Pharmaceutical uses of ketoamide compounds

Abstract

The present invention relates to a novel use of ketoamide compounds, specifically, the use of the ketoamide compounds of Formula A as 2019 novel coronavirus (2019-nCoV) 3CL protease inhibitors and / or human cathepsin L inhibitors in the preparation of medicaments for treating and / or preventing and alleviating respiratory infections, pneumonia, and other related diseases caused by 2019 novel coronavirus infection. The present invention also relates to the use of pharmaceutical compositions of the compounds, pharmaceutically acceptable salts, enantiomeric forms, diastereomers, and racemates thereof in the preparation of medicaments for treating and / or preventing and alleviating respiratory infections, pneumonia, and other related diseases caused by 2019 novel coronavirus infection. Formula (A): TIFF2023513048000131.tif42170

Description

[Technical field]

[0001] The present invention relates to the field of medicine, specifically to the pharmaceutical use of ketoamide compounds. [Background technology]

[0002] In acute infectious diseases, most are viral infections, which have high morbidity and mortality rates. Due to limited means of detection and diagnosis, new outbreaks caused by new viruses often have sudden, random, and unpredictable characteristics, and once an outbreak occurs, without effective prevention and treatment measures, it can very easily lead to a large-scale epidemic, seriously threatening people's health and safety. Novel coronavirus (2019-nCoV or SARS-CoV-2) infection causes severe pneumonia. The 2019-nCoV virus can be transmitted through droplets and contact, with person-to-person transmission and infection of medical staff, with the risk of community transmission, and the virus may also mutate. At present, there are no specific prevention and treatment methods for novel coronavirus diseases.

[0003] The 2019-nCoV coronavirus is an enveloped, single-stranded, positive-sense RNA virus belonging to the Coronaviridae family, Coronavirus genus. Like other known coronaviruses, the 2019-nCoV coronavirus also completes the proliferation of progeny viruses through several processes, including adsorption, penetration, uncoating, biosynthesis, assembly and release of progeny viruses. The 2019-nCoV coronavirus infection of a host cell begins with the binding of the spike glycoprotein on the surface of the viral envelope to the receptor on the surface of the host cell, followed by membrane fusion, allowing the virus to enter the host cell. Under the action of the cell's organelles, such as lysosomes, the single-stranded positive-sense RNA, which is the genetic material of the virus, is released, and under the action of the host cell's protein synthesis elements, such as mitochondria, ribosomes, and necessary raw materials, polyproteins are produced by translation, and then the papain-like protease (PL), two cysteine ​​proteases essential to the 2019-nCoV coronavirus, is activated. pro ) and 3C-like protease (3CL pro ) cleaves and processes specific polyprotein precursors to generate multiple nonstructural proteins that are important for the viral life cycle. Under the action of these nonstructural proteins, the viral RNA replicates the progeny viral nucleic acid material, translates large amounts of the necessary structural proteins, and completes the assembly and release of progeny viruses. Any link or key enzyme in the life cycle of 2019-nCoV coronavirus-infected cells is the cysteine ​​protease PL, which hydrolyzes and cleaves the polyprotein precursors. pro and 3CL pro , and the RNA polymerase responsible for replicating progeny viral genetic material, can be used as research targets for antiviral drugs.

[0004] Main protease (M pro 3CL protease (also known as 3 chymotrypsin-like protease, 3CL pro3CL is a key protease in the process of hydrolyzing multiple nonstructural proteins after translation of polyproteins pp1a and pp1ab from coronavirus RNA, which is crucial for viral replication and infection. By inhibiting the catalytic function of 3CL protease, the cleavage of viral polyprotein precursors can be effectively inhibited, blocking viral replication and inhibiting the generation of progeny viruses. pro 3CL belongs to the cysteine ​​proteases and is an important protease that catalyzes the proteolysis of single positive-stranded RNA viral precursors and has important effects on the replication activity of coronaviruses such as 2019-nCoV. pro is now recognized as an ideal target for the development of anti-coronavirus drugs.

[0005] Human cathepsin L belongs to the lysosomal papain-like protease family of cysteine ​​proteases, has various biological functions, and as a target, it is widely used in the drug discovery field of anti-parasitic infectious diseases such as Chagas disease caused by trypanosoma infection. Cathepsin L first exists in cells as an inactive zymogen, and needs to be cleaved by itself or activated by other proteases in the acidic environment of endosomes or lysosomes to form a mature enzyme with catalytic activity. A large amount of research has reported that human cathepsin L is closely related to the development of various tumors and also plays an important role in heart disease, and further discovered that human cathepsin is also involved in the infection of host cells by pathogenic microorganisms. There is an increasing evidence that human cathepsin L can be used as a drug target for the development of anti-tumor drugs, heart disease drugs and anti-infective drugs. The spike protein (S protein) of SARS-CoV-2, after being hydrolyzed and activated by host proteases, needs to facilitate the virus' entry into host cells by mediating membrane fusion between the virus and the host cell. According to the different action steps of host proteases, the virus entry pathway can be divided into the surface membrane fusion pathway mediated by type II transmembrane serine protease (TMPRSSII) and the endocytic membrane fusion pathway mediated by human cathepsin L. Thus, these host proteases can all function as entry inhibitors for coronaviruses to enter host cells. Since the inhibition of human cathepsin L can effectively block the virus from entering host cells, human cathepsin L inhibitors are an ideal target for anti-SARS-CoV-2 research and development, and are expected to solve the potential risks and problems of mutation resistance of antiviral drugs targeting the virus.

[0006] Currently, there are no specific vaccines or antiviral drugs against the severe pneumonia caused by the 2019-nCoV coronavirus. These infectious diseases have a serious impact on people's lives and health, and there is an urgent need to develop effective small molecule antiviral drugs. proIt is of great social significance to develop novel, low-toxicity, highly efficient antiviral drugs with independent intellectual property rights against and / or human cathepsin L to meet the clinical needs of patients with 2019-nCoV coronavirus infection at home and abroad.

[0007] In summary, there is an urgent need in the art to develop inhibitors against 2019-nCoV coronavirus 3CL protease and / or human cathepsin L for the treatment of pneumonia caused by novel coronavirus infection. Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a new use of ketoamide compounds.

[0009] Specifically, the present invention provides the use of a ketoamide compound as shown in Formula A as a 2019 novel coronavirus (2019-nCov) 3CL protease inhibitor and / or a human cathepsin L inhibitor in the preparation of a medicament for treating and / or preventing and alleviating respiratory infections, pneumonia and other related diseases caused by 2019 novel coronavirus infection. [Means for solving the problem]

[0010] A first aspect of the present invention provides the use of a ketoamide compound represented by formula (A), or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate thereof, for use in the preparation of (a) a 2019 novel coronavirus (2019-nCov) 3CL protease inhibitor and / or a human cathepsin L inhibitor, and (b) a medicament for the treatment and / or prevention, alleviation of associated diseases caused by 2019 novel coronavirus (2019-nCov) infection, Formula (A): [ka] Where: * denotes that the stereochemical isomerism of the carbon atoms is, independently, R and / or S; R 1 and R 2 are each independently hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 cycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C6 -C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C10 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C10 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C10 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C10 alkenylene group, an acyl group, and a sulfonyl group; R 3 is a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C2-C10 alkenyl group, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 cycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C3-C8 heterocycloalkyl group, a substituted or unsubstituted C3-C8 heterocycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C2 0 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C10 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C10 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C6 alkenylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkynylene group, and a substituted or unsubstituted C3-C20 heteroaryl C2-C6 alkynylene group; R 4is a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C2-C10 alkenyl group, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 arylC1-C 6 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkynylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C9 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkenylene group, and a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkynylene group; R 6 is selected from the group consisting of hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C6 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C9 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkenylene group, an acyl group, and a sulfonyl group; -NR 5 When -(C=O)-CH2- and the adjacent -(C=O)-CH2- form a ring, R 5 is -(CH2) n and n is 2 or 3, -NR 5 does not form a ring with the adjacent -(C=O)-CH2-, R 5is selected from the group consisting of hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C6 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C9 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkenylene group, an acyl group, and a sulfonyl group; Here, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 wherein the substitution refers to substitution by 1, 2, 3 or 4 substituents each independently selected from the group consisting of a halogen, a hydroxyl group, a mercapto group, a nitro group, a cyano group, an amine group, an imine group, a tertiary amine group, an azide group, a C1-C8 alkyl group, a halogenated C1-C8 alkyl group, a C1-C8 alkoxy group, a halogenated C1-C8 alkoxy group, a C1-C6 alkylcarbonyl group, a C1-C6 alkylthio group, a C1-C8 alkoxycarbonyl group, and a trifluoromethyl group, and the heterocycloalkyl group and the heteroaryl group each independently contain 1, 2, 3 or 4 heteroatoms selected from N, O and S.

[0011] In another preferred embodiment, R 6 is H, -NR 5 (or -NR 5 R 6 ) may or may not form an adjacent -(C=O)-CH2- (e.g., a 5- or 6-membered heterocyclic ring). The 5- or 6-membered heterocyclic ring contains one N heteroatom on the ring, and the remaining ring atoms are C. In another preferred example, -NR 5 When -(C=O)-CH2- and the adjacent -(C=O)-CH2- form a ring, R 5is a substituted or unsubstituted -(CH2) n - and n is 2 or 3, wherein the substitution refers to substitution by 1, 2, 3 or 4 substituents each independently selected from the group consisting of a halogen, a hydroxyl group, a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a halogenated C1-C8 alkyl group, a C1-C8 alkoxy group, a halogenated C1-C8 alkoxy group, and a trifluoromethyl group.

[0012] In another preferred embodiment, [ka] The moiety is a substituted or unsubstituted 5- to 6-membered heterocyclic group, wherein the substitution refers to being substituted by 1, 2, 3, or 4 substituents each independently selected from the group consisting of a halogen, a hydroxyl group, a mercapto group, a nitro group, a cyano group, an oxo group, an amine group, an imine group, a tertiary amine group, an azide group, a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a halogenated C1-C8 alkyl group, a C1-C8 alkoxy group, a halogenated C1-C8 alkoxy group, a C1-C6 alkylcarbonyl group, a C1-C6 alkylthio group, a C1-C8 alkoxycarbonyl group, and a trifluoromethyl group, and preferably [ka] The part is [ka] where n1 is 1 or 2. In another preferred embodiment, the associated disease caused by the 2019 novel coronavirus infection is selected from the group consisting of respiratory infections, pneumonia and complications thereof, or a combination thereof.

[0013] In another preferred embodiment, R 1 and R 2are each independently selected from the group consisting of hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 cycloalkyl C1-C5 alkylene group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl C1-C5 alkylene group, a substituted or unsubstituted C6-C14 aryl group, a substituted or unsubstituted C3-C10 heteroaryl group, a substituted or unsubstituted C6-C14 aryl C1-C5 alkylene group, a substituted or unsubstituted C3-C10 heteroaryl C1-C5 alkylene group, a substituted or unsubstituted C6-C10 aryl C2-C5 alkenylene group, a substituted or unsubstituted C3-C10 heteroaryl C2-C5 alkenylene group, an acyl group, and a sulfonyl group; R 3 is a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 cycloalkyl C1-C5 alkylene group, a substituted or unsubstituted C3-C8 heterocycloalkyl group, a substituted or unsubstituted C3-C8 heterocycloalkyl C1-C5 alkylene group, a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted C3-C10 selected from the group consisting of heteroaryl groups, substituted or unsubstituted C6-C10 aryl C1-C5 alkylene groups, substituted or unsubstituted C3-C10 heteroaryl C1-C5 alkylene groups, substituted or unsubstituted C6-C10 aryl C2-C4 alkenylene groups, substituted or unsubstituted C3-C10 heteroaryl C2-C4 alkenylene groups, substituted or unsubstituted C6-C10 aryl C2-C4 alkynylene groups, and substituted or unsubstituted C3-C10 heteroaryl C2-C4 alkynylene groups; Here, R 1 , R 2 and R 3In the above, the substitution refers to being substituted by 1, 2 or 3 substituents each independently selected from the group consisting of a halogen, a hydroxyl group, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group, a C1-C6 alkoxy group, a halogenated C1-C6 alkoxy group, a C1-C4 alkylcarbonyl group, a C1-C4 alkylthio group, a C1-C6 alkoxycarbonyl group, and a trifluoromethyl group, and the heterocycloalkyl group and the heteroaryl group each independently contain 1 or 2 heteroatoms selected from N, O and S.

[0014] In another preferred embodiment, the compound is a compound of formula AA: Formula AA: [ka] Here, R 1 , R 2 , R 3 , R 4 , R 5 and n is as defined above; * denotes that the stereochemical isomerism of the carbon atoms is, independently, R and / or S. In another preferred embodiment, R 4 is selected from the group consisting of a 9-10 membered heteroaromatic ring containing 1, 2 or 3 heteroatoms selected from N, O and S, and a 5-6 membered heteroaromatic ring containing 1, 2 or 3 heteroatoms selected from N, O and S, and the above group is substituted or unsubstituted, where the substitution refers to the hydrogen atoms on the group being substituted with 1, 2, 3 or 4 substituents selected from the group consisting of halogen, hydroxyl group, C1-C6 alkyl group, halogenated C1-C6 alkyl group, C3-C6 cycloalkyl group, halogenated C3-C6 cycloalkyl group, C1-C6 alkoxy group, halogenated C1-C6 alkoxy group, C1-C6 alkylthio group, and halogenated C1-C6 alkylthio group. In another preferred embodiment, R 6is selected from the group consisting of hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, and a substituted or unsubstituted C3-C10 heterocycloalkyl group.

[0015] In another preferred embodiment, the heteroaryl group is a 5-, 6-, 7-, 8-, 9- or 10-membered saturated or partially saturated heteroaromatic ring.

[0016] In another preferred embodiment, the heterocycloalkyl group is a 5-, 6-, 7-, 8-, 9-, or 10-membered unsaturated heterocycle.

[0017] In another preferred embodiment, R 4 teeth, a substituted or unsubstituted quinoxalinyl group, a substituted or unsubstituted quinazolinyl group, a substituted or unsubstituted cinnolinyl group, a substituted or unsubstituted indolyl group, a substituted or unsubstituted isoindolyl group, a substituted or unsubstituted 1,3-benzodioxinyl group; a substituted or unsubstituted benzimidazolyl group, a substituted or unsubstituted indazolyl group, a substituted or unsubstituted imidazo[1,2-A]pyridyl group, a substituted or unsubstituted imidazo[1,5-A]pyridyl group, a substituted or unsubstituted pyrazolyl group, a substituted or unsubstituted imidazolyl group, a substituted or unsubstituted thiazolyl group, a substituted or unsubstituted oxazolyl group, a substituted or unsubstituted isoxazolyl group, a substituted or unsubstituted 1,2,3-triazolyl group, a substituted or unsubstituted 1,2-thiadiazolyl group, a substituted or unsubstituted 1,2,4-triazinyl group, a substituted or unsubstituted pyridyl group, a substituted or unsubstituted pyrrolyl group, a substituted or unsubstituted pyrazinyl group, a substituted or unsubstituted pyrimidinyl group, a substituted or unsubstituted 3,8a-dihydro-2H-benzopyranyl group, a substituted or unsubstituted benzopyranyl group, a substituted or unsubstituted quinolyl group, a substituted or unsubstituted isoquinolyl group, a substituted or unsubstituted benzoxazolyl group, a substituted or unsubstituted benzothiazolyl group, a substituted or unsubstituted benzothienyl group, substituted or unsubstituted benzofuranyl groups; Here, the substitution refers to the replacement of a hydrogen atom on the group with one, two or three substituents selected from the group consisting of F, Cl, Br, I, a hydroxyl group, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group, a C3-C6 cycloalkyl group, a halogenated C3-C6 cycloalkyl group, a C1-C6 alkoxy group, a halogenated C1-C6 alkoxy group, a C1-C6 alkylthio group and a halogenated C1-C6 alkylthio group.

[0018] In this specification, R 4 is an imidazo[1,2-A]pyridine corresponding to the compounds numbered A156 to A161 of the present invention. As used herein, the terms "imidazo[1,2-A]pyridine", "imidazo[1,2-a]pyridine", "imidazo[1,2-A]pyridine" and "imidazo[1,2-a]pyridine" are used interchangeably. As used herein, the terms "imidazo[1,5-A]pyridine", "imidazo[1,5-a]pyridine", "imidazo[1,5-A]pyridine" and "imidazo[1,5-a]pyridine" are used interchangeably. In this specification, R 4 is 3,8a-dihydro-2H-benzopyran corresponding to the compounds numbered A132 to A137 of the present invention.

[0019] In another preferred embodiment, R 6 is H, -NR 5 may or may not form a ring (eg, a 5- to 6-membered heterocycle) with the adjacent -(C=O)-CH2-.

[0020] In another preferred embodiment, -NR 5 (or -NR 5 R 6) forms a ring with the adjacent -(C=O)-CH2-, R 5 is -(CH2) n and n is 3, -NR 5 (or -NR 5 R 6 ) does not form a ring with the adjacent -(C=O)-CH2-, R 5 is selected from the group consisting of hydrogen, deuterium, tritium, a hydroxyl group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 heterocycloalkyl group, a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted C3-C10 heteroaryl group, a substituted or unsubstituted C6-C10 aryl C1-C4 alkylene group, a substituted or unsubstituted C6-C10 aryl C2-C4 alkenylene group, a substituted or unsubstituted C3-C10 heteroaryl C1-C4 alkylene group, and a substituted or unsubstituted C3-C10 heteroaryl C2-C4 alkenylene group; Here, the substitution refers to substitution with 1, 2 or 3 substituents each independently selected from the group consisting of F, Cl, Br, I, a hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, and a C1-C6 alkylthio group, and the heterocycloalkyl group and the heteroaryl group each independently contain 1, 2 or 3 heteroatoms selected from N, O and S.

[0021] In another preferred embodiment, the R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently the corresponding group in the specific compounds (A1-A310) in the Examples.

[0022] In another preferred embodiment, the compound of formula (A) is selected from the group consisting of: [Table 1-1]

Table 1-2

Table 1-3

Table 1-4

Table 1-5

Table 1-6

Table 1-7

Table 1-8

Table 1-9

Table 1-10

Table 1-11

Table 1-12

Table 1-13

Table 1-14

Table 1-15

Table 1-16

Table 1-17

Table 1-18

Table 1-19

Table 1-20

Table 1-21

Table 1-22

Table 1-23

Table 1-24

Table 1-25

Table 1-26

Table 1-27

Table 1-28

Table 1-29

Table 1-30

Table 1-31

Table 1-32

Table 1-33

Table 1-34

Table 1-35

Table 1-36

Table 1-37

Table 1-38

Table 1-39

Table 1-40

Table 1-41

Table 1-42

Table 1-43

Table 1-44

Table 1-45

Table 1-46

Table 1-47

Table 1-48

Table 1-49

Table 1-50

Table 1-51

Table 1-52

[0023] A second aspect of the present invention provides a pharmaceutical composition comprising (a) a therapeutically effective amount of a ketoamide compound of formula (A), or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate or prodrug thereof, and (b) a pharma- ceutically acceptable vector, wherein the ketoamide compound of formula (A) is as described in the first aspect of the present invention.

[0024] A third aspect of the present invention provides the use of the pharmaceutical composition according to the second aspect of the present invention for the preparation of a medicament for the treatment and / or prevention, alleviation of associated diseases resulting from 2019 novel coronavirus (2019-nCov) infection. In another preferred embodiment, the associated disease caused by the 2019 novel coronavirus infection is selected from the group consisting of respiratory infections, pneumonia and complications thereof, or a combination thereof.

[0025] A fourth aspect of the present invention provides a method for treating, preventing, and / or alleviating associated diseases resulting from 2019 novel coronavirus (2019-nCov) infection, comprising administering to a subject in need thereof a safe and effective amount of a ketoamide compound represented by formula (A), or a pharma-ceutically acceptable salt, enantiomer, diastereomer, or racemate thereof, wherein said ketoamide compound represented by formula (A) is as described above. In another preferred embodiment, the subject is a primate mammal, such as a human.

[0026] A fifth aspect of the present invention provides a method for inhibiting the activity of 3CL protease of 2019 novel coronavirus (2019-nCov), comprising the step of inhibiting the activity of 3CL protease of 2019-nCov and / or human cathepsin L by contacting the 3CL protease of 2019-nCov and / or human cathepsin L with a ketoamide compound represented by formula (A), or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate thereof.

[0027] In another preferred embodiment, the method is non-therapeutic and non-diagnostic.

[0028] In another preferred embodiment, the method is in vitro.

[0029] In another preferred embodiment, the 3CL protease of 2019-nCov is a 3CL protease that is recombinant or expressed by 2019-nCov.

