCH3, -COCF3, -COC2H5, -COC3H7, -COCH(CH3)2, -COC(CH3)3, -COOH, -COOCH3, -COOC2H5, -COOC3H7, -COOCH(CH3)2, -COOC(CH3)3, -OOC-CH3, -OOC-CF3, -OOC-C2H5, -OOC-C3H7, -OOC-CH(CH3)2, -OOC-C(CH3)3, -NH2, -NHCH3, -NHC2H5, -NHC3H7, -NHCH(CH3)2, -NHC(CH3)3, -N(CH3)2, -N(C2H5)2, -N(C3H7)2, -N[CH(CH3)2]2, -N[C(CH3)3]2,

-NHCOCH3, -NHCOCF3, -NHCOC2H5, -NHCOC3H7, -NHCOCH(CH3)2, -NHCOC(CH3)3, -CONH2, -CONHCH3, -CONHC2H5, -CONHC3H7, -CONHCH(CH3)2, -CONH-cyclo-C3H5, -CONHC(CH3)3, -CON(CH3)2,

-CON(C2H5)2, -CON(C3H7)2, -CON[CH(CH3)2]2, -CON[C(CH3)3]2, -SO2NH2, -SO2NHCH3, -SO2NHC2H5, -SO2NHC3H7, -SO2NHCH(CH3)2,

-SO2NH-cyclo-C3H5, -SO2NHC(CH3)3, -SO2N(CH3)2, -SO2N(C2H5)2, -SO2N(C3H7)2, -SO2N[CH(CH3)2]2, -SO2N[C(CH3)3]2, -NHSO2CH3,

-NHSO2CF3, -NHSO2C2H5, -NHSO2C3H7, -NHSO2CH(CH3)2,

-NHSO2C(CH3)3, -CH=CH2, -CH2-CH=CH2, -C(CH3)=CH2, -CH=CH-CH3, -C≡CH, -C≡C-CH3, -CH2-C≡CH, -Ph, -O-Ph, or -O-CH2-Ph,

or R24 and R25, R25 and R26, R27 and R28, R28 and R29 can form together the following five or six rings, when R2 -R29 are substituted at six-membered ring;


9. The compound according to Claim 8 having the fomula (XIV-1 )

wherein

n, W, EN and R27 - R29 have the same meanings as defined Claim 8.

10. Compound according to claim 1 selected from the group consisting of:

(S)-methyl 2-((S)-1 -((S)-2-((S)-2-acetamido-6-amino-5,6-dioxohexanamido)-3- methylbutanoyl)pyrrolidine-2-carboxamido)-4-methylpentanoate (E01 ),

(S)-methyl 2-((S)-1 -((S)-2-((S)-6-amino-2-(benzyloxycarbonylamino)-5,6- dioxohexanamido)-3-methylbutanoyl)pyrrolidine-2-carboxamido)-4- methylpentanoate (E02),

(S)-2-acetamido-N1 -((S)-5-amino-1 -((2S,3R)-1 -((S)-1 -amino-3-methyl-1 -oxobutan- 2-ylamino)-3-methyl-1 -oxopentan-2-ylamino)-1 ,5-dioxopentan-2-yl)-5- oxohexanediamide (E03),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-(1 -methyl-1 H-imidazole-5-carboxannido)-5-oxohexanediannide (E04),

(S)-2-(2-bromo-4-methylthiazole-5-carboxamido)-N1 -(1 -(2-(isopentylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-oxohexanediannide (E05),

(S)-5-acetamido-6-(4-(2-chlorophenyl)piperazin-1 -yl)-2,6-dioxohexanamide (E06),

(S)-1 -acetyl-N-((S)-6-amino-1 -(4-(3-methylpyridin-2-yl)piperazin-1 -yl)-1 ,5,6-trioxohexan-2-yl)pyrrolidine-2-carboxannide (E07),

(S)-1 -((S)-2-((S)-1 -((4R.7S.10S,13S,16S)-7-(4-amino-3,4-dioxobutyl)-10,13-dibutyl-4-(carboxymethyl)-18-methyl-2,5,8,1 1 ,14-pentaoxo-3,6,9,12,15-pentaazanonadecanecarbonyl)pyrrolidine-2-carboxamido)-3-(1 H-indol-3-yl)propanoyl)pyrrolidine-2-carboxylic acid (E08),