[0030] A sixth aspect of the present invention provides a compound of formula (A) according to the first aspect, or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate thereof, Formula (A): [ka] Where: * denotes that the stereochemical isomerism of the carbon atoms is, independently, R and / or S; R 1 and R 2 are each independently hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 cycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C6 -C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C10 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C10 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C10 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C10 alkenylene group, an acyl group, and a sulfonyl group; R 3is a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C2-C10 alkenyl group, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 cycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C3-C8 heterocycloalkyl group, a substituted or unsubstituted C3-C8 heterocycloalkyl C1-C10 alkylene group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C2 0 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C10 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C10 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C6 alkenylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkynylene group, and a substituted or unsubstituted C3-C20 heteroaryl C2-C6 alkynylene group; R 4 is a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C2-C10 alkenyl group, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 arylC1-C 6 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkynylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C9 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkenylene group, and a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkynylene group; R 6is selected from the group consisting of hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C6 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C9 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkenylene group, an acyl group, and a sulfonyl group; -NR 5 When -(C=O)-CH2- and the adjacent -(C=O)-CH2- form a ring, R 5 is -(CH2) n and n is 2 or 3, -NR 5 does not form a ring with the adjacent -(C=O)-CH2-, R 5 is selected from the group consisting of hydrogen, deuterium, tritium, an amino group, a hydroxyl group, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C3-C20 heteroaryl group, a substituted or unsubstituted C6-C20 aryl C1-C6 alkylene group, a substituted or unsubstituted C6-C20 aryl C2-C6 alkenylene group, a substituted or unsubstituted C3-C20 heteroaryl C1-C9 alkylene group, a substituted or unsubstituted C3-C20 heteroaryl C2-C9 alkenylene group, an acyl group, and a sulfonyl group; Here, R 1 , R 2 , R 3 , R 4 , R 5 and R 6wherein the substitution refers to substitution by 1, 2, 3 or 4 substituents each independently selected from the group consisting of a halogen, a hydroxyl group, a mercapto group, a nitro group, a cyano group, an amine group, an imine group, a tertiary amine group, an azide group, a C1-C8 alkyl group, a halogenated C1-C8 alkyl group, a C1-C8 alkoxy group, a halogenated C1-C8 alkoxy group, a C1-C6 alkylcarbonyl group, a C1-C6 alkylthio group, a C1-C8 alkoxycarbonyl group, and a trifluoromethyl group, and the heterocycloalkyl group and the heteroaryl group each independently contain 1, 2, 3 or 4 heteroatoms selected from N, O and S.

[0031] In another preferred embodiment, the compound is a compound of formula AA: Formula AA: [ka] Here, R 1 , R 2 , R 3 , R 4 , R 5 and n is as defined above; * denotes that the stereochemical isomerism of the carbon atoms is, independently, R and / or S.

[0032] In another preferred example, the compounds are compounds A254 to A310 (ie, Examples 254 to 310). Effect of the Invention

[0033] It should be understood that within the scope of the present invention, the above technical features of the present invention and the technical features specifically described below (e.g., in the Examples) can be combined with each other to form new or preferred technical solutions, which will not be repeated here due to space limitations. [Brief description of the drawings]

[0034] [Figure 1]It is shown that the compounds of the present invention can inhibit the replication of 2019nCoV virus. [Diagram 2] 1 shows the inhibition curves and EC50 values ​​of some compounds of the present invention against the 2019 novel coronavirus (2019-nCov). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0035] After extensive and thorough research and extensive screening, the present inventors have unexpectedly developed an active ingredient, namely, a compound shown in formula A or a pharma-ceutically acceptable salt, enantiomer, diastereomer or racemate thereof, that can effectively inhibit the 2019 novel coronavirus (2019-nCov). Tests show that the active ingredient of the present invention can effectively inhibit the activity of 3CL protease and / or human cathepsin L of the 2019 novel coronavirus (2019-nCov), thereby inhibiting the replication and activity of the 2019-nCov. Based on this, the present invention has been completed.

[0036] term As used herein, the terms "novel coronavirus," "2019-nCov," or "SARS-CoV-2" are used interchangeably and refer to the seventh type of coronavirus known to infect humans, causing COVID-19, one of the serious infectious diseases threatening the health of people around the world. Additionally, the terms further include wild-type and mutant viral strains.

[0037] In this specification, unless otherwise stated, the term "substituted" means that one or more hydrogen atoms on a group have been replaced with a C1-C 10 Alkyl groups, C3-C 10 Cycloalkyl groups, C1-C 10 Alkoxy group, halogen, hydroxyl group, carboxyl group (-COOH), C1-C 10 Aldehyde group, C2-C 10 Acyl groups, C2-C 10The phenyl group includes an unsubstituted phenyl group or a substituted phenyl group having 1 to 3 substituents, and the substituents are halogen, C1 to C 10 Alkyl group, cyano group, OH, nitro group, C3~C 10 Cycloalkyl groups, C1-C 10 It is selected from an alkoxy group and an amino group.

[0038] Unless otherwise specified, in all compounds of the present invention, each chiral carbon atom can optionally be of the R or S configuration, or a mixture of R and S configurations.

[0039] The term "C1-C6 alkyl group" refers to a straight or branched chain alkyl group having from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, or similar groups.

[0040] The term "3- to 8-membered heterocyclic group" refers to a group formed by the loss of one hydrogen atom from a 3- to 8-membered saturated ring having 1 to 3 heteroatoms selected from the group consisting of N, S, and O, such as a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a morpholinyl group, or a similar group.

[0041] The term "6- to 10-membered aryl group" refers to a group formed by the loss of one hydrogen atom from a 6- to 10-membered aryl group, for example, a phenyl group, naphthyl group, or the like.

[0042] The term "5- to 10-membered heteroaryl group" refers to a group formed by the loss of one hydrogen atom from a 5- to 8-membered aryl group having from 1 to 3 heteroatoms selected from the group consisting of N, S, and O, where the ring system of each heteroaryl group can be monocyclic or polycyclic, such as, for example, pyrrolyl, pyridyl, thienyl, furyl, imidazolyl, pyrimidinyl, benzothienyl, indolyl, imidazopyridyl, quinolyl, or the like.

[0043] The term "C1-C6 alkoxy" refers to a straight or branched chain alkoxy group having from 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, or similar groups.

[0044] The term "C2-C6 ester group" refers to an ROC(=O)- group having 2 to 6 carbon atoms, such as -COOCH3, -COOC2H5, -COOC3H7, -COOC4H9, or a similar group.

[0045] The term "C2-C6 alkenyl group" refers to a group formed by the loss of one or two hydrogen atoms from an olefin having from 2 to 6 carbon atoms, the olefin being a monoolefin, diolefin, or triolefin, e.g., -CH=CH2, -C2H4=CH2, -CH=C2H4, or a similar group.

[0046] The term "halogen" refers to F, Cl, Br and I.

[0047] Unless otherwise indicated, the structural formulae depicted in the present invention are intended to include all isomers (e.g., enantiomers, diastereomers and geometric isomers (or conformational isomers) such as the R, S configurations, (Z), (E) isomers and (Z), (E) conformational isomers of double bonds, including asymmetric centers. Thus, all individual stereochemical isomers or mixtures of enantiomers, diastereomers or geometric isomers (or conformational isomers) of the compounds of the present invention are within the scope of the present invention.

[0048] The term "tautomer" refers to structural isomers of different energies that can be interconverted across a low energy barrier. For example, proton tautomers (i.e., proton shift) include interconversions via proton migration, such as 1H-indazole and 2H-indazole, 1H-benzo[d]imidazole and 3H-benzo[d]imidazole, and valence tautomers include interconversions via recombination of bonding electrons.

[0049] As used herein, forms such as "C1-C6" indicate that the group in question can have 1 to 6 carbon atoms, for example, 1, 2, 3, 4 or 5 carbon atoms.

[0050] Active ingredients The present invention provides an active ingredient that can effectively inhibit the replication of the 2019 novel coronavirus (2019-nCov), the active ingredient being a compound represented by formula A, which can effectively prevent, treat and / or alleviate 2019-nCov-related diseases.

[0051] The test shows that the active ingredients of the present invention can effectively inhibit the 3CL protease and / or human cathepsin L of the 2019 novel coronavirus (2019-nCov), thereby inhibiting the replication of the 2019 novel coronavirus (2019-nCov), and further preventing, treating and / or alleviating 2019-nCov-related diseases.

[0052] It is to be understood that the active ingredient of the present invention includes the ketoamide compound of formula (A) or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate thereof, or a prodrug thereof. It is to be understood that the active ingredient of the present invention further includes forms such as crystalline forms, amorphous compounds, and deuterated compounds of the compound of formula (A).

[0053] The "pharmaceutically acceptable salts" are the conventional non-toxic salts formed by reaction of the compounds of formula (A) with inorganic or organic acids. For example, conventional non-toxic salts can be prepared by reaction of the compound of formula (A) with an inorganic or organic acid, the inorganic acids including hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, sulfamic acid, and phosphoric acid, and the organic acids including citric acid, tartaric acid, lactic acid, pyruvic acid, acetic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, naphthalenesulfonic acid, ethanesulfonic acid, naphthalenedisulfonic acid, maleic acid, malic acid, malonic acid, fumaric acid, succinic acid, and the like. acid, propionic acid, oxalic acid, trifluoroacetic acid, stearic acid, pamoic acid, hydroxymaleic acid, phenylacetic acid, benzoic acid, salicylic acid, glutamic acid, ascorbic acid, p-aminobenzenesulfonic acid, 2-acetoxybenzoic acid, and isethionic acid.or the sodium, potassium, calcium, aluminum or ammonium salt formed with an inorganic base after ester formation between the compound of formula (A) and propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, aspartic acid or glutamic acid, or the methylamine, ethylamine or ethanolamine salt formed with the compound of formula (A) and an organic base, or the corresponding inorganic acid salt formed with hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid or phosphoric acid after ester formation between the compound of formula (A) and lysine, arginine or ornithine, or the corresponding organic acid salt formed with formic acid, acetic acid, picric acid, methanesulfonic acid or ethanesulfonic acid.

[0054] Pharmaceutical Compositions and Applications The present invention further provides the use of a mixture of one or more species of the ketoamide compound represented by formula (A), or its pharma- ceutically acceptable salts, enantiomers, diastereomers or racemates and prodrugs thereof, as an active ingredient, in the preparation of a medicament for treating and / or preventing, alleviating respiratory infections, pneumonia and other related diseases caused by 2019 novel coronavirus infection.

[0055] The pharmaceutical composition provided by the present invention preferably contains an active ingredient with a weight ratio of 0.001-99 wt%, and the preferred ratio is that the compound of formula A as the active ingredient accounts for 0.1 wt%-90 wt% of the total weight, and the remaining part is a pharma- ceutically acceptable vector, diluent or solution or saline solution.

[0056] If necessary, the drug of the present invention may be added with one or more kinds of pharma- ceutically acceptable vectors, including conventional diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption enhancers, surface active agents, adsorbents, lubricants, etc. in the pharmaceutical field.

[0057] The compounds and pharmaceutical compositions provided by the present invention may be in a variety of forms, such as tablets, capsules, powders, syrups, solutions, suspensions and aerosols, and may be present in suitable solid or liquid vectors or diluents, and in suitable sterile devices for use in injection or infusion.

[0058] Various dosage forms of the pharmaceutical composition of the present invention can be prepared according to conventional preparation methods in the pharmaceutical field.The unit measurement of the preparation usually contains 0.05-400mg of the compound of formula A, preferably 1mg-500mg of the compound of formula A.

[0059] The compounds and pharmaceutical compositions of the present invention can be used clinically in mammals, including humans and animals, by routes of administration such as oral, nasal, dermal, pulmonary or gastrointestinal. Most preferably, it is oral. The most preferred daily dose is 0.01-400 mg / kg body weight in a single dose, or 0.01-200 mg / kg body weight in divided doses. Regardless of the method of administration, the optimal dosage for an individual will vary depending on the specific treatment. It is common to start with a small dose and gradually increase the dosage until the optimal dosage is found.

[0060] The drugs or inhibitors of the present invention can be administered in a variety of ways, for example, by injection, spray, intranasal instillation, eye drop, penetration, absorption, physical or chemical mediation, into the body, such as into the muscle, intraderm, subcutaneous, intravenous, mucosal tissue, etc., or by being mixed or encapsulated in other substances.

[0061] The main advantages of the present invention are: (a) The compounds of the present invention can effectively inhibit 2019-nCoV 3CL protease, with IC of some compounds 50 The value reaches about 2.4 μM. (b) The compounds of the present invention can effectively inhibit human cathepsin L, and the IC 50 The value amounts to approximately 0.45 nM. (c) The inhibition rate of the compounds of the present invention against 2019-nCoV at the viral level was superior to that of the positive control CQ, indicating good anti-2019-nCoV potential, and the EC 50 The value reaches about 0.3 μM. (d) The compounds of the present invention have low toxicity and side effects and good druggability.

[0062] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and do not limit the scope of the present invention. In the following examples, the experimental methods without specific conditions are usually in accordance with conventional conditions or conditions suggested by manufacturers. Unless otherwise specified, percentages and parts are calculated by weight.

[0063] The analytical data of the sample is measured by the following instruments: NMR is measured by GEMINI-300, Bruker AMX-400 and INVOA-600 NMR instruments, TMS (tetramethylsilane) is the internal standard, the chemical shift unit is ppm, the coupling constant unit is Hz, and the mass spectrum is measured by Finnigan MAT-711, MAT-95 and LCQ-DECA mass spectrometers and IonSpec 4.7 Tesla mass spectrometer.

[0064] Silica gel for column chromatography 200-300 mesh (manufactured by Qingdao Ocean Chemical Plant), TLC silica gel plate is HSGF-254 type thin layer chromatography prefabricated plate manufactured by Yantai Chemical Plant, the boiling point range of petroleum ether is 60-90℃, and coloring is performed by ultraviolet light lamp and iodine cylinder. Unless otherwise specified, the conventional reagents and chemicals used in the following examples are purchased from Sinopharm group. All reagents and solvents used in the experiments are treated according to the specific circumstances. EXAMPLES

[0065] Example 1. Compound A1 [ka] Synthesis of compound 1-2: Under argon gas protection, dissolve N-tert-butoxycarbonyl-L-glutamic acid dimethyl ester (1-1) (6 g, 21.8 mmol) in 60 mL of anhydrous tetrahydrofuran, slowly drip LiHMDS (1 M in THF) in tetrahydrofuran (47 mL, 47 mmol) under -78°C conditions, and stabilize and maintain the temperature at -78°C for about 1 hour during the drip. After the drip is completed, stir for 1 hour under -78°C conditions. Dissolve bromoacetonitrile (2.79 g, 23.3 mmol) in 20 mL of tetrahydrofuran, then drip the solution slowly into the reaction system, and continue the dripping process for 1 to 2 hours. Control the temperature at -78°C and continue the reaction for 3 hours. After monitoring the completion of the reaction by TLC (color development of alkaline potassium permanganate), the reaction solution is quenched by adding NH4Cl solution, stirred for 10 minutes, and then warmed to room temperature. 40 mL of saturated sodium chloride solution is poured in and stirred thoroughly, and it is found that the reaction system is separated into layers. The organic layer is separated, the aqueous phase is extracted with ethyl acetate (EA), the organic layers are combined, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (Flash, PE:EA=1:5) to obtain 3.9 g of pale yellow oil 1-2, with a yield of 58%.

[0066] Synthesis of compounds 1-3: 1-2 (1 g, 3.15 mmol) was dissolved in 25 mL of anhydrous methanol, stirred under ice bath until the temperature reached 0 °C, and then added with corbato dichloride hexahydrate (450 mg, 1.89 mmol). After 10 min, a small amount of sodium borohydride (715 mg, 18.9 mmol) was added in batches, and the reaction solution was allowed to react under ice bath for 1 h, and then returned to room temperature. After 15 h, the mixture was quenched with 5 mL of saturated NH4Cl solution, and stirred for 10 min. The solid was removed by filtration, and the filtrate was evaporated to dryness, extracted with 20 mL of water and 30 × 3 mL of ethyl acetate, and the organic phases were combined, dried over anhydrous Na2SO4 for 1 h, concentrated under reduced pressure, and separated by column chromatography [PE:EA = 1:2] to obtain 460 mg of white powdery solid, with a yield of 51%.

[0067] Synthesis of compounds 1-4: Compound 1-3 (2.6 g) was dissolved in a solution of trifluoroacetic acid in dichloromethane (1 / 1, v / v), stirred at room temperature for 1 hour, concentrated, and then added with 100 mL of dichloromethane, washed with saturated sodium carbonate solution, and the organic layer was dried over anhydrous sodium sulfate and concentrated to obtain oily product 1-4 (2.7 g), with a yield of 99%.

[0068] Synthesis of compounds 1-5: Boc-cyclohexylalanine (1.26g, 5mmol), EDCI (1.36g, 6mmol), HOBt (0.822g, 6mmol) are added to 80mL of dichloromethane solution and stirred at room temperature for 30 minutes. Then compound 1-4 (0.896g, 5mmol) is added, 1.2 equivalents of triethylamine are added dropwise, and stirred at room temperature. After monitoring the completion of the reaction by TLC (ultraviolet), it is extracted with dichloromethane, washed with dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride, and the organic layer is combined, dried with anhydrous sodium sulfate, and concentrated to obtain 1.2g of a white viscous solid, the yield is 60%.

[0069] Synthesis of compounds 1-6: Compound 1-5 (2.5 g) was dissolved in a solution of trifluoroacetic acid in dichloromethane (1 / 1, v / v), stirred at room temperature for 1 hour, concentrated, and then added with 100 mL of dichloromethane, washed with saturated sodium carbonate solution, and the organic layer was dried over anhydrous sodium sulfate and concentrated to obtain oily product 1-6 (2.61 g), with a yield of 99%.

[0070] Synthesis of compounds 1-7: Indole 2-carboxylic acid (0.795g, 5mmol), EDCI (1.36g, 6mmol), HOBt (0.822g, 6mmol) are added to 80mL of dichloromethane solution and stirred at room temperature for 30 minutes. Compound 1-6 (2.2g, 5mmol) is then added, 1.2 equivalents of triethylamine are added dropwise, and stirred at room temperature. After monitoring the completion of the reaction by TLC (ultraviolet), it is extracted with dichloromethane, washed with dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride, and the organic layer is combined, dried over anhydrous sodium sulfate, and concentrated to obtain 1.3g of a white viscous solid, the yield is 60%.

[0071] Synthesis of compounds 1-8: 1-7 (243 mg, 0.51 mmol) was dissolved in 20 mL of methanol, and sodium borohydride (107 mg, 2.9 mmol) was added slowly in batches. The reaction was completed by stirring at room temperature for about 2 hours. After the reaction was completed, the reaction was quenched by adding about 20 mL of saturated saline solution, and the reaction system was concentrated with methanol and extracted with dichloromethane. The organic phase was washed with saturated saline solution, dried over anhydrous sodium sulfate, and concentrated to give a white solid material 1-8, which was used directly in the next step.

[0072] Synthesis of compounds 1-9: Intermediate 1-8 (129 mg, 0.29 mmol) was dissolved in 20 mL of dichloromethane solution, Dess-Martin oxidant (147 mg, 0.35 mmol) and solid sodium bicarbonate (29 mg, 0.35 mmol) were added, and the mixture was stirred at room temperature. After monitoring the completion of the reaction by TLC (ultraviolet light), the reaction system was suction filtered, and the obtained filtrate was extracted with saturated sodium bicarbonate solution, and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and then concentrated. Separation and purification were performed by flash column chromatography (CH2Cl2:MeOH=20:1) to obtain a total of 77 mg of white solid powder compound 1-9, with a yield of 60%.

[0073] Synthesis of compounds 1-10: Compound 1-9 (129 mg, 0.29 mmol) was dissolved in dichloromethane solvent, and acetic acid (19.2 mg, 0.32 mmol) and benzyl isocyanide (37.6 mg, 0.32 mmol) were added and reacted to obtain compound 1-10, which was separated and purified by flash column chromatography (CH2Cl2:MeOH=20:1) to obtain a total of 126 mg of white solid powder compound 1-10, the yield is 70%.

[0074] Synthesis of compounds 1-11: Compound 1-10 (187 mg, 0.3 mmol) was dissolved in methanol solvent, and LiOH (0.6 mmol) was added and stirred to obtain compound 1-11. Compound 1-11 was separated and purified by flash column chromatography (CH2Cl2:MeOH=20:1) to obtain a total of 148 mg of white solid powder compound 1-11, the yield is 85%.

[0075] Synthesis of compounds 1-12: Compound 1-11 (174 mg, 0.3 mmol) was dissolved in dichloromethane solvent, Dess-Martin oxidant (152 mg, 0.36 mmol) was added, sodium bicarbonate (30 mg, 0.36 mmol) was added, and the mixture was stirred to obtain a total of 140 mg of white solid powder compound 1-12, the yield being 80%. 1H NMR (500 MHz, Chloroform) δ 9.76 (s, 1H), 7.73 (s, 1H), 7.39 (s, 1H), 7.32-7.26 (m, 2H), 7.22 (s, 1H), 7.20-7.10 (m, 3H), 7.01 (s, 1H), 6.82 (s, 1H), 6.68 (s, 1H), 6.14 (s, 1H), 5.57 (s, 1H), 5.43 (s, 1H), 4.38 (s, 1H), 4.3 2(d, J=19.2Hz, 2H), 3.45(s, 1H), 3.35(s, 1H), 3.06(s, 1H), 2.20(dd, J=15.4, 2.3Hz, 4H), 2.1 2-2.03(m, 2H), 1.92(s, 1H), 1.77(s, 1H), 1.73-1.67(m, 3H), 1.66-1.53(m, 6H), 1.37(s, 1H).

[0076] Using a method similar to that of Example 1, Examples 2-310 are synthesized.

[0077] Example 2. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A2) 1 H NMR (500 MHz, chloroform) δ 8.38 (s, 1H), 7.51 (d, J = 18.0 Hz, 2H), 7.38 (s, 1H), 7.12 (s, 1H), 7.06 (s, 1H), 6.26 (s, 1H), 6.04 (s, 1H), 5.80 (s, 1H), 5.25 (s, 1H), 4.81 (s, 1H), 4.67 (s, 1H), 3.45 ( s, 1H), 3.35(s, 1H), 2.55(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.96-1.91(m, 3 H), 1.73-1.52(m, 5H), 1.40-1.36(m, 2H), 1.35-1.29(m, 10H), 1.20-1.09(m, 3H).