(S)-N1 -((S)-1 -((R)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)piperidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-yl)-2-(6-hydroxy-5-nitronicotinamido)-5-oxohexanediannide (E09),

3-((2S)-6-amino-1 -((2S)-3-cyclopropyl-1 -((1 R,2S)-2-((2S)-1 -((2S)-2-(1 -(2,6-dimethylphenoxy)propan-2-ylcarbamoyl)-2-methylpyrrolidin-1 -yl)-1 -oxopentan-2-ylcarbamoyl)-6,6-dinnethyl-3-azabicyclo[3.1 .0]hexan-3-yl)-1 -oxopropan-2-ylamino)-1 ,5,6-trioxohexan-2-ylcarbannoyl)-5-nitrobenzoic acid (E10),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-oxo- 2-(pyrazine-2-carboxamido)hexanediannide (E11 ),

(S)-2-benzamido-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-oxohexanediannide (E12),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-(2-methyl-5-nitrobenzannido)-5-oxohexanediannide (E13),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-(4-methylthiazole-5-carboxannido)-5-oxohexanediannide (E14),

(S)-2-(5-(dimethylannino)naphthalene-1 -sulfonamido)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-oxohexanediannide (E15),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxannido)-5-oxohexanediannide (E16),

(S)-N1 -ethyl-N6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-(1 -methyl-1 H-imidazole-5-carboxamido)-2-oxohexanediamide (E17),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-(1 -methyl-1 H-imidazole-5-carboxannido)-5-oxo-N6-pentylhexanediannide (E18),

(S)-N1 -cyclopropyl-N6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-(1 -methyl-1 H-imidazole-5-carboxamido)-2-oxohexanediamide (E19),

(S)-N1 -benzyl-N6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin- 3- yl)-5-(1 -methyl-1 H-imidazole-5-carboxamido)-2-oxohexanediamide (E20),

(S)-N1 -tert-butyl-N6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-(1 -methyl-1 H-imidazole-5-carboxamido)-2-oxohexanediamide (E21 ),

(S)-2-((S)-1 -acetylpyrrolidine-2-carboxamido)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-oxo-N6-pentylhexanediamide (E22),

(S)-2-benzamido-N6-cyclopropyl-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-oxohexanediamide (E23),

(S)-methyl 2-((S)-1 -((S)-2-((S)-2-benzamido-6-(cyclopropylamino)-5,6-dioxohexanamido)-3-methylbutanoyl)pyrrolidine-2-carboxamido)-4-methylpentanoate (E24),

4- ((S)-1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-ylamino)-6-(methylamino)-1 ,5,6-trioxohexan-2-ylcarbamoyl)nicotinic acid (E25),

4-((S)-1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-ylamino)-6-(ethylamino)-1 ,5,6-trioxohexan-2-ylcarbamoyl)nicotinic acid (E26),

4-((S)-1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-ylamino)-1 ,5,6-trioxo-6-(pentylamino)hexan-2-ylcarbamoyl)nicotinic acid (E27),

4-((S)-1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclo-hexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-yl-amino)-6-(cyclopropylamino)-1 ,5,6-trioxohexan-2-ylcarbamoyl)nicotinic acid (E28), 4-((S)-1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-ylamino)-6-(benzylamino)-1 ,5,6-trioxohexan-2-ylcarbamoyl)nicotinic acid (E29),

4-((S)-1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-ylamino)-6-(tert-butylamino)-1 ,5,6-trioxohexan-2-ylcarbamoyl)nicotinic acid (E30), 4-((S)-6-amino-1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-ylamino)-1 ,5,6-trioxohexan-2-ylcarbannoyl)nicotinic acid (E31 ),

(S)-N1 -((S)-1 -((S)-2-((S)-2-((S)-2-amino-1 -cyclohexyl-2-oxoethylamino)-1 -cyclohexyl-2-oxoethylcarbamoyl)-4-oxopyrrolidin-1 -yl)-3,3-dimethyl-1 -oxobutan-2-yl)-N6-cyclopropyl-2-(2-methylthiazole-4-carboxamido)-5-oxohexanediamide (E32),

(S)-N1 -((S)-1 -((2R,3S)-1 -((S)-1 -((S)-2-((S)-1 -((S)-2-carbamoylpyrrolidin-1 -yl)-3-(1 H-indol-3-yl)-1 -oxopropan-2-ylcarbamoyl)pyrrolidin-1 -yl)-4-methyl-1 -oxopentan-2-ylamino)-3-nnethyl-1 -oxopentan-2-ylamino)-4-methyl-1 -oxopentan-2-yl)-N6-cyclopropyl-2-(2-methylthiazole-4-carboxannido)-5-oxohexanediannide (E33),

(S)-2-(2-acetamidoacetamido)-N1 -((S)-1 -((2S,3S)-1 -((S)-1 -((S)-2-((S)-1 -amino-3-(1 H-indol-3-yl)-1 -oxopropan-2-ylcarbamoyl)pyrrolidin-1 -yl)-4-methyl-1 -oxopentan-2-ylamino)-3-methyl-1 -oxopentan-2-ylamino)-1 -oxohexan-2-yl)-N6-methyl-5-oxohexanediamide (E34),

(S)-2-(2-((S)-1 -acetylpyrrolidine-2-carboxamido)acetamido)-N1 -((S)-1 -((2S,3S)-1 -((S)-1 -((S)-2-((S)-1 -amino-3-(1 H-indol-3-yl)-1 -oxopropan-2-ylcarbamoyl)pyrrolidin-1 -yl)-4-methyl-1 -oxopentan-2-ylamino)-3-nnethyl-1 -oxopentan-2-ylamino)-1 -oxohexan-2-yl)-N6-methyl-5-oxohexanediannide (E35),

(S)-2-(2-((S)-1 -(2-acetamidoacetyl)pyrrolidine-2-carboxamido)acetamido)-N1 -((S)- 1 -((2S,3S)-1 -((S)-1 -((S)-2-((S)-1 -amino-3-(1 H-indol-3-yl)-1 -oxopropan-2-ylcarbamoyl)pyrrolidin-1 -yl)-4-methyl-1 -oxopentan-2-ylamino)-3-methyl-1 -oxopentan-2-ylamino)-1 -oxohexan-2-yl)-N6-methyl-5-oxohexanediamide (E36),

(S)-2-(2-((S)-1 -(2-((S)-2-acetamido-4-methylpentanamido)acetyl)pyrrolidine-2-carboxamido)acetamido)-N1 -((S)-1 -((2S,3S)-1 -((S)-1 -((S)-2-((S)-1 -amino-3-(1 H-indol-3-yl)-1 -oxopropan-2-ylcarbamoyl)pyrrolidin-1 -yl)-4-methyl-1 -oxopentan-2-ylamino)-3-methyl-1 -oxopentan-2-ylamino)-1 -oxohexan-2-yl)-N6-methyl-5-oxohexanediamide (E37),

(S)-methyl 2-(6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-5-(1 -methyl-1 H-imidazole-5-carboxannido)-2,6-dioxohexanannido)acetat

(E38),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-(methoxynnethyl)-2-(1 -methyl-1 H-imidazole-5-carboxannido)-5-oxohexanediannide (E39),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxo-N6-(thiazol-5-yl)hexanediamide (E40),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxo-N6-(tosylmethyl)hexanediamide (E41 ),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-4-methyl-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxannido)-5-oxohexanediannide (E42),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-5-methyl-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide (E43),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-6-methyl-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide

(E44),

(S)-N1 -(5-chloro-1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide (E45),

(S)-N1 -(5-bromo-1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide (E46),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-5-(trifluoromethyl)-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide (E47),

(S)-1 -methyl-N-(6-(methylamino)-1 ,5,6-trioxo-1 -(4-(phenylsulfonyl)piperazin-1 -yl)hexan-2-yl)-1 H-imidazole-5-carboxamide (E48),

(S)-N1 -(1 -benzylpiperidin-4-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide (E49),

(S)-N1 -(1 -(2-(diethylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl- 2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide (E50),