[0078] Example 3. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A3) 1 H NMR (500 MHz, chloroform) δ 8.28 (s, 1H), 7.48 (d, J = 1.2 Hz, 2H), 7.34 (s, 1H), 7.10 (d, J = 1.0 Hz, 2H), 7.03 (s, 1H), 6.05 (s, 1H), 5.59 (s, 1H), 5.30 (s, 1H), 4.63 (s, 1H), 4.45 (s, 1H), 3.58 (s, 1H), 3.45 (s, 1H), 3.35 (s , 1H), 2.95(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.98-1.90(m, 3H), 1.73-1.67(m, 3H), 1. 65-1.61(m, 2H), 1.51(dtd, J=12.9, 8.9, 1.3Hz, 13H), 1.45-1.39(m, 3H), 1.38-1.34(m, 2H).

[0079] Example 4. N-((S)-3-cyclohexyl-1-(((S)-4-(neopentylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A4) 1H NMR (500MHz, chloroform)δ 8.46(s, 1H), 7.53(d, J=3.4Hz, 2H), 7.40(d, J=17.1Hz, 2H), 7.12(s, 1H), 7.06(s, 1H), 6.16( d, J=14.3Hz, 2H), 5.65(s, 1H), 5.23(s, 1H), 4.44(s, 1H), 3.44(d, J=11.4Hz, 2H), 3.35(s, 1H) , 3.09(s, 1H), 2.97(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H), 1.75-1.68(m, 4H), 1 .62(s, 1H), 1.48(dt, J=16.0, 8.0Hz, 5H), 1.37-1.31(m, 2H), 1.28(s, 1H), 1.09-1.05(m, 9H).

[0080] Example 5. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A5) 1 H NMR (500 MHz, chloroform) δ 8.22 (s, 1H), 7.96 (s, 1H), 7.53 (s, 1H), 7.42 (s, 1H), 7.38 (s, 1H), 7.29-7.24 (m, 4H), 7.17 (d, J = 29.6 Hz, 2H), 7.07 (s, 1H), 6.54 (s, 1H), 5.74 (s, 1H), 5.27 (s, 1H), 5.06 (s, 1H), 4.49 (s, 1H), 4.41 (s, 1H), 4.31 (s, 1H), 3.24(d, J=17.4Hz, 2H), 2.56(s, 1H), 2.08-2.04(m, 2H), 1.95-1.88(m, 2H), 1.78(d, J=6.9Hz, 2H), 1 .69(dt, J=6.3, 3.5Hz, 7H), 1.51(s, 1H), 1.40-1.36(m, 2H), 1.32(s, 1H), 1.15-1.11(m, 2H), 1.08(s, 1H).

[0081] Example 6. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A6) 1 H NMR (500MHz, chloroform)δ 8.30(s, 2H), 7.48(s, 2H), 7.43(s, 2H), 7.35(s, 2H), 7.10(s, 2H), 7.03(s, 2H), 6.45(s, 2H) , 5.99(s, 2H), 5.76(s, 2H), 5.25(s, 2H), 4.81(s, 2H), 4.29(s, 2H), 3.24(d, J=17.1Hz, 4H), 2.75(s, 2H), 2.05(t, J=8.9Hz, 6H), 1.79(s, 2H), 1.71(t, J=2.5Hz, 7H), 1.58-1.54(m, 3H), 1.51-1.33(m, 10H), 1.33-1.29(m, 20H), 1.23(s, 2H), 1.15-1.11(m, 3H), 0.94-0.90(m, 3H).

[0082] Example 7. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A7) 1H NMR (500MHz, chloroform)δ 9.29(s, 1H), 8.69(s, 1H), 7.52(s, 1H), 7.43(d, J=15.1Hz, 2H), 7.13(s, 1H), 7.06(s, 1H), 5.93(s, 1H), 5.59(d, J=3.5Hz, 2H), 5.11(s, 1H), 4.51(s, 1H), 3.41(s, 1H), 3.24(d, J=16.6Hz, 2H), 2.66(s, 1H), 2.54(s, 1H), 2.08-2.04(m, 2H), 2.01-1.89(m, 2H), 1.89-1.77(m, 4H), 1.73-1.61(m, 7H), 1.5 5-1.50(m, 3H), 1.48(s, 1H), 1.44-1.39(m, 2H), 1.39-1.35(m, 2H), 1.31(s, 1H), 1.09-0.99(m, 3H).

[0083] Example 8. N-((S)-3-cyclohexyl-1-(((S)-4-(neopentylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A8) 1 H NMR (500MHz, chloroform)δ 8.45(s, 4H), 7.50(d, J=31.7Hz, 8H), 7.46-7.46(m, 1H), 7.39(s, 5H), 7.13(s, 4H), 7.06(s, 4H), 6.0 1(s, 4H), 5.44(s, 4H), 5.40(s, 4H), 5.23(s, 4H), 4.89(s, 4H), 4.47(s, 4H), 3.30-3.20(m, 12H), 3.1 3(s, 4H), 2.30(s, 4H), 2.10-2.02(m, 8H), 1.97(s, 3H), 1.81-1.76(m, 11H), 1.71(t, J=1.6Hz, 11H), 1.69-1.63(m, 13H), 1.50(s, 3H), 1.39-1.35(m, 7H), 1.31(s, 4H), 1.14-1.05(m, 44H), 1.02(s, 3H).

[0084] Example 9. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A9) 1 H NMR (500 MHz, chloroform) δ 7.66 (s, 1H), 7.34-7.28 (m, 5H), 7.22 (d, J = 7.1 Hz, 2H), 7.10 (s, 1H), 6.72 (s, 1H), 6.17 (s, 1H), 5.97 (s, 1H), 5.84 (s, 1H), 5.47 (s, 1H), 4.42 (s, 1H), 4.34 (d, J = 9.3 Hz, 2H) , 3.45(s, 1H), 3.35(s, 1H), 3.22(s, 1H), 2.64(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H) , 2.05-1.98(m, 2H), 1.92(s, 1H), 1.75-1.66(m, 4H), 1.66-1.55(m, 6H), 1.36(s, 1H).

[0085] Example 10. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A10) 1 H NMR (500 MHz, chloroform) δ 9.59 (s, 1H), 8.31 (s, 1H), 7.63 (s, 1H), 7.50 (s, 1H), 7.41 (s, 1H), 7.22 (s, 1H), 7.16 (s, 1H), 6.40 (s, 1H), 5.82 (s, 1H), 4.81 (s, 1H), 4.64 (s, 1H), 3.97 (s, 1H), 3.35 (s, 1H) , 2.69(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.94-1.88(m, 3H), 1.76-1.66(m, 2H), 1.66-1.48(m, 3H), 1.36-1.32(m, 11H), 1.28(s, 1H), 1.20(s, 1H), 0.99-0.95(m, 2H).

[0086] Example 11. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A11) 1 H NMR (500MHz, chloroform)δ 7.63(s, 4H), 7.47(s, 4H), 7.36(s, 4H), 7.26(s, 4H), 7.21(s, 4H), 7.14(s, 4H), 5.98(s, 4H) ), 5.77(s, 4H), 5.16(s, 4H), 4.60(s, 4H), 4.32(s, 4H), 3.53(s, 3H), 3.45(s, 4H), 3.35(s, 3 H), 2.58(s, 3H), 2.19(s, 3H), 2.09-2.05(m, 8H), 1.95-1.88(m, 11H), 1.74-1.68(m, 27H), 1.65-1.61(m, 6H), 1.61-1.47(m, 31H), 1.44-1.39(m, 8H), 1.35-1.31(m, 6H), 1.24(s, 3H).

[0087] Example 12. N-((S)-3-cyclohexyl-1-(((S)-4-(neopentylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A12) 1H NMR (500MHz, chloroform)δ 8.31(s, 4H), 7.60(s, 4H), 7.49(s, 4H), 7.40(s, 4H), 7.21(s, 4H), 7.15(s, 4H), 6.18(s, 4H), 5.4 6(s, 4H), 5.25(s, 4H), 5.12(s, 4H), 4.63(s, 4H), 3.43(d, J=18.9Hz, 8H), 3.35(s, 3H), 3.11(s, 4) H), 2.76(s, 4H), 2.17(s, 3H), 2.13-2.01(m, 8H), 1.93(s, 4H), 1.85-1.81(m, 6H), 1.73-1.69(m, 7H), 1.69-1.62(m, 7H), 1.61-1.42(m, 16H), 1.33-1.29(m, 6H), 1.26(s, 3H), 1.14-1.10(m, 3H).

[0088] Example 13. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A13) 1 H NMR (500MHz, chloroform)δ 7.59(s, 4H), 7.51(d, J=1.4Hz, 1H), 7.46(d, J=36.6Hz, 7H), 7.32-7.14(m, 29H), 6.56(s, 4 H), 5.75(s, 4H), 5.66(s, 4H), 5.09(s, 4H), 4.56(s, 4H), 4.41(s, 4H), 4.32(s, 4H), 3.24(d , J=17.0Hz, 8H), 2.32(s, 4H), 2.10-2.02(m, 9H), 1.99(s, 4H), 1.97-1.89(m, 8H), 1.79(s, 4H), 1.75-1.52(m, 28H), 1.40-1.36(m, 7H), 1.32(s, 4H), 1.23-1.19(m, 8H), 1.16(s, 3H).

[0089] Example 14. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A14) 1 H NMR (500 MHz, chloroform) δ 7.63 (s, 1H), 7.50 (s, 1H), 7.37 (s, 1H), 7.22 (s, 1H), 7.16 (s, 1H), 6.25 (s, 1H), 6.08 (s, 1H), 5.76 (s, 1H), 4.70 (d, J = 19.7 Hz, 2H), 3.24 (d, J = 14.7 Hz, 2H ), 2.83(s, 1H), 2.08-2.04(m, 2H), 2.01(s, 1H), 1.90(s, 1H), 1.85-1.78(m, 3H), 1.75-1.64(m, 5H), 1.56-1.41(m, 6H), 1.32(s, 1H), 1.25-1.21(m, 9H).

[0090] Example 15. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A15) 1 H NMR (500 MHz, chloroform) δ 9.45 (s, 1H), 8.16 (s, 1H), 7.51 (s, 1H), 7.42 (s, 1H), 7.22 (s, 1H), 7.16 (s, 1H), 6.16 (s, 1H), 6.07 (s, 1H), 5.85 (s, 1H), 5.08 (s, 1H), 4.48 (s, 1H), 3.32 (s, 1H), 3.24 (d, J = 16.1 Hz, 2H), 2.92 (s, 1H) , 2.16-2.08(m, 2H), 2.08-2.04(m, 2H), 2.02(s, 1H), 1.80(s, 1H), 1.76-1.66(m, 8H), 1.65(s, 1H) , 1.57(s, 1H), 1.55-1.40(m, 8H), 1.40-1.37(m, 1H), 1.31(s, 1H), 1.12(s, 1H), 0.90-0.82(m, 2H).

[0091] Example 16. N-((S)-3-cyclohexyl-1-(((S)-4-(neopentylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A16) 1 1 H NMR (500 MHz, chloroform) δ 7.60 (s, 1H), 7.49 (s, 1H), 7.40 (s, 1H), 7.21 (s, 1H), 7.15 (s, 1H), 6.20 (s, 1H), 5.99 (s, 1H), 5.91 (s, 1H), 5.65 (s, 1H), 4.86 (s, 1H), 4.76 (s, 1H), 3.30 (s, 1H), 3.24 (d, J = 17.4 Hz, 2H), 2.92 ( s, 1H), 2.65(s, 1H), 2.08-2.04(m, 2H), 2.01(s, 1H), 1.90-1.84(m, 2H), 1.82(s, 1H), 1.77-1. 65(m, 5H), 1.60-1.53(m, 4H), 1.52-1.48(m, 2H), 1.40(s, 1H), 1.34(s, 1H), 1.07-1.03(m, 9H).

[0092] Example 17. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzothiophene-2-carboxamide (A17) 1H NMR (500MHz, chloroform)δ 8.13(s, 5H), 7.89(s, 5H), 7.65(s, 5H), 7.28(dd, J=7.5, 4.2Hz, 20H), 7.21(dd, J=4.2, 2.6H z, 2H), 7.20-7.08(m, 13H), 6.14(s, 5H), 5.53(s, 5H), 5.37(s, 5H), 4.39-4.32(m, 15H), 4.2 4(s, 5H), 3.45(s, 5H), 3.35(s, 4H), 3.24(s, 5H), 2.94(s, 4H), 2.19(s, 4H), 2.09-2.05(m, 1 0H), 1.92(s, 4H), 1.80-1.67(m, 25H), 1.59-1.49(m, 15H), 1.46-1.38(m, 19H), 1.23(s, 5H).

[0093] Example 18. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzothiophene-2-carboxamide (A18) 1 H NMR (500 MHz, chloroform) δ 8.37 (s, 1H), 7.89 (s, 1H), 7.73 (s, 1H), 7.31 (d, J = 1.5 Hz, 2H), 6.28 (s, 1H), 6.05 (s, 1H), 5.80 (s, 1H), 5.25 (s, 1H), 4.82 (s, 1H), 4.68 (s, 1H), 3.45 (s, 1H), 3.35(s, 1H), 2.56(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.95-1.88(m, 3H), 1.73-1.52(m, 5H), 1.41-1.37(m, 2H), 1.35-1.29(m, 10H), 1.18-1.09(m, 3H).

[0094] Example 19. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzothiophene-2-carboxamide (A19) 1 H NMR (500 MHz, chloroform) δ 8.95 (s, 1H), 8.43 (s, 1H), 8.26 (s, 1H), 7.90 (s, 1H), 7.74 (s, 1H), 7.61 (s, 1H), 7.31 (d, J = 2.0 Hz, 2H), 5.94 (s, 1H), 4.69 (s, 1H), 4.53 (s, 1H), 3.44 (d, J = 9.6 Hz, 2H), 3.35 (s, 1H), 2.95 (s, 1H), 1.06 (s, 1H), 1.05 (s, 1H), 1.04 (s, 1H), 1.03 (s, 1H), 1.02 (s, 1H), 1.01 ... H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.91(t, J=7.7Hz, 3H), 1.75-1.68(m, 5H), 1.68-1.63(m, 2 H), 1.62-1.58(m, 2H), 1.58-1.46(m, 8H), 1.45-1.40(m, 2H), 1.22-1.14(m, 2H), 1.07(s, 1H).

[0095] Example 20. N-((S)-3-cyclohexyl-1-(((S)-4-(neopentylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzothiophene-2-carboxamide (A20) 1 H NMR (500 MHz, chloroform) δ 8.36 (s, 1H), 7.88 (s, 1H), 7.73 (s, 1H), 7.30 (d, J = 2.5 Hz, 2H), 6.53 (s, 1H), 6.04 (s, 1H), 5.82 (s, 1H), 5.52 (s, 1H), 4.68 (d, J = 6.4 Hz, 2H), 3.45 (s, 1H), 3.35 (d, J = 3 .1Hz, 2H), 2.90(s, 1H), 2.43(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.91(t, J=5 .9Hz, 3H), 1.74-1.65(m, 4H), 1.60-1.51(m, 6H), 1.34(s, 1H), 1.08-1.04(m, 9H).

[0096] Example 21. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzothiophene-2-carboxamide (A21) 1 H NMR (500 MHz, chloroform) δ 8.31 (s, 1H), 7.92 (s, 1H), 7.74 (s, 1H), 7.34-7.23 (m, 6H), 7.20 (s, 1H), 6.76 (s, 1H), 5.59 (s, 1H), 5.49 (s, 1H), 5.08 (s, 1H), 4.52 (s, 1H), 4.42 (s, 1H), 4.34 (s, 1H), 3.24 (d, J = 17.6 Hz, 2H), 2.68(s, 1H), 2.08-2.04(m, 2H), 1.74-1.67(m, 5H), 1.64(dd, J=2.9, 1.7Hz, 4H), 1 .36-1.32(m, 2H), 1.30(s, 1H), 1.26(s, 1H), 1.17(s, 1H), 1.13-1.05(m, 2H), 0.98(s, 1H).

[0097] Example 22. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzothiophene-2-carboxamide (A22) 1 H NMR (500 MHz, chloroform) δ 8.34 (s, 1H), 8.22 (s, 1H), 7.88 (s, 1H), 7.72 (s, 1H), 7.30 (d, J = 1.5 Hz, 2H), 6.15 (s, 1H), 6.10 (s, 1H), 5.41 (s, 1H), 4.64 (d, J = 11.7 Hz, 2H), 3.24 (d, J = 14.8 Hz, 2H), 2.90(s, 1H), 2.11-2.01(m, 2H), 1.89-1.81(m, 4H), 1.77(s, 1H), 1.73-1.6 8(m, 4H), 1.66-1.59(m, 5H), 1.55-1.49(m, 2H), 1.35(s, 1H), 1.32-1.28(m, 9H).

[0098] Example 23. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzothiophene-2-carboxamide (A23) 1 H NMR (500 MHz, chloroform) δ 8.93 (s, 1H), 8.55 (s, 1H), 7.91 (s, 1H), 7.72 (s, 1H), 7.30 (d, J = 2.6 Hz, 2H), 6.05 (s, 1H), 5.83 (s, 1H), 5.68 (s, 1H), 5.13 (s, 1H), 4.34 (s, 1H), 3.33 (s, 1H), 3.24 (d, J = 15.0 Hz, 2H), 2.73 (s , 1H), 2.43(s, 1H), 2.08-2.04(m, 5H), 1.85(s, 1H), 1.78(s, 1H), 1.73-1.67(m, 5H), 1.66-1.5 2(m, 7H), 1.51(s, 2H), 1.44-1.39(m, 3H), 1.34-1.30(m, 2H), 1.27(s, 1H), 0.83-0.72(m, 2H).

[0099] Example 24. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A24) 1H NMR (500MHz, chloroform)δ 7.61(s, 2H), 7.40-7.26(m, 10H), 7.18(dd, J=24.7, 8.9Hz, 9H), 6.51(s, 2H), 6.14(s, 2H), 5 .17(s, 2H), 4.61(s, 2H), 4.40(s, 2H), 4.27(s, 2H), 4.19(s, 2H), 3.60-3.56(m, 6H), 3.52(s , 2H), 3.45(s, 2H), 3.35(s, 2H), 2.87(s, 2H), 2.18(s, 2H), 2.09-2.05(m, 4H), 1.92(s, 2H), 1.73-1.69(m, 4H), 1.60-1.50(m, 11H), 1.36-1.32(m, 3H), 1.18(s, 2H), 1.07-1.03(m, 3H).

[0100] Example 25. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A25) 1 H NMR (500 MHz, chloroform) δ 7.40 (s, 1H), 7.27 (d, J = 5.4 Hz, 2H), 7.18 (d, J = 11.2 Hz, 2H), 6.05 (d, J = 0.5 Hz, 2H), 5.79 (s, 1H), 5.25 (s, 1H), 4.80 (s, 1H), 4.65 (s, 1H), 3.88-3.84 (m, 3H), 3.45 (s , 1H), 3.35(s, 1H), 2.58(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.95-1.91(m, 3 H), 1.73-1.52(m, 5H), 1.41-1.37(m, 2H), 1.35-1.29(m, 10H), 1.19-1.09(m, 3H).

[0101] Example 26. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A26) 1 H NMR (500 MHz, chloroform) δ 7.24 (s, 1H), 7.17 (s, 1H), 7.12 (d, J = 0.8 Hz, 2H), 7.05 (s, 1H), 6.01 (s, 1H), 5.68 (d, J = 17.0 Hz, 2H), 4.92 (s, 1H), 4.81 (s, 1H), 3.98 (s, 1H), 3.81 (s, 1H), 3.74-3.70 (m, 3H). , 3.35(s, 1H), 2.62(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.95-1.91(m, 3H), 1.90- 1.77(m, 4H), 1.73-1.69(m, 2H), 1.66-1.54(m, 13H), 1.39-1.35(m, 2H), 1.33(s, 1H).

[0102] Example 27. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A27) 1 H NMR (500 MHz, chloroform) δ 7.43 (s, 1H), 7.38-7.24 (m, 7H), 7.20 (d, J = 8.0 Hz, 2H), 5.93 (s, 1H), 5.87 (s, 1H), 5.57 (s, 1H), 5.47 (s, 1H), 4.73 (s, 1H), 4.55 (s, 1H), 4.39 (d, J = 18.9 Hz, 2H), 3.61-3.57 (m, 3H). , 3.23(d, J=15.5Hz, 2H), 2.08-2.04(m, 2H), 1.96-1.92(m, 3H), 1.85(s, 1H), 1.73-1.64( m, 6H), 1.61(s, 1H), 1.41(t, J=7.7Hz, 3H), 1.32(s, 1H), 1.24(s, 1H), 1.14-1.07(m, 2H).