(S)-N1 -methyl-5-(1 -methyl-1 H-imidazole-5-carboxamido)-N6-(1 -(2-(methylsulfonamido)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-oxohexanediamide (E51 ),

(S)-ethyl 2-(3-(2-(1 -methyl-1 H-imidazole-5-carboxamido)-6-(methylamino)-5,6-dioxohexanamido)-2-oxopyridin-1 (2H)-yl)acetate (E52),

(S)-2-methoxyethyl 2-(3-(2-(1 -methyl-1 H-imidazole-5-carboxamido)-6- (methylamino)-5,6-dioxohexanamido)-2-oxopyridin-1 (2H)-yl)acetate (E53),

(S)-N1 -(1 -(2-(methoxymethylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-5-oxohexanediamide (E54),

(S)-N1 -(1 -(2-((dimethylamino)methylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxannido)-5-oxohexanediannide (E55),

(S)-N1 -(1 -(2-(ethylsulfonamido)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-5-carboxannido)-5-oxohexanediannide (E56),

(S)-benzyl 1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-6-(nnethylannino)-1 ,5,6-trioxohexan-2-ylcarbannate (E57),

(S)-tert-butyl 1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-6-(nnethylannino)-1 ,5,6-trioxohexan-2-ylcarbannate (E58),

(S)-4-(1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-6-(nnethylannino)-1 ,5,6-trioxohexan-2-ylannino)-4-oxobutanoic acid (E59),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-5-oxo-2-((S)-4-oxopyrrolidine-2-carboxamido)hexanediamide (E60),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-2-(furan-3-carboxamido)-N6-nnethyl-5-oxohexanediannide (E61 ),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(oxazole-5-carboxannido)-5-oxohexanediannide (E62),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methylpiperidine-4-carboxamido)-5-oxohexanediamide (E63),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-5-oxo-2-(pynmidine-5-carboxamido)hexanediamide (E64),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-5-oxo-2-(quinoxaline-2-carboxannido)hexanediannide (E65),

(S)-2-(2,4-dimethylthiazole-5-sulfonamido)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-nnethyl-5-oxohexanediannide (E66),

(S)-2-(6-chloroimidazo[2,1 -b]thiazole-5-sulfonamido)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-nnethyl-5-oxohexanediamide (E67),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-2-(1 -methyl-1 H-imidazole-2-sulfonannido)-5-oxohexanediannide (E68),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-5-oxo-2-(3-phenylureido)hexanediannide (E69),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N6-methyl-5-oxo-2-(3-phenylthioureido)hexanediannide (E70),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N7-methyl-2-(1 -methyl-1 H-imidazole-5-carboxannido)-6-oxoheptanediannide (E71 ),

(S)-N1 -methyl-6-(1 -methyl-1 H-imidazole-5-carboxamido)-N7-(4-(4-methylpiperazin-1 -ylsulfonyl)phenyl)-2-oxoheptanediannide (E72),

(S)-N1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-N8-methyl-2-(1 -methyl-1 H-imidazole-5-carboxamido)-7-oxooctanediamide (E73),

(S)-N-(1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-1 ,5,6-trioxoheptan-2-yl)-1 -methyl-1 H-imidazole-5-carboxamide (E74),

(S)-N-(6-cyclopropyl-1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-1 ,5,6-trioxohexan-2-yl)-1 -methyl-1 H-imidazole-5-carboxamide (E75),

(S)-N-(1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-1 ,5,6-trioxo-6-phenylhexan-2-yl)-1 -methyl-1 H-imidazole-5-carboxamide (E76),

(S)-methyl 6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-5-(1 -methyl-1 H-imidazole-5-carboxamido)-2,6-dioxohexanoate (E77),

(S)-2-methoxyethyl 6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-5-(1 -methyl-1 H-imidazole-5-carboxamido)-2,6-dioxohexanoate (E78),

(S)-N1 -(cyclopentylmethoxy)-N6-(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-yl)-5-(1 -methyl-1 H-imidazole-5-carboxamido)-2-oxohexanediamide (E79),

(S)-N-(1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-8-methyl-1 ,5,6-trioxononan-2-yl)-1 -methyl-1 H-imidazole-5-carboxamide (E80),