[0103] Example 28. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A28) 1 H NMR (500MHz, chloroform)δ 7.46(s, 47H), 7.26(d, J=19.3Hz, 98H), 7.17(d, J=7.3Hz, 95H), 6.39(s, 47H), 5.92(d, J=11.5H) z, 95H), 5.44(s, 47H), 4.71(s, 46H), 4.53(s, 46H), 3.74-3.70(m, 141H), 3.24(d, J=18.1Hz, 90H ), 2.77(s, 44H), 2.11-2.01(m, 97H), 1.91(s, 34H), 1.81(s, 43H), 1.77-1.69(m, 222H), 1.66-1. 62(m, 70H), 1.61-1.42(m, 241H), 1.49-1.42(m, 10H), 1.40-1.36(m, 70H), 1.32-1.22(m, 478H).

[0104] Example 29. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A29) 1H NMR (500 MHz, chloroform) δ 7.41 (s, 1H), 7.35-7.22 (m, 2H), 7.19 (d, J = 7.5 Hz, 2H), 5.92 (s, 1H), 5.54 (s, 1H), 5.38 (s, 1H), 5.23 (s, 1H), 5.04 (s, 1H), 4.34 (s, 1H), 3.99-3.95 (m, 3H), 3.86 (s, 1H), 3.24 (d, J =15.7Hz, 2H), 2.86(s, 1H), 2.08-2.02(m, 4H), 1.99(s, 1H), 1.81(s, 1H), 1.78-1.67(m, 7 H), 1.66-1.51(m, 10H), 1.43(s, 1H), 1.41-1.37(m, 2H), 1.30(s, 1H), 0.77-0.70(m, 2H).

[0105] Example 30. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A30) 1 H NMR (500 MHz, chloroform) δ 7.87 (s, 1H), 7.29 (t, J = 9.9 Hz, 3H), 7.22-7.11 (m, 2H), 6.98 (s, 1H), 6.61 (s, 1H), 6.43 (s, 1H), 6.20 (s, 1H), 5.62 (s, 1H), 4.55 (s, 1H), 4.43 (d, J = 15.9 Hz, 2H), 4.32 (s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.12(s, 1H), 2.33(s, 1H), 2.18(s, 1H), 2.09-2 .05(m, 2H), 1.94-1.88(m, 3H), 1.74-1.66(m, 4H), 1.63-1.55(m, 6H), 1.35(s, 1H).

[0106] Example 31. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A31) 1 H NMR (500 MHz, chloroform) δ 9.04 (s, 1H), 8.68 (s, 1H), 8.53 (s, 1H), 7.42 (s, 1H), 7.38 (s, 1H), 7.06 (s, 1H), 6.78 (s, 1H), 5.77 (s, 1H), 4.93 (s, 1H), 4.55 (s, 1H), 3.99 (s, 1H), 3.35 (s, 1H), 2 .63(s, 1H), 2.19(s, 1H), 2.10-2.04(m, 4H), 1.93(s, 1H), 1.69(dt, J=18.2, 9.1 Hz, 5H), 1.41-1.37(m, 2H), 1.35-1.27(m, 11H), 1.24(s, 1H), 1.05-1.01(m, 2H).

[0107] Example 32. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A32) 1 H NMR (500 MHz, chloroform) δ 8.86 (s, 1H), 8.48 (s, 1H), 7.54 (s, 1H), 7.41 (s, 1H), 7.06 (s, 1H), 6.01 (s, 1H), 5.47 (s, 1H), 5.20 (s, 1H), 5.05 (s, 1H), 4.55 (s, 1H), 4.00 (s, 1H), 3.58 (s, 1H), 3.51 (s, 1H), 3.35(s, 1H), 2.19(s, 1H), 2.12-2.02(m, 2H), 2.00-1.96(m, 2H), 1.94-1. 87(m, 3H), 1.73-1.46(m, 14H), 1.40-1.36(m, 2H), 1.32(s, 1H), 1.12-1.06(m, 3H).

[0108] Example 33. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A33) 1 H NMR (500MHz, chloroform)δ 8.68(s, 11H), 7.45(s, 11H), 7.38(s, 11H), 7.31-7.23(m, 34H), 7.23-7.17(m, 26H), 7.16(s, 8H), 7.11(s, 11H), 5.89(s, 11H), 5.79(s, 11H), 4.76(s, 11H), 4.51(s, 11H), 4.35(s, 11H), 4.29(s, 11H), 3.24(d, J=17. 5Hz, 21H), 2.73(s, 11H), 2.10-2.04(m, 23H), 2.02(s, 9H), 1.83(s, 10H), 1.81-1.74(m, 33H), 1.73-1.65( m, 23H), 1.65-1.50(m, 45H), 1.52(d, J=5.6Hz, 2H), 1.34-1.30(m, 19H), 1.28(s, 11H), 0.99-0.93(m, 32H).

[0109] Example 34. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A34) 1 H NMR (500 MHz, chloroform) δ 8.35 (s, 1H), 7.62 (s, 1H), 7.39 (s, 1H), 7.05 (s, 1H), 6.43 (s, 1H), 5.97 (s, 1H), 5.59 (s, 1H), 5.50 (d, J = 15.7 Hz, 2H), 4.67 (s, 1H), 3.24 (d, J = 17.3 Hz, 2H), 2.48 (s, 1H), 2.08-2.04(m, 2H), 1.87(t, J=9.6Hz, 3H), 1.78(s, 1H), 1.72(dd, J=8.3 , 4.2Hz, 4H), 1.67(s, 1H), 1.65-1.50(m, 6H), 1.45(s, 1H), 1.36-1.28(m, 10H).

[0110] Example 35. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A35) 1 H NMR (500 MHz, chloroform) δ 8.51 (s, 1H), 8.33 (s, 1H), 8.28 (s, 1H), 7.42 (s, 1H), 7.07 (s, 1H), 6.66 (s, 1H), 6.41 (s, 1H), 5.86 (s, 1H), 5.04 (s, 1H), 4.52 (s, 1H), 3.32 (s, 1H), 3.24 (d, J = 16.6 Hz, 2H), 2.97 (s, 1H ), 2.16-2.01(m, 5H), 2.01-1.92(m, 2H), 1.82(s, 1H), 1.78-1.69(m, 8H), 1.65(d, J=15.4H z, 2H), 1.56-1.46(m, 3H), 1.44-1.40(m, 4H), 1.32(s, 1H), 1.17(s, 1H), 1.07-1.00(m, 2H).

[0111] Example 36. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A36) 1H NMR (500 MHz, chloroform) δ 8.98 (s, 1H), 8.03 (d, J = 1.1 Hz, 2H), 7.63 (d, J = 5.1 Hz, 2H), 7.37-7.27 (m, 4H), 7.21 (s, 1H), 6.95 (s, 1H), 6.43 (s, 1H), 6.01 (s, 1H), 4.94 (s, 1H), 4.85 (s, 1H), 4.67 (s, 1H), 4.41 (s, 1H), 4.3 2(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 2.77(s, 1H), 2.19(s, 1H), 2.13-2.01(m, 2H), 1.89(s, 1H) , 1.83-1.74(m, 2H), 1.74-1.69(m, 2H), 1.66(d, J=5.7Hz, 2H), 1.58-1.49(m, 6H), 1.31(s, 1H).

[0112] Example 37. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A37) 1 H NMR (500 MHz, chloroform) δ 9.39 (s, 1H), 8.47 (s, 1H), 8.11 (s, 1H), 7.62 (d, J = 3.2 Hz, 2H), 6.17 (d, J = 6.0 Hz, 2H), 5.59 (s, 1H), 5.27 (s, 1H), 4.98 (s, 1H), 4.91 (s, 1H), 3.45 (s, 1H), 3.35 (s, 1H), 2.51(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.98-1.95(m, 2H), 1.92(s, 1H) ), 1.73-1.61(m, 5H), 1.41-1.37(m, 2H), 1.34-1.28(m, 10H), 1.21-1.11(m, 3H).

[0113] Example 38. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A38) 1 H NMR (500 MHz, chloroform) δ 9.09 (s, 1H), 8.31 (s, 1H), 8.03 (d, J = 4.8 Hz, 2H), 7.61 (d, J = 2.2 Hz, 2H), 6.41 (s, 1H), 6.06 (s, 1H), 5.27 (s, 1H), 5.20 (s, 1H), 4.45 (s, 1H), 3.72 (s, 1H), 3. 45(s, 1H), 3.35(s, 1H), 2.73(s, 1H), 2.39-2.31(m, 2H), 2.19(s, 1H), 2.09-2 .05(m, 2H), 1.92(s, 1H), 1.76-1.56(m, 15H), 1.55-1.45(m, 6H), 1.30(s, 1H).

[0114] Example 39. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A39) 1 H NMR (500 MHz, chloroform) δ 9.55 (s, 1H), 9.32 (s, 1H), 8.12 (s, 1H), 7.96 (s, 1H), 7.64 (d, J = 11.6 Hz, 2H), 7.29-7.22 (m, 4H), 7.19 (s, 1H), 6.56 (s, 1H), 6.06 (s, 1H), 5.63 (s, 1H), 5.02 (s, 1H), 4.71 (s, 1H), 4.41 (s, 1H), 4.31 (s, 1H). H), 3.24(d, J=17.3Hz, 2H), 2.37(s, 1H), 2.10-2.02(m, 2H), 2.02-1.96(m, 3H), 1.82(s, 1H), 1.72(t , J=9.8Hz, 3H), 1.69-1.57(m, 3H), 1.53(s, 1H), 1.38-1.34(m, 2H), 1.31(s, 1H), 1.13-1.04(m, 3H).

[0115] Example 40. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A40) 1 H NMR (500MHz, chloroform)δ 9.29(s, 1H), 8.16(s, 1H), 8.11(s, 1H), 7.65(d, J=4.6Hz, 2H), 7.22(s, 1H), 5.87 (d, J=8.3Hz, 2H), 5.65(s, 1H), 4.94(s, 1H), 4.46(s, 1H), 3.24(d, J=14.8Hz, 2H) , 2.72(s, 1H), 2.11-2.01(m, 2H), 1.79(d, J=1.0Hz, 2H), 1.76-1.62(m, 5H), 1.59 (s, 1H), 1.49-1.42(m, 4H), 1.35-1.28(m, 11H), 1.25(s, 1H), 1.21-1.15(m, 2H).

[0116] Example 41. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A41) 1 H NMR (500MHz, chloroform)δ 9.64(s, 4H), 8.11(d, J=10.4Hz, 8H), 7.65(d, J=1.9Hz, 8H), 6.00(s, 4H), 5.76(s, 4H), 5.70(s, 4H), 5.64(s, 4H), 5.04(s, 4H), 4.45(s, 4H), 3.86(s, 4H), 3.24(d, J=17.3Hz, 8H), 2.85(s, 4H), 2.11-2.01(m, 9H), 1.99-1.91(m, 12H), 1.91-1.80(m, 9H), 1.75(s, 2H), 1.75-1.53(m, 62H), 1. 55-1.53(m, 1H), 1.51(s, 3H), 1.38-1.34(m, 7H), 1.30(s, 4H), 1.06(s, 3H), 1.03-0.99(m, 8H).

[0117] Example 42. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A42) 1 H NMR (500 MHz, chloroform) δ 8.56 (s, 1H), 8.19 (s, 1H), 7.82 (s, 1H), 7.58 (s, 1H), 7.42 (s, 1H), 7.42-7.28 (m, 5H), 7.21 (s, 1H), 6.00 (d, J = 2.7 Hz, 2H), 4.43 (s, 1H), 4.33 (s, 1H), 4.11 (s, 1H), 3.83 (d, J = 3.7 Hz, 2H), 3.45(s, 1H), 3.35(s, 1H), 3.25(s, 1H), 2.15(s, 1H), 2.09-2.05(m, 2H), 1.91(s, 1H), 1.73-1.69(m, 2H), 1.62-1.55(m, 3H), 1.36-1.27(m, 6H), 1.23(s, 1H), 1.20-1.14(m, 2H).

[0118] Example 43. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A43) 1 H NMR (500 MHz, chloroform) δ 9.34 (s, 1H), 8.46 (s, 1H), 8.17 (s, 1H), 7.82 (s, 1H), 7.72 (s, 1H), 7.55 (s, 1H), 7.50 (s, 1H), 5.96 (s, 1H), 5.84 (s, 1H), 5.40 (s, 1H), 5.22 (s, 1H), 4.77 (s, 1H), 3.45 (s, 1H) , 3.35(s, 1H), 2.83(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.94-1.81(m, 3H), 1.73- 1.63(m, 5H), 1.40-1.36(m, 2H), 1.36-1.27(m, 10H), 1.18(s, 1H), 1.14-1.10(m, 2H).

[0119] Example 44. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A44) 1 H NMR (500 MHz, chloroform) δ 8.47 (s, 1H), 8.24 (s, 1H), 8.06 (s, 1H), 7.73 (s, 1H), 7.65 (s, 1H), 7.43 (d, J = 13.7 Hz, 2H), 6.58 (s, 1H), 6.06 (s, 1H), 5.40 (s, 1H), 5.20 (s, 1H), 4.45 (s, 1H), 3.73 (s , 1H), 3.45(s, 1H), 3.35(s, 1H), 2.72(s, 1H), 2.34-2.30(m, 2H), 2.19(s, 1H), 2.0 9-2.05(m, 2H), 1.92(s, 1H), 1.77-1.56(m, 15H), 1.55-1.46(m, 6H), 1.30(s, 1H).

[0120] Example 45. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A45) 1H NMR (500MHz, chloroform) δ 8.42(s, 1H), 8.15(s, 1H), 7.79(s, 1H), 7.69(s, 1H), 7.47(s, 1H), 7.42(s, 1H), 7.34-7.25(m, 4H), 7.20(s, 1H), 6.77(s, 1H), 5.89(s, 1H), 5.82(s, 1H), 5.57(d, J=7.5Hz, 2H), 4.42(d, J=5.7Hz, 2H), 4.34(s, 1H), 3.24(d, J=19.0Hz, 2H), 2.81(s, 1H), 2.43(s, 1H), 2.11-2.01(m, 2H), 1.95(s, 1H), 1.86(s, 1H), 1.81-1. 74(m, 3H), 1.69(dt, J=17.1, 8.6Hz, 5H), 1.47(s, 1H), 1.41-1.37(m, 2H), 1.31(s, 1H), 0.84-0.77(m, 2H).

[0121] Example 46. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A46) 1 H NMR (500 MHz, chloroform) δ 8.46 (s, 3H), 8.13 (s, 3H), 7.79 (s, 3H), 7.69 (d, J = 0.8 Hz, 6H), 7.44 (d, J = 32.8 Hz, 6H), 6.55 (s, 3H), 6.05 (s, 3H), 5.75 (s, 3H), 4.77 (d, J = 2.1 Hz, 6H), 3.25 (s, 3H) , 3.21(s, 3H), 2.70(s, 3H), 2.11-2.01(m, 6H), 1.96-1.87(m, 6H), 1.79(d, J=13. 1Hz, 5H), 1.70(dt, J=19.3, 3.5Hz, 19H), 1.60-1.51(m, 18H), 1.35-1.30(m, 30H).

[0122] Example 47. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A47) 1 H NMR (500MHz, chloroform)δ 9.06(s, 3H), 8.44(s, 3H), 8.15(s, 3H), 7.79(s, 3H), 7.75(s, 3H), 7.70(s, 3H), 7.48(d, J=8.2Hz, 6H), 7.3 8(s, 3H), 5.73(s, 3H), 4.96(s, 3H), 4.57(s, 3H), 3.90(s, 3H), 3.24(d, J=14.7Hz, 6H), 2.92(s, 3H), 2.15- 2.11(m, 5H), 2.11-2.01(m, 9H), 1.99(t, J=7.9Hz, 7H), 1.80(s, 2H), 1.76-1.65(m, 18H), 1.65-1.58(m, 24 H), 1.45(t, J=13.5Hz, 10H), 1.36(dd, J=21.5, 15.7Hz, 2H), 1.33(s, 3H), 1.20(s, 2H), 1.11-1.04(m, 6H).

[0123] Example 48. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-2-carboxamide (A48) 1H NMR (500 MHz, chloroform) δ 8.36 (s, 1H), 7.55 (d, J = 12.3 Hz, 2H), 7.34 (t, J = 21.8 Hz, 3H), 7.30-7.17 (m, 9H), 7.15 (d, J = 2.2 Hz, 2H), 7.09 (s, 1H), 6.35 (s, 1H), 6.01 (s, 1H), 5.67 (s, 1H), 5. 03(s, 1H), 4.88(s, 1H), 4.37(s, 1H), 4.30(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3. 15(d, J=18.6Hz, 2H), 2.94(s, 1H), 2.19(s, 1H), 2.10-2.04(m, 2H), 1.92(s, 1H).

[0124] Example 49. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-2-carboxamide (A49) 1 H NMR (500 MHz, chloroform) δ 8.26 (s, 1H), 7.46 (s, 1H), 7.32 (t, J = 17.0 Hz, 3H), 7.20 (dd, J = 7.8, 5.2 Hz, 4H), 7.12 (s, 1H), 7.06 (s, 1H), 6.01 (s, 1H), 5.57 (s, 1H), 4.84 (s, 1H), 4.69 (s, 1H) , 4.53(s, 1H), 3.45(s, 1H), 3.41(s, 1H), 3.35(s, 1H), 3.30(s, 1H), 3.19(s, 1H) , 2.96(s, 1H), 2.16(s, 1H), 2.13-2.01(m, 2H), 1.89(s, 1H), 1.30-1.26(m, 9H).

[0125] Example 50. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-2-carboxamide (A50) 1H NMR (500 MHz, chloroform) δ 8.35 (s, 1H), 7.90 (s, 1H), 7.52 (d, J = 25.5 Hz, 2H), 7.39 (s, 1H), 7.29-7.21 (m, 4H), 7.14 (d, J = 3.6 Hz, 2H), 7.08 (s, 1H), 6.52 (s, 1H), 6.16 (s, 1H), 5.70 (s, 1H), 4.92 (s, 1H), 4.78 (s, 1H), 3.46 (d, J=5.2Hz, 2H), 3.35(s, 1H), 3.21(s, 1H), 2.85(d, J=4.0Hz, 2H), 2.17(s, 1H), 2.13-2.02(m, 2H), 2.00-1.90(m, 3H), 1.68(s, 1H), 1.56-1.50(m, 2H), 1.49-1.45(m, 3H), 1.44-1.40(m, 2H).

[0126] Example 51. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-2-carboxamide (A51) 1 H NMR (500 MHz, chloroform) δ 8.70 (s, 1H), 7.50 (s, 1H), 7.39-7.20 (m, 5H), 7.20-7.11 (m, 4H), 7.09 (d, J = 4.4 Hz, 2H), 7.06-6.94 (m, 2H), 6.90 (s, 1H), 6.19 (s, 1H), 5.93 (s, 1H), 5.51 (s, 1H), 4.7 0(s, 1H), 4.25(d, J=17.1Hz, 2H), 3.79(d, J=9.5Hz, 2H), 3.24(t, J=8.3Hz, 3H), 3. 04(s, 1H), 2.16(s, 1H), 2.12-2.04(m, 3H), 1.78(s, 1H), 1.72(s, 1H), 1.62(s, 1H).

[0127] Example 52. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-2-carboxamide (A52) 1 H NMR (500MHz, chloroform)δ 8.64(d, J=17.0Hz, 2H), 8.19(s, 1H), 7.56(s, 1H), 7.43(s, 1H), 7.36-7.27(m, 2H), 7. 27-7.22(m, 2H), 7.14(d, J=12.9Hz, 2H), 7.08(s, 1H), 5.63(s, 1H), 5.01(d, J=14.2Hz, 2H), 4.78(d, J=1.3Hz, 2H), 3.24(d, J=18.2Hz, 2H), 3.18(s, 1H), 3.03(s, 1H), 2.97(s, 1H), 2.06(t, J=3.5Hz, 3H), 1.94(s, 1H), 1.88(s, 1H), 1.81(s, 1H), 1.21-1.17(m, 9H).

[0128] Example 53. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-2-carboxamide (A53) 1 H NMR (500MHz, chloroform)δ 8.76(s, 1H), 7.53(s, 1H), 7.41(d, J=25.5Hz, 2H), 7.27-7.21(m, 2H), 7.21-7.18(m, 2H), 7.15(d, J=7 .6Hz, 2H), 7.08(s, 1H), 5.95(s, 1H), 5.61(s, 1H), 5.25(s, 1H), 5.14(s, 1H), 4.78(s, 1H), 3.42(s, 1H) , 3.25(t, J=12.6Hz, 3H), 2.87(s, 1H), 2.70(s, 1H), 2.56(s, 1H), 2.08-2.04(m, 2H), 2.02-1.90(m, 2H) , 1.87(s, 1H), 1.80(s, 1H), 1.68(d, J=3.3Hz, 2H), 1.55-1.51(m, 4H), 1.48(s, 1H), 1.45-1.39(m, 2H).

[0129] Example 54. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzofuran-2-carboxamide (A54) 1 H NMR (500 MHz, chloroform) δ 7.51 (d, J = 8.2 Hz, 2H), 7.41 (s, 1H), 7.30-7.12 (m, 12H), 6.67 (s, 1H), 5.69-5.61 (m, 3H), 5.09 (s, 1H), 4.88 (s, 1H), 4.41 (s, 1H), 4.33 (s, 1H), 3.45 (s, 1H), 3.35 (s, 1H), 3.26 (s, 1H), 3.16 (s, 1H), 3.07 (s, 1H), 2.19 (s, 1H), 2.09-2.05 (m, 2H), 1.92 (s, 1H).

[0130] Example 55. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzofuran-2-carboxamide (A55) 1 H NMR (500MHz, chloroform) δ 7.54(s, 1H), 7.47(d, J=17.7Hz, 2H), 7.28-7.22(m, 3H), 7.18(dd, J=20.8 , 5.2Hz, 4H), 6.42(s, 1H), 6.05(s, 1H), 5.83(s, 1H), 5.27(s, 1H), 4.98(s, 1H), 4.85(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.19(s, 1H), 2.96(s, 1H), 2.6 1(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.93(s, 1H), 1.34-1.30(m, 9H).

[0131] Example 56. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzofuran-2-carboxamide (A56) 1 H NMR (500MHz, chloroform)δ 8.77(s, 2H), 8.67(s, 2H), 7.56(s, 1H), 7.50(s, 3H), 7.41(s, 2H), 7.28-7.19(m, 6H), 7. 16(d, J=4.9Hz, 4H), 7.13-7.04(m, 4H), 6.04(s, 2H), 5.93(s, 2H), 5.05(s, 2H), 4.66(s, 2H), 3.70(s, 2H), 3.45(s, 2H), 3.35(s, 1H), 3.25(s, 2H), 3.05(s, 2H), 2.88(s, 2H), 2.1 9(s, 2H), 2.09-2.05(m, 4H), 1.97-1.91(m, 5H), 1.68-1.64(m, 3H), 1.64-1.43(m, 13H).

[0132] Example 57. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzofuran-2-carboxamide (A57) 1 H NMR (500 MHz, chloroform) δ 7.48 (s, 1H), 7.29 (d, J = 38.0 Hz, 2H), 7.25 (s, 1H), 7.27-7.19 (m, 3H), 7.19-7.05 (m, 10H), 6.97 (s, 1H), 6.43 (s, 1H), 6.07 (s, 1H), 5.18 (d, J = 3.4 Hz, 2H), 4.73 (s, 1H), 4.6 3(s, 1H), 4.36(s, 1H), 4.29(s, 1H), 3.24(d, J=16.8Hz, 2H), 3.10(s, 1H), 2.86(d, J= 21.8Hz, 2H), 2.43(s, 1H), 2.08-2.04(m, 2H), 1.85(s, 1H), 1.79(s, 1H), 1.64(s, 1H).

[0133] Example 58. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzofuran-2-carboxamide (A58) 1 H NMR (500MHz, chloroform) δ 9.35(s, 5H), 7.60(s, 5H), 7.48(d, J=29.1Hz, 10H), 7.28-7.18(m, 27H) , 7.16(d, J=17.5Hz, 8H), 5.86(s, 5H), 5.55(s, 5H), 4.94(s, 5H), 4.69(s , 5H), 3.24(t, J=10.0Hz, 14H), 2.90(s, 5H), 2.66(s, 5H), 2.09-2.02(m, 10H), 1.92(s, 4H), 1.84-1.80(m, 8H), 1.76(s, 4H), 1.30-1.26(m, 44H).

[0134] Example 59. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzofuran-2-carboxamide (A59) 1 H NMR (500MHz, chloroform) δ 9.35(s, 5H), 7.60(s, 5H), 7.48(d, J=29.1Hz, 10H), 7.28-7.18(m, 27H) , 7.16(d, J=17.5Hz, 8H), 5.86(s, 5H), 5.55(s, 5H), 4.94(s, 5H), 4.69(s , 5H), 3.24(t, J=10.0Hz, 14H), 2.90(s, 5H), 2.66(s, 5H), 2.09-2.02(m, 10H), 1.92(s, 4H), 1.84-1.80(m, 8H), 1.76(s, 4H), 1.30-1.26(m, 44H).

[0135] Example 60. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzothiophene-2-carboxamide (A60) 1 H NMR (500 MHz, chloroform) δ 8.40 (s, 1H), 7.91 (s, 1H), 7.76 (s, 1H), 7.33 (d, J = 3.7 Hz, 2H), 7.32-7.16 (m, 10H), 7.13 (d, J = 16.7 Hz, 2H), 6.27 (s, 1H), 5.97 (s, 1H), 5.64 (s, 1H), 5.0 3(s, 1H), 4.89(s, 1H), 4.34(d, J=4.2Hz, 2H), 3.45(s, 1H), 3.35(s, 1H), 3. 15-3.11(m, 2H), 2.94(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H).

[0136] Example 61. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzothiophene-2-carboxamide (A61) 1 H NMR (500MHz, chloroform) δ 8.93(s, 1H), 7.82(d, J=4.4Hz, 2H), 7.28(dd, J=20.7, 7.2Hz, 4H), 7.22-7 .11(m, 3H), 6.05(s, 1H), 4.70(s, 1H), 4.64(s, 1H), 4.59(s, 1H), 4.39(s, 1 H), 3.99(s, 1H), 3.55(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.15(s, 1H), 2.9 5(s, 1H), 2.17(s, 1H), 2.13-2.02(m, 2H), 1.89(s, 1H), 1.21-1.17(m, 9H).

[0137] Example 62. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzothiophene-2-carboxamide (A62) 1 H NMR (500 MHz, chloroform) δ 8.73 (s, 1H), 8.54 (s, 1H), 8.35 (s, 1H), 7.91 (s, 1H), 7.74 (s, 1H), 7.32 (d, J = 1.5 Hz, 2H), 7.28-7.23 (m, 2H), 7.15 (s, 1H), 7.12-7.05 (m, 2H), 6.14 (s, 1H), 5.94 (s, 1H), 5.04 (s, 1H), 4.66 (s, 1H), 3. 45(d, J=3.2Hz, 2H), 3.35(s, 1H), 3.26(s, 1H), 3.05(s, 1H), 2.89(s, 1H), 2.19(s, 1H), 2.09-2.05 (m, 2H), 1.95-1.91(m, 3H), 1.73-1.64(m, 3H), 1.56-1.52(m, 2H), 1.50(s, 1H), 1.46-1.40(m, 2H).

[0138] Example 63. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzothiophene-2-carboxamide (A63) 1 H NMR (500 MHz, chloroform) δ 8.49 (s, 1H), 8.30 (s, 1H), 8.00 (s, 1H), 7.63 (s, 1H), 7.29 (dd, J = 19.0, 2.9 Hz, 4H), 7.18-7.07 (m, 5H), 7.07-6.97 (m, 3H), 6.33 (s, 1H), 6.11 (s, 1H), 4.93-4.89 ( m, 2H), 4.36(d, J=9.1Hz, 2H), 4.29(s, 1H), 3.28-3.20(m, 3H), 2.92(s, 1H), 2.58 (s, 1H), 2.16(s, 1H), 2.08-2.04(m, 2H), 1.83(s, 1H), 1.77(s, 1H), 1.73(s, 1H).

[0139] Example 64. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzothiophene-2-carboxamide (A64) 1 H NMR (500 MHz, chloroform) δ 8.38 (s, 1H), 7.90 (s, 1H), 7.75 (s, 1H), 7.30 (dd, J = 17.5, 1.0 Hz, 4H), 7.26-7.19 (m, 2H), 7.17 (s, 1H), 7.02 (s, 1H), 6.45 (s, 1H), 6.10 (s, 1H), 5.93 (s, 1H), 4.9 3(s, 1H), 4.86(s, 1H), 3.27-3.11(m, 3H), 2.95(s, 1H), 2.83(s, 1H), 2.11-2.01 (m, 2H), 1.95(s, 1H), 1.83(s, 1H), 1.76(s, 1H), 1.56(s, 1H), 1.35-1.31(m, 9H).

[0140] Example 65. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-benzothiophene-2-carboxamide (A65) 1 H NMR (500 MHz, chloroform) δ 8.28 (s, 6H), 7.86 (s, 6H), 7.60 (s, 6H), 7.27 (dd, J = 17.2, 1.6 Hz, 20H), 7.24-7.12 (m, 22H), 5.78 (s, 6H), 5.41 (s, 6H), 5.09 (s, 6H), 4.97 (s, 6H), 4.85 (s, 6H), 3.31-3.10 (m, 30H), 2.97(s, 6H), 2.60(s, 4H), 2.51(s, 5H), 2.12-2.00(m, 12H), 1.97-1.86(m, 12H), 1.71(t, J=16.5Hz, 17H), 1.58-1.45(m, 30H), 1.45-1.36(m, 12H), 1.12(s, 4H).

[0141] Example 66. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A66) 1 H NMR (500MHz, chloroform) δ 8.78(s, 1H), 7.69(s, 1H), 7.49(s, 1H), 7.34-7.13(m, 12H), 7.13-7.05 (m, 2H), 6.10(s, 1H), 5.99(s, 1H), 5.07(s, 1H), 4.69(s, 1H), 4.36(d, J= 3.5Hz, 2H), 3.78-3.74(m, 3H), 3.45(s, 1H), 3.35(s, 1H), 3.24(s, 1H), 3.06(s, 1H), 2.88(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.93(s, 1H).

[0142] Example 67. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A67) 1 H NMR (500 MHz, chloroform) δ 7.38 (s, 1H), 7.29-7.13 (m, 9H), 6.07 (s, 1H), 5.82 (d, J = 4.8 Hz, 2H), 5.28 (s, 1H), 4.94 (s, 1H), 4.87 (s, 1H), 3.67-3.63 (m, 3H), 3.45 (s, 1H), 3.35 (s, 1H), 3.19 (s, 1H), 2.93 (s, 1H), 2.68 (s, 1H), 2.18 (s, 1H), 2.09-2.05 (m, 2H), 1.94 (s, 1H), 1.34-1.30 (m, 9H).

[0143] Example 68. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A68) 1 H NMR (500MHz, chloroform)δ 7.49(s, 3H), 7.34-7.20(m, 23H), 7.20(s, 3H), 7.15(s, 2H), 6.73(s, 3H), 6.27 (s, 3H), 5.73(s, 3H), 5.11(s, 3H), 4.83(s, 3H), 3.98(s, 2H), 3.76(s, 3H), 3.58 -3.54(m, 9H), 3.35(s, 2H), 3.22(s, 3H), 2.88(s, 3H), 2.63(s, 3H), 2.19(s, 2H) , 2.09-2.05(m, 6H), 1.95-1.91(m, 7H), 1.76-1.66(m, 7H), 1.66-1.55(m, 20H).

[0144] Example 69. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A69) 1 H NMR (500 MHz, chloroform) δ 7.35-7.29 (m, 2H), 7.29-7.26 (m, 1H), 7.26-7.06 (m, 11H), 6.67 (s, 1H), 6.05 (d, J = 11.7 Hz, 2H), 5.74 (s, 1H), 4.95 (s, 1H), 4.77 (s, 1H), 4.39 (s, 1H), 4.34 (s , 1H), 3.86-3.82(m, 3H), 3.29-3.17(m, 3H), 2.95(s, 1H), 2.56(s, 1H), 2.44(s , 1H), 2.12-2.00(m, 2H), 1.85(s, 1H), 1.78(s, 1H), 1.41(s, 1H), 1.15(s, 1H).

[0145] Example 70. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A70) 1 H NMR (500 MHz, chloroform) δ 7.51 (s, 1H), 7.31 (s, 1H), 7.22 (ddd, J = 42.8, 13.4, 8.7 Hz, 8H), 6.91 (s, 1H), 6.06 (s, 1H), 5.93 (s, 1H), 5.54 (s, 1H), 4.80 (s, 1H), 4.71 (s, 1H), 3.73-3 .69(m, 3H), 3.26(t, J=14.0Hz, 3H), 2.82(d, J=27.3Hz, 2H), 2.11-2.01(m, 2 H), 1.92(s, 1H), 1.82(s, 1H), 1.75(s, 1H), 1.54(s, 1H), 1.32-1.28(m, 9H).

[0146] Example 71. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-indole-2-carboxamide (A71) 1 H NMR (500 MHz, chloroform) δ 8.25 (s, 1H), 7.38 (s, 1H), 7.28 (dd, J = 15.9, 3.4 Hz, 4H), 7.24-7.12 (m, 5H), 5.93 (s, 1H), 5.32 (s, 1H), 5.07 (s, 1H), 4.75 (s, 1H), 4.41 (s, 1H), 3.85-3.77 (m , 4H), 3.27-3.20(m, 3H), 3.04(s, 1H), 2.84(s, 1H), 2.49(s, 1H), 2.17-2.10( m, 2H), 2.10-2.02(m, 2H), 1.86-1.75(m, 6H), 1.65(s, 1H), 1.58-1.52(m, 4H).

[0147] Example 72. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A72) 1 H NMR (500 MHz, chloroform) δ 8.55 (s, 1H), 7.52 (s, 1H), 7.44 (s, 1H), 7.38 (s, 1H), 7.32-7.27 (m, 4H), 7.27-7.12 (m, 8H), 7.10 (s, 1H), 6.00 (s, 1H), 5.04 (s, 1H), 4.92 (s, 1H), 4.7 7(s, 1H), 4.38(s, 1H), 4.30(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.27(s, 1H) ), 3.12(s, 1H), 2.87(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H).

[0148] Example 73. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A73) 1 H NMR (500 MHz, chloroform) δ 8.55 (s, 1H), 8.14 (s, 1H), 7.52 (s, 1H), 7.44 (s, 1H), 7.28-7.22 (m, 2H), 7.22-7.11 (m, 3H), 7.09 (s, 1H), 6.01 (s, 1H), 5.55 (s, 1H), 5.12 (s, 1H), 4.74 ( s, 1H), 4.31(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.30(s, 1H), 3.08(s, 1H), 2. 92(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H), 1.39-1.35(m, 9H).

[0149] Example 74. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A74) 1 H NMR (500 MHz, chloroform) δ 8.85 (s, 1H), 8.44 (s, 1H), 8.39 (s, 1H), 7.58 (s, 1H), 7.42 (s, 1H), 7.28-7.23 (m, 2H), 7.15 (s, 1H), 7.12-7.06 (m, 3H), 6.10 (s, 1H), 5.94 (s, 1H), 5.03 (s, 1H), 4.66 (s, 1H), 3.45 (d, J = 5. 0Hz, 2H), 3.35(s, 1H), 3.27(s, 1H), 3.06(s, 1H), 2.90(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H) ), 1.95-1.91(m, 3H), 1.72-1.68(m, 3H), 1.56-1.52(m, 2H), 1.50(s, 1H), 1.46-1.41(m, 2H).

[0150] Example 75. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A75) 1H NMR (500MHz, chloroform)δ 8.67(s, 13H), 7.46(s, 13H), 7.30-7.24(m, 28H), 7.24-7.14(m, 80H), 7.12-7.00(m, 30H), 7. 00(s, 11H), 6.93(d, J=12.0Hz, 26H), 6.07(s, 13H), 4.91(s, 13H), 4.80(s, 13H), 4.36(s, 13H) , 4.31(s, 13H), 4.27(s, 13H), 4.04(s, 13H), 3.31(d, J=52.2Hz, 35H), 3.22(s, 5H), 3.01(s, 14 H), 2.86(s, 11H), 2.31(s, 9H), 2.08-2.04(m, 25H), 1.83(s, 12H), 1.77(s, 10H), 1.54(s, 9H).

[0151] Example 76. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A76) 1 H NMR (500 MHz, chloroform) δ 8.53 (s, 8H), 7.62 (s, 8H), 7.43 (s, 8H), 7.38 (s, 8H), 7.26-7.21 (m, 16H), 7.21-7.14 (m, 21H), 7.14-7.11 (m, 4H), 7.09 (s, 8H), 5.81 (s, 8H), 5.66 (s, 8H), 5.34 (s, 8H), 4.92(s, 8H), 4.75(s, 8H), 3.33-3.20(m, 24H), 2.87(s, 7H), 2.59(s, 7H), 2.08-2.0 4(m, 16H), 1.86(s, 6H), 1.80(s, 7H), 1.73(s, 6H), 1.48(s, 6H), 1.34-1.30(m, 72H).

[0152] Example 77. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A77) 1 H NMR (500 MHz, chloroform) δ 9.14 (s, 1H), 9.09 (s, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 7.33-7.27 (m, 2H), 7.27-7.14 (m, 3H), 7.10 (s, 1H), 6.82 (s, 1H), 5.96 (s, 1H), 5.80 (s, 1H), 4.98 (s, 1H), 4.82 (s, 1H), 3.3 5(s, 1H), 3.24(d, J=14.7Hz, 2H), 3.16(s, 1H), 2.96(s, 1H), 2.83(s, 1H), 2.16-2.04(m , 5H), 1.82(s, 1H), 1.75(dd, J=19.9, 8.6Hz, 4H), 1.59-1.49(m, 4H), 1.44-1.40(m, 2H).

[0153] Example 78. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoxaline-2-carboxamide (A78) 1 H NMR (500MHz, chloroform) δ 9.21(s, 1H), 8.80(s, 1H), 8.10(d, J=21.9Hz, 2H), 7.71(s, 1H), 7.63(d, J =6.0Hz, 2H), 7.30-7.11(m, 10H), 6.38(s, 1H), 5.97(s, 1H), 4.90(s, 1H), 4.69(s, 1H), 4.36(d, J=4.9Hz, 2H), 3.45(s, 1H), 3.35(s, 1H), 3.16(s, 1H) ), 2.95(s, 1H), 2.86(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.93(s, 1H).

[0154] Example 79. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoxaline-2-carboxamide (A79) 1 H NMR (500 MHz, chloroform) δ 9.43 (s, 1H), 9.01 (s, 1H), 8.10 (d, J = 11.8 Hz, 2H), 7.68-7.64 (m, 2H), 7.25-7.19 (m, 1H), 7.19-7.09 (m, 4H), 6.12 (s, 1H), 6.04 (s, 1H), 5.51 (s, 1H), 5. 09(s, 1H), 4.74(s, 1H), 3.45(s, 1H), 3.35(d, J=2.3Hz, 2H), 3.11(s, 1H), 2. 89(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H), 1.39-1.35(m, 9H).

[0155] Example 80. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoxaline-2-carboxamide (A80) 1 H NMR (500 MHz, chloroform) δ 9.46 (s, 1H), 8.10 (d, J = 1.3 Hz, 2H), 7.64 (d, J = 1.4 Hz, 2H), 7.29-7.21 (m, 4H), 7.15 (s, 1H), 6.17 (s, 1H), 5.60 (s, 1H), 5.41 (s, 1H), 5.16 (s, 1H), 4.42 (s, 1H), 3.77 (s, 1H) ), 3.45(s, 1H), 3.35(d, J=2.0Hz, 2H), 2.94(s, 1H), 2.49(s, 1H), 2.19(s, 1H), 2.09- 2.05(m, 2H), 1.93(s, 1H), 1.81-1.74(m, 6H), 1.74-1.70(m, 2H), 1.57-1.51(m, 2H).

[0156] Example 81. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoxaline-2-carboxamide (A81) 1 H NMR (500MHz, chloroform)δ 9.04(s, 1H), 8.07(d, J=5.3Hz, 2H), 7.62(d, J=0.9Hz, 2H), 7.30-7.20(m, 5H), 7.20- 7.12(m, 5H), 7.10(s, 1H), 6.69(s, 1H), 5.68(d, J=19.5Hz, 2H), 5.14(s, 1H), 5.08(s , 1H), 4.42(s, 1H), 4.34(s, 1H), 3.37(s, 1H), 3.24(d, J=17.2Hz, 2H), 2.95(s, 1H), 2 .15(s, 1H), 2.09-2.03(m, 2H), 1.76(s, 1H), 1.70(s, 1H), 1.63(s, 1H), 1.43(s, 1H).

[0157] Example 82. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoxaline-2-carboxamide (A82) 1 H NMR (500MHz, chloroform)δ 9.37(s, 1H), 8.11(d, J=1.9Hz, 2H), 7.64(d, J=1.0Hz, 2H), 7.32-7.26(m, 2H), 7.2 6-7.13(m, 3H), 6.08(s, 1H), 5.93(d, J=13.8Hz, 2H), 5.60(s, 1H), 4.97(s, 1H), 4.8 3(s, 1H), 3.24(d, J=16.7Hz, 2H), 3.18(s, 1H), 2.93(s, 1H), 2.70(s, 1H), 2.11-2. 01(m, 2H), 1.98(s, 1H), 1.78(s, 1H), 1.71(s, 1H), 1.42(s, 1H), 1.35-1.31(m, 9H).

[0158] Example 83. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoxaline-2-carboxamide (A83) 1 H NMR (500 MHz, chloroform) δ 9.67 (s, 6H), 8.12 (d, J = 8.3 Hz, 12H), 7.66 (d, J = 1.4 Hz, 12H), 7.26-7.16 (m, 25H), 7.14 (s, 6H), 6.12 (s, 6H), 5.79 (s, 6H), 5.56 (s, 6H), 5.33 (s, 6H), 5.10 (s, 6H), 4.95 (s , 6H), 3.84(s, 6H), 3.27(t, J=34.6Hz, 16H), 3.21(d, J=6.1Hz, 2H), 3.02(s, 6H), 2.8 3(s, 6H), 2.11-2.01(m, 13H), 2.01-1.94(m, 18H), 1.75(s, 4H), 1.71-1.55(m, 59H).

[0159] Example 84. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoline-2-carboxamide (A84) 1 H NMR (500 MHz, chloroform) δ 8.46 (s, 1H), 8.12 (s, 1H), 7.78 (s, 1H), 7.65 (s, 1H), 7.54 (s, 1H), 7.44 (s, 1H), 7.31-7.24 (m, 4H), 7.24-7.14 (m, 4H), 7.12 (s, 2H), 5.72 (s, 1H), 5.54 (s, 1H), 5.14 (s, 1H), 4.70(s, 1H), 4.59(s, 1H), 4.29(d, J=9.5Hz, 2H), 3.74(s, 1H), 3.35(s, 1H), 3. 31(s, 1H), 3.08(s, 1H), 2.72(s, 1H), 2.17(s, 1H), 2.10-2.05(m, 2H), 1.89(s, 1H).