(S)-N-(1 -(1 -(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1 ,2-dihydropyridin-3-ylamino)-6-(1 -methyl-1 H-imidazol-4-yl)-1 ,5,6-trioxohexan-2-yl)-1 -methyl-1 H-imidazole-5-carboxamide (E81 ),

(2S)-N1 -((S)-1 -((S)-1 -((S)-3-carbamoyl-3,4-dihydroisoquinolin-2(1 H)-yl)-3-(4-hydroxyphenyl)-1 -oxopropan-2-ylamino)-3-(1 H-imidazol-4-yl)-1 -oxopropan-2-yl)-2- (2-(5,5-dimethyl-2-oxotetrahydrofuran-3-yl)acetamido)-N6-methyl-5-oxohexanediamide (E82),

(S)-N1 -(3-((S)-3-(biphenyl-4-yl)-1 -((2S,4R)-2-carbamoyl-4-phenoxypyrrolidin-1 -yl)-1 -oxopropan-2-ylcarbamoyl)phenyl)-2-(2-(1 ,3-dimethyl-1 H-pyrazol-5-yl)acetamido)-N6-methyl-5-oxohexanediamide (E83), and

isopropyl (S)-1 -((S)-1 -(1 -((2S,4R)-2-carbamoyl-4-hydroxypyrrolidin-1 -yl)-2-methyl- 1 -oxopropan-2-ylamino)-5-guanidino-1 -oxopentan-2-ylamino)-6-(methylam

1 ,5,6-trioxohexan-2-ylcarbamate (E84).

Compound according to any one of claims 1 - 10 for use in medicine.

Compound according to any one of claims 1 - 1 1 for use in the treatment or prophylaxis of atherosclerosis, coeliac disease, Duhring-Brocq-disease, gluten ataxia, tissue fibrosis, cystic fibrosis, kidney fibrosis and diabetic nephropathy, liver fibrosis, thrombosis, Huntington's disease, Parkinson's disease, Alzheimer's disease, cataract, ichthyosis, acne, psoriasis, skin aging, and candidosis.

Method for producing compound according to claim 1 comprising:

Step (0): providing a protected amino acid having a chemical warhead;

Step 1 C: deprotecting an amino protecting group PG2 and a carboxyl protecting group PG3;

Step 1 C':

(a) performing coupling reaction of a resulting compound of Step 1 C with a corresponding C-terminal amino acid building block H2ASCl-OPG4;

(b) deprotecting the protecting group PG4;

(c) repeating the steps (a) and (b) i times, wherein i is 1 -8

Step 2C: performing coupling reaction with a C-terminal building block Ec-H; Step 3C: deprotecting an amino protecting group PG1;

Step 4C: performing coupling reaction with a N-terminal building block EN-AG1; to produce the compound of the formula (I).

Method according to claim 13 further comprising the Step 3C' between the step 3B and the step 4C:

Step 3C':

(d) performing coupling reaction of a resulting compound of Step 3C with a corresponding N-terminal amino acid building block (PG5)HASNj-OH;

(e) deprotecting the protecting group PG5;

(f) repeating the steps (a) and (b) j times, wherein j is 1 -4.

Method for producing compound according to claim 1 comprising:

Step (0): providing a protected amino acid (1 C') having a chemical warhead precursor (W);

Step 1 D: performing coupling reaction of the protected amino acid (1 C') with a

C-terminal peptide building block (C-P)

or a C-terminal building block (Ec-H) to obtain a compound 1 D-1 or 1 D-2;

Step 2D: deprotecting an amino protecting group PG1; to obtain a compound 2D- 1 or 2D-2;

Step 3D: performing coupling reaction of the compound 2D-1 or 2D-2 with a N- terminal peptide building block (N-P) or a N-terminal building block (EN- H);

to obtain a compound 3D-1 , 3D-2, 3D-3, or 3D-4;

Step 4D: converting the chemical warhead precursor (W) of the compound 3D- 1 , 3D-2, 3D-3, or 3D-4 to a chemical precursor (W)

to produce a compound 4D-1 , 4D-2, 4D-3, or 4D-4 as compound of the formula (I).