[0160] Example 85. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoline-2-carboxamide (A85) 1 H NMR (500 MHz, chloroform) δ 8.40 (d, J = 39.3 Hz, 11H), 8.36-8.34 (m, 1H), 8.19 (s, 6H), 7.80 (s, 6H), 7.71 (s, 6H), 7.49 (d, J = 5.7 Hz, 12H), 7.30-7.25 (m, 12H), 7.25-7.15 (m, 14H), 7.14 (s, 4H), 6.20 (s, 6H), 5.92 (s, 6H), 5.07(s, 6H), 4.75(s, 6H), 3.45(s, 6H), 3.38(d, J=25.1Hz, 12H), 3.32(s, 1H), 3.0 2(s, 6H), 2.35(s, 5H), 2.19(s, 4H), 2.09-2.05(m, 12H), 1.92(s, 5H), 1.36-1.32(m, 53H).

[0161] Example 86. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoline-2-carboxamide (A86) 1 H NMR (500 MHz, chloroform) δ 8.46 (s, 1H), 8.12 (s, 1H), 7.81 (s, 1H), 7.69 (s, 1H), 7.49 (d, J = 7.1 Hz, 2H), 7.26-7.20 (m, 2H), 7.20-7.09 (m, 3H), 5.94 (d, J = 1.5 Hz, 2H), 5.63 (s, 1H), 5.44 (s, 1H), 4 .91(s, 1H), 4.76(s, 1H), 3.89(s, 1H), 3.45(s, 1H), 3.34(d, J=11.1Hz, 2H), 3.01( s, 1H), 2.19(d, J=10.9Hz, 2H), 2.14-2.04(m, 4H), 1.92(s, 1H), 1.65-1.49(m, 8H).

[0162] Example 87. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoline-2-carboxamide (A87) 1 H NMR (500 MHz, chloroform) δ 8.46 (s, 1H), 8.10 (s, 1H), 7.78 (s, 1H), 7.66 (s, 1H), 7.55 (s, 1H), 7.45 (s, 1H), 7.26-7.11 (m, 10H), 6.86 (s, 1H), 5.98 (s, 1H), 5.89 (s, 1H), 5.56 (d, J = 16.8 Hz, 2H), 4.75 ( s, 1H), 4.44(s, 1H), 4.32(s, 1H), 3.44(s, 1H), 3.23(d, J=18.1Hz, 2H), 2.84(s, 1H), 2.72(s, 1H), 2.11-2.01(m, 2H), 1.98(s, 1H), 1.63(s, 1H), 1.56(s, 1H), 1.25(s, 1H).

[0163] Example 88. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoline-2-carboxamide (A88) 1 H NMR (500 MHz, chloroform) δ 8.50 (d, J = 13.8 Hz, 2H), 8.17 (s, 1H), 7.81 (s, 1H), 7.69 (s, 1H), 7.65 (s, 1H), 7.48 (s, 1H), 7.28-7.24 (m, 1H), 7.24-7.11 (m, 4H), 6.95 (s, 1H), 6.17 (s, 1H), 5.50 (s, 1H), 5.00 (s, 1H), 4.79(s, 1H), 3.24(d, J=15.4Hz, 2H), 3.08(s, 1H), 2.90(s, 1H), 2.69(s, 1H), 2 .11-2.01(m, 2H), 1.90(s, 1H), 1.84(d, J=3.8Hz, 2H), 1.78(s, 1H), 1.29-1.25(m, 9H).

[0164] Example 89. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-quinoline-2-carboxamide (A89) 1 H NMR (500MHz, chloroform)δ 9.70(s, 4H), 8.44(s, 4H), 8.18(s, 4H), 7.80(s, 4H), 7.69(d, J=18.4Hz, 8H), 7.48(d, J=4.0H z, 8H), 7.32-7.26(m, 8H), 7.23-7.13(m, 12H), 6.67(s, 4H), 5.84(s, 4H), 4.95(s, 4H), 4.88(s , 4H), 3.90(s, 4H), 3.31(d, J=56.1Hz, 10H), 3.22(s, 2H), 2.99(s, 4H), 2.86(s, 4H), 2.11-2.0 4(m, 8H), 2.01(t, J=7.0Hz, 12H), 1.81(s, 3H), 1.74(s, 3H), 1.67-1.60(m, 35H), 1.45(s, 3H).

[0165] Example 90. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-1H-indole-2-carboxamide (A90) 1 H NMR (500 MHz, chloroform) δ 8.36 (s, 1H), 7.52 (d, J = 19.2 Hz, 2H), 7.39 (s, 1H), 7.26-7.19 (m, 4H), 7.18 (s, 1H), 7.13 (s, 1H), 7.07 (s, 1H), 6.32 (s, 1H), 6.24 (s, 1H), 6.05 (s, 1H), 5.47 (s, 1H), 5.27 (s, 1H), 4. 61(s, 1H), 4.41(s, 1H), 4.32(s, 1H), 3.59(s, 1H), 3.45(s, 1H), 2.17(s, 1H), 2.09-2.05( m, 2H), 1.92(s, 1H), 1.73(d, J=11.4Hz, 2H), 1.63(s, 1H), 1.55(s, 1H), 1.12-0.99(m, 6H).

[0166] Example 91. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1H-indole-2-carboxamide (A91) 1 H NMR (500 MHz, chloroform) δ 9.33 (s, 1H), 8.28 (s, 1H), 7.46 (d, J = 15.1 Hz, 2H), 7.35 (s, 1H), 7.10 (s, 1H), 7.03 (s, 1H), 6.79 (s, 1H), 6.12 (s, 1H), 5.28 (s, 1H), 4.95 (s, 1H), 4.31 (s, 1H), 3. 45(s, 1H), 3.35(s, 1H), 2.75(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1) H), 1.70(d, J=19.2Hz, 2H), 1.44(s, 1H), 1.36-1.32(m, 9H), 0.99-0.85(m, 6H).

[0167] Example 92. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1H-indole-2-carboxamide (A92) 1H NMR (500 MHz, chloroform) δ 8.38 (s, 1H), 7.51 (d, J = 17.6 Hz, 2H), 7.37 (s, 1H), 7.12 (s, 1H), 7.06 (s, 1H), 6.50 (s, 1H), 6.00 (s, 1H), 5.60 (s, 1H), 5.50 (s, 1H), 5.00 (s, 1H), 4.68 (s, 1H), 3.45 (s, 1H), 3.35 (s, 1H), 3. 29(s, 1H), 2.71(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.97-1.91(m, 3H), 1.70(t, J=9.1Hz , 3H), 1.59-1.55(m, 2H), 1.50(dd, J=10.4,1.1Hz, 4H), 1.43-1.38(m, 2H), 1.13-1.00(m, 6H).

[0168] Example 93. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-1H-indole-2-carboxamide (A93) 1 H NMR (500 MHz, chloroform) δ 8.63 (s, 1H), 7.56 (s, 1H), 7.46 (d, J = 25.5 Hz, 2H), 7.29-7.24 (m, 2H), 7.24-7.17 (m, 3H), 7.17-7.06 (m, 3H), 6.14 (s, 1H), 5.63 (s, 1H), 5.02 (d, J = 15.0 Hz, 2H), 4.43 (s, 1H), 4.3 7(s, 1H), 4.30(s, 1H), 3.24(d, J=17.4Hz, 2H), 2.81(s, 1H), 2.21(s, 1H), 2.08-2.04(m, 2H), 1.85(s, 1H), 1.77(t, J=13.2Hz, 3H), 1.51(s, 1H), 1.41(s, 1H), 1.04-0.90(m, 6H).

[0169] Example 94. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1H-indole-2-carboxamide (A94) 1 H NMR (500 MHz, chloroform) δ 8.38 (s, 1H), 8.13 (s, 1H), 7.49 (s, 1H), 7.41 (s, 1H), 7.37 (s, 1H), 7.12 (s, 1H), 7.04 (s, 1H), 5.95 (s, 1H), 5.30 (d, J = 18.0 Hz, 2H), 4.86 (s, 1H), 4.51 (s, 1H), 3.23 (d , J=15.7Hz, 2H), 2.45(s, 1H), 2.19(s, 1H), 2.08-2.04(m, 2H), 1.96(s, 1H), 1.75( s, 1H), 1.69(d, J=8.0Hz, 2H), 1.51(s, 1H), 1.36-1.27(m, 10H), 1.12-0.99(m, 6H).

[0170] Example 95. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1H-indole-2-carboxamide (A95) 1 H NMR (500 MHz, chloroform) δ 9.04 (s, 1H), 8.28 (s, 1H), 7.50 (d, J = 31.2 Hz, 2H), 7.38 (s, 1H), 7.13 (s, 1H), 7.06 (s, 1H), 6.19 (s, 1H), 5.81 (s, 1H), 5.63 (s, 1H), 4.78 (s, 1H), 4.59 (s, 1H), 3.94 (s, 1H), 3.06 ... .24(d, J=18.2Hz, 2H), 2.35(s, 1H), 2.13-2.04(m, 4H), 2.00(s, 1H), 1.83-1.60(m, 8H) ), 1.57(s, 1H), 1.52-1.46(m, 2H), 1.45-1.41(m, 2H), 1.33(s, 1H), 1.13-1.01(m, 6H).

[0171] Example 96. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-benzofuran-2-carboxamide (A96) 1 H NMR (500 MHz, chloroform) δ 7.74 (s, 1H), 7.42 (s, 1H), 7.36-7.26 (m, 4H), 7.23 (s, 1H), 7.17 (s, 1H), 7.07 (s, 1H), 6.96 (s, 1H), 6.46 (s, 1H), 6.22 (s, 1H), 5.75 (s, 1H), 5.06 (s, 1H), 4.63 (s, 1H), 4.46 (d, J=17.5Hz, 2H), 4.34(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.28(s, 1H), 2.19(s, 1H), 2.09 -2.05(m, 2H), 1.93(s, 1H), 1.67(s, 1H), 1.55(s, 1H), 1.19(s, 1H), 1.07-0.94(m, 6H).

[0172] Example 97. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-benzofuran-2-carboxamide (A97) 1 H NMR (500MHz, chloroform) δ 8.17(s, 1H), 7.45(d, J=28.3Hz, 2H), 7.22(s, 1H), 7.15(s, 1H), 6.41(s, 1 H), 6.00(s, 1H), 5.96(s, 1H), 4.94(s, 1H), 4.55(s, 1H), 3.45(s, 1H), 3.3 5(s, 1H), 2.53(s, 1H), 2.18(s, 1H), 2.13-2.02(m, 2H), 1.93(s, 1H), 1.76 (s, 1H), 1.65(s, 1H), 1.35-1.31(m, 9H), 1.25(s, 1H), 1.07-0.94(m, 6H).

[0173] Example 98. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-benzofuran-2-carboxamide (A98) 1H NMR (500MHz, chloroform)δ 7.59(s, 4H), 7.55-7.39(m, 12H), 7.22(s, 4H), 7.15(s, 4H), 6.04(s, 4H), 5.94(s, 4H), 5.89( s, 4H), 4.87(s, 4H), 4.48(s, 4H), 3.80(s, 4H), 3.45(s, 4H), 3.35(s, 3H), 2.58(s, 4H), 2.18(s , 4H), 2.11-2.04(m, 8H), 1.95-1.88(m, 19H), 1.87(t, J=3.1Hz, 4H), 1.75(d, J=29.9Hz, 6H), 1 .71(d, J=3.3Hz, 2H), 1.69-1.64(m, 8H), 1.62(s, 3H), 1.59-1.51(m, 8H), 1.06-0.93(m, 24H).

[0174] Example 99. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-benzofuran-2-carboxamide (A99) 1 H NMR (500 MHz, chloroform) δ 7.58 (s, 1H), 7.52 (d, J = 13.8 Hz, 2H), 7.38-7.32 (m, 2H), 7.30 (s, 1H), 7.26 (s, 1H), 7.23-7.16 (m, 3H), 6.21 (s, 1H), 5.77 (s, 1H), 5.68 (s, 1H), 4.86 (s, 1H), 4.82 (s, 1H), 4.56 (s, 1H), 4.37(s, 1H), 4.33(s, 1H), 3.24(d, J=17.0Hz, 2H), 2.63(s, 1H), 2.05(t, J=5.4Hz, 3H), 1.8 2(s, 1H), 1.75(s, 1H), 1.60(d, J=3.4Hz, 2H), 1.48(s, 1H), 1.39(s, 1H), 1.09-1.00(m, 6H).

[0175] Example 100. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-benzofuran-2-carboxamide (A100) 1 H NMR (500 MHz, chloroform) δ 7.58 (s, 1H), 7.52 (d, J = 13.8 Hz, 2H), 7.38-7.32 (m, 2H), 7.30 (s, 1H), 7.26 (s, 1H), 7.23-7.16 (m, 3H), 6.21 (s, 1H), 5.77 (s, 1H), 5.68 (s, 1H), 4.86 (s, 1H), 4.82 (s, 1H), 4.56 (s, 1H), 4.37(s, 1H), 4.33(s, 1H), 3.24(d, J=17.0Hz, 2H), 2.63(s, 1H), 2.05(t, J=5.4Hz, 3H), 1.8 2(s, 1H), 1.75(s, 1H), 1.60(d, J=3.4Hz, 2H), 1.48(s, 1H), 1.39(s, 1H), 1.09-1.00(m, 6H).

[0176] Example 101. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-benzofuran-2-carboxamide (A101) 1 H NMR (500MHz, chloroform)δ 7.59(s, 1H), 7.48(d, J=9.6Hz, 2H), 7.20(s, 1H), 7.14(s, 1H), 5.80(s, 1H), 5.26(s , 1H), 5.11(d, J=5.2Hz, 2H), 4.91(s, 1H), 3.81(s, 1H), 3.24(d, J=17.3Hz, 2H), 2.61 (s, 1H), 2.09-2.02(m, 4H), 1.95-1.87(m, 2H), 1.84(s, 1H), 1.77(s, 1H), 1.69(s, 1 H), 1.58(d, J=5.5Hz, 2H), 1.51-1.44(m, 4H), 1.26-1.22(m, 4H), 1.08-0.95(m, 6H).

[0177] Example 102. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-benzothiophene-2-carboxamide (A102) 1 H NMR (500 MHz, chloroform) δ 8.47 (s, 1H), 7.91 (s, 1H), 7.78 (s, 1H), 7.33 (d, J = 6.1 Hz, 2H), 7.28-7.17 (m, 5H), 6.42 (s, 1H), 6.05 (s, 1H), 5.73 (s, 1H), 5.38 (s, 1H), 5.27 (s, 1H), 4.46 (s, 1H), 4.3 6(d, J=16.9Hz, 2H), 3.45(s, 1H), 3.35(s, 1H), 2.67(s, 1H), 2.18(s, 1H), 2.09-2. 05(m, 2H), 1.92(s, 1H), 1.82(s, 1H), 1.70(s, 1H), 1.52(s, 1H), 1.10-0.96(m, 6H).

[0178] Example 103. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-benzothiophene-2-carboxamide (A103) 1 H NMR (500 MHz, chloroform) δ 8.37 (s, 1H), 7.89 (s, 1H), 7.73 (s, 1H), 7.30 (d, J = 2.2 Hz, 2H), 6.58 (s, 1H), 6.03 (s, 1H), 5.61 (s, 1H), 5.53 (s, 1H), 5.02 (s, 1H), 4.70 (s, 1H), 3.45 (s, 1H), 3.35(s, 1H), 2.69(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.93(s, 1H) , 1.69(d, J=8.4Hz, 2H), 1.49(s, 1H), 1.32-1.28(m, 9H), 1.10-1.02(m, 6H).

[0179] Example 104. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-benzothiophene-2-carboxamide (A104) 1 H NMR (500 MHz, chloroform) δ 8.63 (s, 1H), 7.91 (s, 1H), 7.74 (s, 1H), 7.34-7.30 (m, 2H), 6.18 (d, J = 11.5 Hz, 2H), 6.02 (s, 1H), 4.62 (s, 1H), 4.48 (s, 1H), 3.45 (s, 1H), 3.35 (s, 1H), 3.27 (s, 1H), 2.56 (s, 1H), 2.19(s, 1H), 2.11-2.05(m, 3H), 1.92(s, 1H), 1.83-1.70(m, 3H), 1.69(s, 1 H), 1.59-1.54(m, 3H), 1.50(t, J=6.7Hz, 3H), 1.42-1.37(m, 2H), 1.12-0.98(m, 6H).

[0180] Example 105. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-benzothiophene-2-carboxamide (A105) 1 H NMR (500 MHz, chloroform) δ 8.43 (s, 1H), 7.93 (d, J = 0.7 Hz, 2H), 7.74 (s, 1H), 7.33 (d, J = 2.2 Hz, 2H), 7.30-7.25 (m, 4H), 7.20 (s, 1H), 6.65 (s, 1H), 6.05 (s, 1H), 5.58 (s, 1H), 4.71 (s, 1H), 4.52 (s, 1H), 4.40 (s, 1H). H), 4.30(s, 1H), 3.23(d, J=15.8Hz, 2H), 2.73(s, 1H), 2.16(s, 1H), 2.08-2.04(m, 2H), 1.8 0(s, 1H), 1.69(d, J=6.6Hz, 2H), 1.63(s, 1H), 1.44(s, 1H), 1.35(s, 1H), 1.12-0.99(m, 6H).

[0181] Example 106. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-benzothiophene-2-carboxamide (A106) 1 H NMR (500 MHz, chloroform) δ 8.39 (s, 1H), 7.91 (s, 1H), 7.71 (s, 1H), 7.31 (d, J = 2.6 Hz, 2H), 6.50 (s, 1H), 5.87 (s, 1H), 5.71 (s, 1H), 5.57 (s, 1H), 4.80 (s, 1H), 4.75 (s, 1H), 3.23 (d, J = 15.7 Hz , 2H), 2.64(s, 1H), 2.08-2.04(m, 2H), 1.87(d, J=17.5Hz, 2H), 1.68(d, J=6.0Hz , 2H), 1.61(d, J=2.0Hz, 2H), 1.37(s, 1H), 1.32-1.28(m, 9H), 1.10-0.97(m, 6H).

[0182] Example 107. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-benzothiophene-2-carboxamide (A107) 1 H NMR (500 MHz, chloroform) δ 8.30 (s, 15H), 8.25 (s, 15H), 7.87 (s, 15H), 7.71 (s, 15H), 7.30 (d, J = 1.3 Hz, 30H), 6.03 (s, 15H), 5.58 (s, 15H), 5.39 (s, 15H), 5.03 (s, 15H), 4.37 (s, 15H), 3.85 (s, 15H), 3.24 (d, J =16.7Hz, 29H), 2.67(s, 11H), 2.57(s, 13H), 2.08-2.04(m, 30H), 1.96-1.90(m, 46H), 1.8 6(s, 15H), 1.79(s, 12H), 1.76-1.53(m, 169H), 1.58(d, J=5.6Hz, 3H), 1.05-0.92(m, 93H).

[0183] Example 108. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-1-methyl-1H-indole-2-carboxamide (A108) 1 H NMR (500MHz, chloroform)δ 7.39(d, J=5.1Hz, 10H), 7.31-7.22(m, 12H), 7.22-7.06(m, 35H), 5.99(s, 5H), 5.2 9(s, 5H), 4.40(d, J=4.6Hz, 10H), 4.30(d, J=5.3Hz, 1H), 4.24(d, J=52.5Hz, 9H), 3. 68-3.64(m, 15H), 3.58(s, 5H), 3.45(s, 5H), 2.78(s, 5H), 2.17(s, 3H), 2.15-1.95 (m, 17H), 1.89(s, 4H), 1.81(s, 5H), 1.62(s, 5H), 1.48(s, 4H), 1.07-0.94(m, 31H).

[0184] Example 109. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1-methyl-1H-indole-2-carboxamide (A109) 1 H NMR (500 MHz, chloroform) δ 8.20 (s, 1H), 7.48 (s, 1H), 7.27 (d, J = 17.1 Hz, 2H), 7.18 (d, J = 7.0 Hz, 2H), 6.13 (s, 1H), 5.90 (s, 1H), 5.38 (s, 1H), 5.08 (s, 1H), 4.65 (s, 1H), 3.79-3.75 (m, 3H), 3. 45(s, 1H), 3.35(s, 1H), 2.81(s, 1H), 2.17(s, 1H), 2.13-2.02(m, 2H), 1.93(s, 1H) ), 1.67(s, 1H), 1.60(s, 1H), 1.55(s, 1H), 1.34-1.30(m, 9H), 1.13-1.00(m, 6H).

[0185] Example 110. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1-methyl-1H-indole-2-carboxamide (A110) 1 H NMR (500MHz, chloroform)δ 7.37(s, 3H), 7.28(d, J=4.7Hz, 6H), 7.19(d, J=11.4Hz, 6H), 6.24(s, 3H), 5.90(s, 3H), 5.81(s, 3H), 5.30(s, 3H), 4.90(s, 3H), 4.68(s, 3H), 3.90-3.86(m, 9H), 3.45(s, 3H), 3.37-3.33(m, 5H) , 2.70(s, 3H), 2.19(s, 3H), 2.12-2.04(m, 6H), 1.93(s, 3H), 1.86-1.76(m, 9H), 1.71-1.60(m, 1 1H), 1.60-1.54(m, 1H), 1.51(dd, J=18.4, 1.5Hz, 11H), 1.44-1.38(m, 6H), 1.08-0.95(m, 18H).

[0186] Example 111. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-1-methyl-1H-indole-2-carboxamide (A111) 1H NMR (500 MHz, chloroform) δ 7.62 (s, 1H), 7.34 (s, 1H), 7.30-7.17 (m, 8H), 6.58 (s, 1H), 6.10 (s, 1H), 5.61 (s, 1H), 5.41 (s, 1H), 4.83 (s, 1H), 4.48 (s, 1H), 4.37 (s, 1H), 4.32 (s, 1H), 3.76-3.72 (m , 3H), 3.24(d, J=17.6Hz, 2H), 2.57(s, 1H), 2.08-2.04(m, 2H), 1.80(s, 1H), 1.76( s, 1H), 1.71-1.65(m, 2H), 1.56(d, J=15.2Hz, 2H), 1.21(s, 1H), 1.10-0.97(m, 6H).

[0187] Example 112. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1-methyl-1H-indole-2-carboxamide (A112) 1 H NMR (500 MHz, chloroform) δ 7.57 (s, 1H), 7.51 (s, 1H), 7.31 (s, 1H), 7.25 (s, 1H), 7.18 (d, J = 5.1 Hz, 2H), 5.92 (s, 1H), 5.59 (s, 1H), 5.43 (s, 1H), 4.99 (s, 1H), 4.47 (s, 1H), 3.74-3.70 (m, 3H), 3. 24(d, J=16.8Hz, 2H), 2.71(s, 1H), 2.41(s, 1H), 2.08-2.04(m, 2H), 1.76(dd, J=34 .2, 16.8Hz, 4H), 1.55(s, 1H), 1.45(s, 1H), 1.30-1.26(m, 9H), 1.09-0.96(m, 6H).

[0188] Example 113. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-1-methyl-1H-indole-2-carboxamide (A113) 1H NMR (500 MHz, chloroform) δ 7.57 (s, 1H), 7.51 (s, 1H), 7.31 (s, 1H), 7.25 (s, 1H), 7.18 (d, J = 5.1 Hz, 2H), 5.92 (s, 1H), 5.59 (s, 1H), 5.43 (s, 1H), 4.99 (s, 1H), 4.47 (s, 1H), 3.74-3.70 (m, 3H), 3. 24(d, J=16.8Hz, 2H), 2.71(s, 1H), 2.41(s, 1H), 2.08-2.04(m, 2H), 1.76(dd, J=34 .2, 16.8Hz, 4H), 1.55(s, 1H), 1.45(s, 1H), 1.30-1.26(m, 9H), 1.09-0.96(m, 6H).

[0189] Example 114. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A114) 1 H NMR (500MHz, chloroform)δ 9.48(s, 5H), 7.69(s, 5H), 7.37(s, 5H), 7.29(d, J=6.5Hz, 3H), 7.28-7.15(m, 23H), 7. 06(s, 5H), 6.19(s, 5H), 5.64(s, 5H), 5.49(s, 5H), 5.18(s, 5H), 4.42(s, 5H), 4.35(d, J =14.2Hz, 10H), 3.45(s, 5H), 3.35(d, J=1.5Hz, 9H), 3.05(s, 5H), 2.19(s, 4H), 2.09-2 .05(m, 10H), 1.92(s, 4H), 1.68(s, 5H), 1.58(s, 5H), 1.52(s, 5H), 1.02-0.89(m, 31H).

[0190] Example 115. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A115) 1H NMR (500MHz, chloroform) δ 8.36(s, 1H), 7.60(s, 1H), 7.40(s, 1H), 7.06(s, 1H), 6.45(s, 1H), 6.04( s, 1H), 5.52(d, J=2.2Hz, 2H), 4.99(s, 1H), 4.68(s, 1H), 3.45(s, 1H), 3. 35(s, 1H), 2.72(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.93(s, 1H), 1. 70(d, J=9.3Hz, 2H), 1.49(s, 1H), 1.32-1.28(m, 9H), 1.11-1.02(m, 6H).

[0191] Example 116. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A116) 1 H NMR (500 MHz, chloroform) δ 9.33 (s, 1H), 8.27 (s, 1H), 7.54 (s, 1H), 7.37 (s, 1H), 7.03 (s, 1H), 6.84 (s, 1H), 6.14 (s, 1H), 5.29 (s, 1H), 4.95 (s, 1H), 4.31 (s, 1H), 3.83 (s, 1H), 3.45 (s, 1H). H), 3.35(s, 1H), 2.73(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 2.05-1.90(m, 3 H), 1.72(s, 1H), 1.70-1.44(m, 9H), 1.44(d, J=5.3Hz, 1H), 0.98-0.85(m, 6H).

[0192] Example 117. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A117) 1H NMR (500 MHz, chloroform) δ 8.38 (s, 1H), 7.67 (s, 1H), 7.42 (s, 1H), 7.29-7.22 (m, 4H), 7.19 (s, 1H), 7.10 (d, J = 11.4 Hz, 2H), 6.65 (s, 1H), 5.62 (s, 1H), 5.55 (s, 1H), 4.99 (s, 1H), 4.48 (s, 1H), 4.37 (s, 1H), 4.33(s, 1H), 3.24(d, J=16.8Hz, 2H), 2.56(s, 1H), 2.45(s, 1H), 2.08-2.04(m, 2H), 1.80 (d, J=3.6Hz, 2H), 1.72(d, J=14.6Hz, 2H), 1.55(s, 1H), 1.46(s, 1H), 1.10-0.97(m, 6H).

[0193] Example 118. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A118) 1 H NMR (500MHz, chloroform)δ 8.59(s, 1H), 7.55(s, 1H), 7.41(s, 1H), 7.05(s, 1H), 6.20(s, 1H), 5.74(s, 1H), 5.41(s, 1H), 4.71(s, 1H), 4.48(s, 1H), 3.24(d, J=17.3Hz, 2H), 2.48(s, 1H), 2.06(t, J=2.1Hz, 3H), 1.86-1.74(m, 3H), 1.68(s, 1H), 1.58(s, 1H), 1.53(s, 1H), 1.32-1.28(m, 9H), 1.15-1.01(m, 6H).

[0194] Example 119. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A119) 1H NMR (500 MHz, chloroform) δ 8.63 (s, 1H), 8.33 (s, 1H), 7.58 (s, 1H), 7.40 (s, 1H), 7.07 (s, 1H), 6.32 (s, 1H), 5.80 (s, 1H), 5.52 (s, 1H), 4.79 (s, 1H), 4.59 (s, 1H), 3.96 (s, 1H), 3.24 (d, J = 17.9H z, 2H), 2.36(s, 1H), 2.15-2.08(m, 2H), 2.08-2.04(m, 2H), 2.00(s, 1H), 1.74-1. 68(m, 5H), 1.68-1.60(m, 3H), 1.60-1.50(m, 5H), 1.33(s, 1H), 1.13-1.01(m, 6H).

[0195] Example 120. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-quinoxaline-2-carboxamide (A120) 1 H NMR (500 MHz, chloroform) δ 8.79 (s, 1H), 8.05 (s, 1H), 8.01 (s, 1H), 7.64 (d, J = 1.5 Hz, 2H), 7.36-7.25 (m, 4H), 7.20 (s, 1H), 5.82 (s, 1H), 5.78 (s, 1H), 5.24 (s, 1H), 4.97 (s, 1H), 4.68 (s, 1H), 4.36 (s, 1H). H), 4.23(s, 1H), 3.68(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 2.21(s, 1H), 2.09-2.05(m, 2 H), 1.90(d, J=15.7Hz, 2H), 1.76(s, 1H), 1.65(s, 1H), 1.45(s, 1H), 1.10-0.97(m, 6H).

[0196] Example 121. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoxaline-2-carboxamide (A121) 1H NMR (500MHz, chloroform) δ 9.24(s, 1H), 8.11(d, J=7.7Hz, 2H), 7.85(s, 1H), 7.65(d, J=1.9Hz, 2H), 6. 22(s, 1H), 6.11(s, 1H), 5.66(s, 1H), 4.77(s, 1H), 4.62(s, 1H), 3.45(s, 1H) ), 3.35(s, 1H), 2.79(s, 1H), 2.17(s, 1H), 2.13-2.02(m, 2H), 1.92(s, 1H), 1.67(d, J=2.5Hz, 2H), 1.51(s, 1H), 1.34-1.30(m, 9H), 1.11-1.02(m, 6H).

[0197] Example 122. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoxaline-2-carboxamide (A122) 1 H NMR (500 MHz, chloroform) δ 9.29 (s, 1H), 8.09 (d, J = 18.4 Hz, 2H), 7.60 (d, J = 2.0 Hz, 2H), 6.27 (s, 1H), 6.23 (s, 1H), 5.90 (s, 1H), 5.24 (s, 1H), 4.80 (s, 1H), 4.70 (s, 1H), 3.45 (s, 1H), 3.35 (d, J = 1 .2Hz, 2H), 2.58(s, 1H), 2.18(s, 1H), 2.11-2.03(m, 2H), 1.93(s, 1H), 1.86-1.71(m , 3H), 1.71-1.60(m, 4H), 1.55-1.46(m, 4H), 1.44-1.39(m, 2H), 1.09-0.96(m, 6H).

[0198] Example 123. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-quinoxaline-2-carboxamide (A123) 1H NMR (500 MHz, chloroform) δ 9.35 (s, 1H), 8.12 (s, 1H), 7.95 (s, 1H), 7.64 (d, J = 15.8 Hz, 2H), 7.33-7.26 (m, 3H), 7.26-7.21 (m, 2H), 6.55 (s, 1H), 6.29 (s, 1H), 5.62 (d, J = 10.0 Hz, 2H), 4.84 (s, 1H), 4.54 (s, 1H), 4.16(d, J=16.2Hz, 2H), 3.24(d, J=17.4Hz, 2H), 2.98(s, 1H), 2.32(s, 1H), 2.10-2.04(m, 3H), 1.85(s, 1H), 1.78(s, 1H), 1.71(s, 1H), 1.59(s, 1H), 1.45(s, 1H), 1.13-1.00(m, 6H).

[0199] Example 124. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoxaline-2-carboxamide (A124) 1 H NMR (500MHz, chloroform) δ 9.23(s, 1H), 8.12(d, J=11.8Hz, 2H), 7.65(d, J=2.9Hz, 2H), 6.31(s, 1H), 6 .08(s, 1H), 5.70(s, 1H), 5.63(s, 1H), 4.89(s, 1H), 4.62(s, 1H), 3.24(d, J =17.3Hz, 2H), 2.62(s, 1H), 2.04(t, J=12.6Hz, 3H), 1.80(s, 1H), 1.76-1.6 9(m, 3H), 1.51(s, 1H), 1.40(s, 1H), 1.33-1.29(m, 9H), 1.12-0.99(m, 6H).

[0200] Example 125. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoxaline-2-carboxamide (A125) 1H NMR (500 MHz, chloroform) δ 9.32 (s, 1H), 8.97 (s, 1H), 8.11 (d, J = 3.7 Hz, 2H), 7.65 (d, J = 2.2 Hz, 2H), 5.73 (s, 1H), 5.60 (s, 1H), 5.56 (s, 1H), 4.72 (s, 1H), 4.51 (s, 1H), 3.31-3.20 (m, 3H), 2.59 ( s, 1H), 2.08-2.00(m, 5H), 1.81(s, 1H), 1.69(d, J=9.0Hz, 2H), 1.62(s, 1H), 1.60- 1.54(m, 3H), 1.53-1.42(m, 3H), 1.39(dd, J=11.3, 3.2Hz, 4H), 1.09-0.96(m, 6H).

[0201] Example 126. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-quinoline-2-carboxamide (A126) 1 H NMR (500 MHz, chloroform) δ 8.47 (s, 1H), 8.14 (s, 1H), 7.80 (s, 1H), 7.68 (s, 1H), 7.52 (s, 1H), 7.47 (s, 1H), 7.30-7.26 (m, 1H), 7.26-7.17 (m, 5H), 6.50 (s, 1H), 6.42 (s, 1H), 6.10 (s, 1H), 5.27 (s, 1H), 4.65 (d, J =5.3Hz, 2H), 4.40(s, 1H), 4.32(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 2.65(s, 1H), 2.19(s, 1H) ), 2.09-2.05(m, 2H), 1.93(s, 1H), 1.69(s, 1H), 1.59(d, J=10.7Hz, 2H), 1.13-1.00(m, 7H).

[0202] Example 127. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoline-2-carboxamide (A127) 1H NMR (500 MHz, chloroform) δ 8.36 (s, 1H), 8.14 (s, 1H), 7.77 (s, 1H), 7.69 (s, 1H), 7.46 (s, 1H), 7.40 (s, 1H), 6.36 (s, 1H), 6.13 (s, 1H), 6.02 (s, 1H), 5.67 (s, 1H), 4.93 (s, 1H), 4.61 (s, 1H), 3.45(s, 1H), 3.35(s, 1H), 2.63(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.92(s , 1H), 1.73(d, J=1.3Hz, 2H), 1.52(s, 1H), 1.33-1.29(m, 9H), 1.09-1.03(m, 6H).

[0203] Example 128. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoline-2-carboxamide (A128) 1 H NMR (500 MHz, chloroform) δ 9.46 (s, 1H), 8.44 (s, 1H), 8.17 (s, 1H), 7.80 (s, 1H), 7.71 (s, 1H), 7.47 (d, J = 10.8 Hz, 2H), 5.88 (s, 1H), 5.82 (s, 1H), 5.18 (s, 1H), 4.96 (s, 1H), 4.52 (s, 1H), 3.74 (s, 1H), 3.45(s, 1H), 3.35(s, 1H), 2.64(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.95(t, J=7. 9Hz, 3H), 1.71(s, 1H), 1.57(tt, J=16.6, 2.2Hz, 9H), 1.44(s, 1H), 1.11-0.98(m, 6H).

[0204] Example 129. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-4-methyl-1-oxopent-2-yl)-quinoline-2-carboxamide (A129) 1H NMR (500 MHz, chloroform) δ 8.45 (s, 1H), 8.18 (s, 1H), 7.81 (s, 1H), 7.72 (s, 1H), 7.47 (d, J = 14.9 Hz, 2H), 7.29-7.21 (m, 4H), 7.19 (s, 1H), 6.66 (s, 1H), 6.36 (s, 1H), 5.90 (s, 1H), 5.60 (s, 1H), 5.00 (s, 1H), 4. 50(s, 1H), 4.34(d, J=14.6Hz, 2H), 3.24(d, J=16.9Hz, 2H), 2.47(d, J=1.9Hz, 2H), 2.08-2 .04(m, 2H), 1.80(s, 1H), 1.77-1.69(m, 3H), 1.55(s, 1H), 1.46(s, 1H), 1.09-0.96(m, 6H).

[0205] Example 130. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoline-2-carboxamide (A130) 1 H NMR (500MHz, chloroform) δ 8.45(s, 1H), 8.17(s, 1H), 7.81(s, 1H), 7.71(s, 1H), 7.48(d, J=2.3Hz, 2H ), 5.90(s, 1H), 5.74(s, 1H), 5.54(s, 1H), 5.27(s, 1H), 5.13(s, 1H), 4.51 (s, 1H), 3.24(d, J=17.6Hz, 2H), 2.61(s, 1H), 2.08-2.04(m, 2H), 1.89-1. 64(m, 5H), 1.48(d, J=18.1Hz, 2H), 1.33-1.29(m, 9H), 1.09-0.96(m, 6H).

[0206] Example 131. N-((S)-3-cyclohexyl-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopent-2-yl)-quinoline-2-carboxamide (A131) 1H NMR (500 MHz, chloroform) δ 8.45 (s, 1H), 8.17 (s, 1H), 7.81 (s, 1H), 7.71 (s, 1H), 7.49 (d, J = 4.2 Hz, 2H), 6.05 (s, 1H), 5.83 (s, 1H), 5.54 (s, 1H), 5.39 (s, 1H), 5.11 (s, 1H), 4.52 (s, 1H), 3.30- 3.20(m, 3H), 2.61(s, 1H), 2.08-2.04(m, 2H), 2.02-1.90(m, 2H), 1.87-1.77(m, 3 H), 1.75-1.68(m, 5H), 1.55-1.44(m, 5H), 1.44-1.39(m, 2H), 1.09-0.96(m, 6H).

[0207] Example 132. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-chloro-3,8a-dihydro-2H-benzopyran-3-carboxamide (A132) 1 H NMR (500MHz, chloroform)δ 7.39-7.29(m, 2H), 7.29-7.20(m, 7H), 7.18(s, 1H), 6.65(s, 1H), 6.45(d, J=4.2Hz, 2H ), 6.24(s, 1H), 6.13(d, J=3.8Hz, 2H), 6.03(s, 1H), 5.47(s, 1H), 4.93(d, J=16.9Hz, 2 H), 4.66(s, 1H), 4.42(s, 1H), 4.33(s, 1H), 3.66(s, 1H), 3.45(s, 1H), 3.40-3.30(m, 3 H), 3.18(s, 1H), 2.96(d, J=11.1Hz, 2H), 2.18(s, 1H), 2.12-2.02(m, 2H), 1.93(s, 1H).

[0208] Example 133. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-chloro-3,8a-dihydro-2H-benzopyran-3-carboxamide (A133) 1 H NMR (500 MHz, chloroform) δ 7.27-7.21 (m, 2H), 7.21-7.11 (m, 3H), 7.10 (s, 1H), 6.49 (s, 1H), 6.31 (s, 1H), 6.20 (s, 1H), 6.13 (s, 1H), 5.96 (d, J = 15.6 Hz, 2H), 5.67 (s, 1H), 4.90 (s, 1H), 4.85 (s, 1H), 4.66 (s, 1H) , 4.14(s, 1H), 3.69(s, 1H), 3.42(d, J=26.2Hz, 2H), 3.33(d, J=15.0Hz, 2H), 3.23(s, 1H), 2 .83(s, 1H), 2.68(s, 1H), 2.17(s, 1H), 2.09-2.05(m, 2H), 1.91(s, 1H), 1.36-1.32(m, 10H).

[0209] Example 134. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-chloro-3,8a-dihydro-2H-benzopyran-3-carboxamide (A134) 1 H NMR (500MHz, chloroform)δ 8.76(s, 5H), 8.45(s, 5H), 7.29-7.23(m, 10H), 7.16(s, 5H), 7.14-7.05(m, 10H), 6.44(s, 5H), 6.29(s, 5H), 6. 03(s, 5H), 5.93(d, J=10.5Hz, 10H), 5.21(s, 5H), 5.05(s, 5H), 4.64(d, J=18.2Hz, 10H), 3.67(s, 4H), 3.48-3.4 6(m, 2H), 3.43(t, J=11.4Hz, 14H), 3.37(dt, J=43.5, 18.6Hz, 29H), 3.05(s, 5H), 2.86(s, 5H), 2.19(s, 5H), 2.0 9-2.05(m, 10H), 1.95-1.86(m, 15H), 1.72-1.64(m, 15H), 1.56-1.52(m, 9H), 1.50(s, 6H), 1.45-1.40(m, 10H).

[0210] Example 135. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-chloro-3,8a-dihydro-2H-benzopyran-3-carboxamide (A135) 1 H NMR (500 MHz, chloroform) δ 7.82 (s, 1H), 7.30-7.22 (m, 4H), 7.21-7.07 (m, 6H), 6.48 (s, 1H), 6.29 (s, 1H), 6.16 (s, 1H), 6.09 (s, 1H), 5.96 (d, J = 19.6 Hz, 2H), 5.31 (s, 1H), 4.94 (s, 1H), 4.66 (s, 1H), 4.61 (s, 1H), 4.41 (s, 1H) , 4.33(s, 1H), 3.72(s, 1H), 3.51-3.12(m, 5H), 3.24(d, J=16.9Hz, 2H), 3.24(d, J=16.9Hz, 2H), 2 .96(s, 1H), 2.43(s, 1H), 2.19(s, 1H), 2.08-2.03(m, 2H), 1.80(s, 1H), 1.73(s, 1H), 1.55(s, 1H).

[0211] Example 136. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-chloro-3,8a-dihydro-2H-benzopyran-3-carboxamide (A136) 1H NMR (500 MHz, chloroform) δ 7.32-7.26 (m, 2H), 7.18 (s, 1H), 7.15-7.08 (m, 2H), 6.45 (s, 1H), 6.28 (s, 1H), 6.02 (s, 1H), 5.94 (d, J = 3.0 Hz, 2H), 5.80 (s, 1H), 5.63 (s, 1H), 5.14 (s, 1H), 4.66 (s, 1H), 4.55 (s, 1H), 3.91 (s, 1H), 3.65(s, 1H), 3.49-3.10(m, 5H), 3.25(t, J=14.8Hz, 3H), 3.25(t, J=14.8Hz, 3H), 3.01(s, 1H), 2.5 3(s, 1H), 2.08-2.04(m, 2H), 1.94(s, 1H), 1.80(d, J=1.0Hz, 2H), 1.73(s, 1H), 1.34-1.30(m, 9H).

[0212] Example 137. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-chloro-3,8a-dihydro-2H-benzopyran-3-carboxamide (A137) 1 H NMR (500 MHz, chloroform) δ 7.30-7.26 (m, 1H), 7.26-7.14 (m, 4H), 6.52 (s, 1H), 6.47 (s, 1H), 6.14 (s, 1H), 6.04 (s, 1H), 5.96 (s, 1H), 5.87 (d, J = 16.5 Hz, 2H), 5.02 (d, J = 1.5 Hz, 2H), 4.66 (s, 1H), 4.48 (s, 1H), 3.68 (s, 1H), 3.51 (s, 1H), 3.40 (s, 1H), 3.31(d, J=10.7Hz, 2H), 3.24(d, J=17.3Hz, 2H), 3.01(d, J=17.6Hz, 2H), 2.12-2.04(m, 5H), 1.96 (s, 1H), 1.82(s, 1H), 1.75(s, 1H), 1.71-1.64(m, 3H), 1.56-1.52(m, 2H), 1.48(s, 1H), 1.45-1.40(m, 2H).

[0213] Example 138. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)benzene[d][1,3]m-dioxol-5-carboxamide (A138) 1 H NMR (500MHz, chloroform) δ 7.52(s, 1H), 7.43-7.23(m, 8H), 7.23-7.19(m, 3H), 7.16(s, 1H), 6.92( s, 1H), 6.04(s, 1H), 5.92-5.88(m, 2H), 5.21(s, 1H), 4.83(s, 1H), 4.75( s, 1H), 4.44(s, 1H), 4.38(s, 1H), 3.45(s, 1H), 3.36(d, J=13.2Hz, 2H), 2.95(s, 1H), 2.80(s, 1H), 2.18(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H).

[0214] Example 139. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)benzene[d][1,3]m-dioxol-5-carboxamide (A139) 1 H NMR (500MHz, chloroform)δ 7.48(s, 1H), 7.32(s, 1H), 7.29-7.23(m, 2H), 7.23-7.14(m, 3H), 6.91(s, 1H), 5.95(s, 1H), 5.92-5.88(m, 2H), 4.76(d, J=1.1Hz, 2H), 4.7 1(s, 1H), 3.46(d, J=12.3Hz, 2H), 3.35(s, 1H), 3.08(s, 1H), 2.99(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.93(s, 1H), 1.40-1.36(m, 9H).

[0215] Example 140. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)benzene[d][1,3]m-dioxol-5-carboxamide (A140) 1 H NMR (500MHz, chloroform)δ 7.30(dd, J=21.6, 15.7Hz, 4H), 7.28-7.23(m, 1H), 7.28-7.14(m, 4H), 6.89(s, 1H), 6. 05(s, 1H), 5.92-5.88(m, 2H), 5.08(s, 1H), 4.75(d, J=16.1Hz, 2H), 3.59(s, 1H), 3.45( d, J=2.5Hz, 2H), 3.35(s, 1H), 3.12(s, 1H), 2.99(s, 1H), 2.19(s, 1H), 2.10-2.04(m, 4H ), 1.93(s, 1H), 1.81-1.70(m, 3H), 1.58-1.54(m, 2H), 1.51(s, 1H), 1.47-1.42(m, 2H).

[0216] Example 141. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)benzene[d][1,3]m-dioxol-5-carboxamide (A141) 1 H NMR (500MHz, chloroform) δ 7.41(s, 1H), 7.36(s, 1H), 10.00-7.08(m, 14H), 6.54(s, 1H), 6.07(s, 1H) ), 5.92-5.88(m, 2H), 5.10(s, 1H), 4.42(s, 1H), 4.37(d, J=6.5Hz, 2H), 4 .30(s, 1H), 3.60(s, 1H), 3.25(t, J=13.9Hz, 3H), 3.03(s, 1H), 2.73(s, 1 H), 2.09-2.03(m, 2H), 1.79(d, J=5.2Hz, 2H), 1.73(s, 1H), 1.57(s, 1H).

[0217] Example 142. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)benzene[d][1,3]m-dioxol-5-carboxamide (A142) 1 H NMR (500MHz, chloroform)δ 8.38(s, 28H), 7.44(s, 29H), 7.30-7.23(m, 86H), 7.23-7.15(m, 82H), 7.15(d, J=1.8 Hz, 4H), 6.98(s, 29H), 5.92-5.85(m, 85H), 5.21(s, 28H), 5.00(s, 27H), 4.81(s, 28H) , 4.66(s, 28H), 3.26(t, J=21.5Hz, 87H), 2.91(s, 30H), 2.78(s, 26H), 2.21(s, 20H), 2.11-2.02(m, 61H), 2.00(s, 21H), 1.83(s, 25H), 1.77(s, 21H), 1.32-1.28(m, 251H).

[0218] Example 143. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)benzene[d][1,3]m-dioxol-5-carboxamide (A143) 1H NMR (500 MHz, chloroform) δ 8.29 (s, 1H), 7.48 (s, 1H), 7.38 (s, 1H), 7.28-7.23 (m, 2H), 7.23-7.11 (m, 3H), 6.94 (s, 1H), 6.09 (s, 1H), 5.92-5.88 (m, 2H), 5.06 (s, 1H), 4.91 (s, 1H), 4.73 (s, 1H), 4.38 (s, 1H), 3.36 (s , 1H), 3.31-3.20(m, 3H), 3.07(s, 1H), 2.85(s, 1H), 2.08-2.03(m, 4H), 1.88(s, 1H), 1.81(s, 1H), 1.78-1.69(m, 3H), 1.67(s, 1H), 1.58(s, 1H), 1.51(t, J=7.6Hz, 3H), 1.43-1.39(m, 2H).

[0219] Example 144. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)benzene[d][1,3]m-dioxol-5-carboxamide (A144) 1 H NMR (500 MHz, chloroform) δ 8.29 (s, 1H), 7.48 (s, 1H), 7.38 (s, 1H), 7.28-7.23 (m, 2H), 7.23-7.11 (m, 3H), 6.94 (s, 1H), 6.09 (s, 1H), 5.92-5.88 (m, 2H), 5.06 (s, 1H), 4.91 (s, 1H), 4.73 (s, 1H), 4.38 (s, 1H), 3.36 (s , 1H), 3.31-3.20(m, 3H), 3.07(s, 1H), 2.85(s, 1H), 2.08-2.03(m, 4H), 1.88(s, 1H), 1.81(s, 1H), 1.78-1.69(m, 3H), 1.67(s, 1H), 1.58(s, 1H), 1.51(t, J=7.6Hz, 3H), 1.43-1.39(m, 2H).

[0220] Example 145. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoronicotinamide (A145) 1 H NMR (500MHz, chloroform) δ 8.60(d, J=2.3Hz, 2H), 7.83(s, 1H), 7.23(d, J=6.4Hz, 1H), 7.22-7.08(m , 5H), 5.97(s, 1H), 5.48(s, 1H), 4.88(s, 1H), 4.38(s, 1H), 4.01(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.26(s, 1H), 2.96(s, 1H), 2.69(s, 1H), 2.40( s, 1H), 2.16(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H), 1.32-1.28(m, 10H).

[0221] Example 146. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoronicotinamide (A146) 1 H NMR (500 MHz, chloroform) δ 8.82 (s, 1H), 8.50 (s, 1H), 7.89 (s, 1H), 7.31-7.24 (m, 4H), 7.17 (s, 1H), 6.22 (s, 1H), 5.95 (s, 1H), 5.47 (s, 1H), 5.14 (s, 1H), 4.38 (s, 1H), 3.45 (s, 1H), 3.37 (d, J = 16.6 Hz, 2 H), 3.29(s, 1H), 2.86(s, 1H), 2.47(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.93(s, 1H) ), 1.91-1.79(m, 2H), 1.70(s, 1H), 1.58-1.51(m, 4H), 1.50(s, 1H), 1.45-1.40(m, 2H).

[0222] Example 147. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoronicotinamide (A147) 1 H NMR (500 MHz, chloroform) δ 8.80 (s, 1H), 8.58 (s, 1H), 7.99 (s, 1H), 7.41-7.32 (m, 2H), 7.32-7.18 (m, 6H), 7.16 (s, 1H), 7.09 (s, 1H), 6.51 (s, 1H), 6.23 (s, 1H), 5.85 (s, 1H), 4.87 (s, 1H), 4.36 (s , 1H), 4.30(d, J=5.9Hz, 2H), 3.24(d, J=15.2Hz, 2H), 3.09(s, 1H), 2.82(s, 1H), 2. 57(s, 1H), 2.08-2.04(m, 2H), 1.98(s, 1H), 1.82(s, 1H), 1.76(s, 1H), 1.65(s, 1H).

[0223] Example 148. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoronicotinamide (A148) 1 H NMR (500MHz, chloroform) δ 8.82(s, 1H), 8.52(s, 1H), 8.05(s, 1H), 7.30-7.22(m, 4H), 7.15(s, 1H) , 6.03(s, 1H), 5.79(s, 1H), 5.01(s, 1H), 4.84(s, 1H), 4.27(s, 1H), 3.3 6(s, 1H), 3.24(d, J=14.9Hz, 2H), 2.95(s, 1H), 2.72(s, 1H), 2.07(t, J= 5.5Hz, 3H), 1.85(s, 1H), 1.78(s, 1H), 1.70(s, 1H), 1.32-1.28(m, 9H).

[0224] Example 149. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoronicotinamide (A149) 1 H NMR (500MHz, chloroform)δ 8.86(s, 7H), 8.52(s, 7H), 7.93(s, 7H), 7.42(s, 7H), 7.24-7.19(m, 14H), 7.14(s, 7H), 7.1 2-7.04(m, 14H), 6.15(d, J=16.5Hz, 14H), 5.79(s, 7H), 4.89(s, 7H), 4.62(s, 7H), 3.87(s, 7H), 3.27(t, J=22.0Hz, 22H), 3.17(t, J=12.5Hz, 1H), 3.11(d, J=17.0Hz, 14H), 2.12(s, 5H) ), 2.10-2.01(m, 16H), 2.01-1.94(m, 14H), 1.87(s, 5H), 1.80(s, 5H), 1.67-1.58(m, 67H).

[0225] Example 150. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (A150) 1 H NMR (500MHz, chloroform) δ 7.52(s, 5H), 7.32-7.14(m, 55H), 7.13(t, J=1.5Hz, 1H), 7.07(s, 5H), 6.0 9(s, 5H), 6.01(s, 5H), 5.64(s, 5H), 5.02(s, 5H), 4.84(s, 5H), 4.36(s, 5H) , 4.29(s, 5H), 3.89-3.85(m, 15H), 3.45(s, 5H), 3.35(s, 4H), 3.17(s, 4H) , 3.11(s, 5H), 2.93(s, 5H), 2.19(s, 4H), 2.10-2.04(m, 10H), 1.92(s, 4H).

[0226] Example 151. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (A151) 1 H NMR (500MHz, chloroform) δ 7.86(s, 1H), 7.42(s, 1H), 10.00-7.19(m, 6H), 7.17(s, 1H), 7.05(s, 1H) ), 5.92(d, J=15.2Hz, 2H), 5.77(s, 1H), 5.06(s, 1H), 4.87(s, 1H), 3.89 -3.85(m, 3H), 3.45(s, 1H), 3.35(s, 1H), 3.18(s, 1H), 2.88(d, J=18.2H) z, 2H), 2.17(s, 1H), 2.13-2.02(m, 2H), 1.92(s, 1H), 1.34-1.30(m, 9H).

[0227] Example 152. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (A152) 1 H NMR (500 MHz, chloroform) δ 7.28-7.17 (m, 5H), 7.15 (s, 1H), 7.08 (s, 1H), 6.04 (s, 1H), 5.89 (s, 1H), 4.77 (s, 1H), 4.30 (s, 1H), 4.02-3.98 (m, 3H), 3.83 (s, 1H), 3.71 (s, 1H), 3.45 (s, 1H), 3.87 (s, 1H), 3.76 (s, 1H), 3.49 (s, 1H), 3.7 ...7 (s, 1H), 3.77 (s, 1H), 3.77 (s, 1H), 3.47 (s, 1H), 3.77 (s, 1H), 3.77 (s, 1H), 3.47 (s, 1H), 3.77 (s, 1H), 3.77 (s, 1H), 3.47 (s, 1H), 3.77 (s, 1H), 3.77 H), 3.35(s, 1H), 3.30(s, 1H), 3.05(s, 1H), 2.97(s, 1H), 2.65(s, 1H), 2.20(s , 1H), 2.09-2.05(m, 2H), 2.04-2.00(m, 1H), 1.91(s, 1H), 1.67-1.55(m, 7H).

[0228] Example 153. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (A153) 1 H NMR (500MHz, chloroform)δ 8.58(s, 7H), 8.29(s, 7H), 7.42(s, 7H), 7.32-7.24(m, 28H), 7.18(dt, J=57.0, 25.2Hz, 40H ), 7.08-7.07(m, 2H), 6.51(s, 7H), 6.01(s, 7H), 5.10(s, 7H), 4.81(s, 7H), 4.38(s, 7H), 4. 32(s, 7H), 3.93-3.89(m, 21H), 3.30(d, J=53.3Hz, 17H), 3.21(s, 3H), 3.21(s, 6H), 2.99(s , 7H), 2.17(s, 6H), 2.11-2.01(m, 14H), 1.76(d, J=12.9Hz, 12H), 1.68(s, 5H), 1.42(s, 6H).

[0229] Example 154. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (A154) 1 H NMR (500 MHz, chloroform) δ 9.02 (s, 1H), 7.53 (s, 1H), 7.31-7.25 (m, 2H), 7.17 (dd, J = 16.8, 9.4 Hz, 4H), 6.20 (s, 1H), 6.11 (s, 1H), 5.60 (s, 1H), 5.16 (s, 1H), 4.76 (s, 1H), 3.90-3.8 6(m, 3H), 3.24(d, J=15.4Hz, 2H), 3.12(s, 1H), 2.92(d, J=17.7Hz, 2H), 2.05 (t, J=4.4Hz, 3H), 1.82(s, 1H), 1.76(s, 1H), 1.56(s, 1H), 1.31-1.27(m, 9H).

[0230] Example 155. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (A155) 1 H NMR (500 MHz, chloroform) δ 8.38 (s, 1H), 7.28-7.22 (m, 2H), 7.22-7.11 (m, 3H), 7.04 (s, 1H), 6.62 (s, 1H), 5.99 (s, 1H), 4.76 (s, 1H), 4.62 (s, 1H), 4.30 (s, 1H), 3.83-3.79 (m, 3H), 3.26 (dd, J = 17.5, 12.1 Hz, 4H) , 3.05(s, 1H), 3.01(s, 1H), 2.72(s, 1H), 2.20-2.13(m, 3H), 2.09-2.03(m, 2H), 1.86(s, 1H) ), 1.80(s, 1H), 1.72-1.66(m, 3H), 1.56(t, J=5.2Hz, 3H), 1.49(s, 1H), 1.46-1.41(m, 2H).

[0231] Example 156. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-bromoimidazo[1,2-a]pyridine-2-carboxamide (A156) 1 H NMR (500 MHz, chloroform) δ 8.45 (s, 1H), 7.77 (s, 1H), 7.68 (s, 1H), 7.58 (s, 1H), 7.40 (s, 1H), 7.32-7.26 (m, 4H), 7.26-7.11 (m, 7H), 6.00 (s, 1H), 5.04 (s, 1H), 4.92 (s, 1H), 4.7 7(s, 1H), 4.38(s, 1H), 4.30(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.27(s, 1H) ), 3.11(s, 1H), 2.85(s, 1H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H).

[0232] Example 157. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-bromoimidazo[1,2-a]pyridine-2-carboxamide (A157) 1 H NMR (500MHz, chloroform) δ 8.80(s, 1H), 8.37(s, 1H), 7.69(d, J=2.2Hz, 2H), 7.59(s, 1H), 7.28-7.21 (m, 2H), 7.21-7.11(m, 3H), 6.78(s, 1H), 5.98(s, 1H), 5.45(s, 1H), 4.93(s , 1H), 4.66(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.22(s, 1H), 2.96(d, J=29. 5Hz, 2H), 2.19(s, 1H), 2.09-2.05(m, 2H), 1.92(s, 1H), 1.34-1.30(m, 9H).

[0233] Example 158. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-bromoimidazo[1,2-a]pyridine-2-carboxamide (A158) 1 H NMR (500 MHz, chloroform) δ 8.39 (s, 1H), 7.69 (d, J = 16.1 Hz, 2H), 7.60 (s, 1H), 7.36-7.20 (m, 9H), 7.19 (d, J = 13.6 Hz, 2H), 6.50 (s, 1H), 6.28 (s, 1H), 6.16 (s, 1H), 6.10 (s, 1H), 4.75 (d, J = 4 .7Hz, 2H), 4.39(s, 1H), 4.30(s, 1H), 3.24(t, J=8.9Hz, 3H), 3.01(s, 1H), 2.72( s, 1H), 2.11-2.01(m, 2H), 1.84(s, 1H), 1.80(s, 1H), 1.73(s, 1H), 1.36(s, 1H).

[0234] Example 159. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-bromoimidazo[1,2-a]pyridine-2-carboxamide (A159) 1 H NMR (500MHz, chloroform) δ 8.41(s, 1H), 8.18(s, 1H), 7.79-7.57(m, 3H), 7.27-7.21(m, 2H), 7.21-7 .10(m, 3H), 6.09(s, 1H), 5.52(s, 1H), 5.08(s, 1H), 4.74(s, 1H), 4.45(s, 1H), 3.25(t, J=9.9Hz, 3H), 3.01(s, 1H), 2.85(s, 1H), 2.10-2.02(m, 2H) , 1.88(s, 1H), 1.81(s, 1H), 1.68(s, 1H), 1.60(s, 1H), 1.35-1.31(m, 9H).

[0235] Example 160. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-bromoimidazo[1,2-a]pyridine-2-carboxamide (A160) 1 H NMR (500 MHz, chloroform) δ 9.87 (s, 1H), 8.26 (s, 1H), 7.68 (s, 1H), 7.57 (d, J = 11.2 Hz, 2H), 7.27-7.21 (m, 2H), 7.21-7.10 (m, 3H), 6.07 (s, 1H), 4.94 (s, 1H), 4.78 (s, 1H), 4.51 (s, 1H), 3.54 (s, 1H), 3.45 (s, 1H), 3.24 (d , J=16.2Hz, 2H), 3.17(s, 1H), 2.97(s, 1H), 2.92(s, 1H), 2.28(s, 1H), 2.09-2.04(m, 4H), 1.81( s, 1H), 1.74(s, 1H), 1.70(s, 1H), 1.59-1.52(m, 4H), 1.49(d, J=1.6Hz, 2H), 1.47-1.41(m, 2H).

[0236] Example 161. N-((S)-1-(((S)-4-(phenylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-benzo[d]imidazole-2-carboxamide (A161) 1 H NMR (500MHz, chloroform)δ 7.62(d, J=18.9Hz, 2H), 7.34-7.23(m, 9H), 7.23-7.12(m, 3H), 6.92(s, 1H), 6.17(s, 1H), 5.35(s, 1H), 5.03(s, 1H), 4.70(d, J=4.7Hz, 2H), 4.38(s, 1H), 4.33(s, 1H), 4.03(s, 1H), 3.35(s, 1H), 3.27(s, 1H), 3.04(s, 1H), 2.82(s, 1H), 2.17(s, 1H), 2.12-2.03(m, 2H), 1.93(s, 1H).

[0237] Example 162. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-benzo[d]imidazole-2-carboxamide (A162) 1 H NMR (500MHz, chloroform) δ 7.68(s, 1H), 7.59(s, 1H), 7.30-7.25(m, 2H), 7.22-7.16(m, 2H), 7.16 -7.06(m, 3H), 6.17(s, 1H), 5.89(s, 1H), 5.84(s, 1H), 5.11(s, 1H), 4.9 8(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.25(s, 1H), 3.04(s, 1H), 2.28(s , 1H), 2.19(s, 1H), 2.11-2.03(m, 2H), 1.92(s, 1H), 1.35-1.31(m, 9H).

[0238] Example 163. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-benzo[d]imidazole-2-carboxamide (A163) 1 H NMR (500MHz, chloroform) δ 7.70(s, 1H), 7.57(d, J=4.5Hz, 2H), 7.22(dd, J=17.6, 7.1Hz, 4H), 7.18-7.07(m, 3H), 5.97(s, 1H), 5.74(s, 1H), 5.03(s, 1H), 4.50(d, J=11.0Hz, 2H), 4.41(s, 1H), 3.61(s, 1H), 3.45(s, 1H), 3.35(s, 1H), 3.21(s, 1H), 3.03(s, 1H), 2.80(s, 1H), 2.17(s, 1H), 2.09-2.05(m, 2H), 1.93-1. 78(m, 3H), 1.71(s, 1H), 1.64-1.60(m, 2H), 1.58-1.54(m, 2H), 1.50(s, 1H), 1.48-1.42(m, 2H).

[0239] Example 164. N-((S)-1-(((S)-4-(phenylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-benzo[d]imidazole-2-carboxamide (A164) 1 H NMR (500 MHz, chloroform) δ 7.73 (s, 1H), 7.67 (s, 1H), 7.38 (t, J = 17.9 Hz, 3H), 7.27-7.13 (m, 9H), 7.11 (s, 1H), 6.99 (s, 1H), 6.45 (s, 1H), 5.48 (s, 1H), 4.94 (d, J = 7.2 Hz, 2H), 4.89 (s, 1H), 4.06 (s, 1H), 4.04 (s, 1H), 4.03 (s, 1H), 4.02 (s, 1H), 4.01 ... .32(s, 1H), 4.26(s, 1H), 3.42(s, 1H), 3.24(d, J=18.2Hz, 2H), 3.06(s, 1H), 2.92 (s, 1H), 2.13(s, 1H), 2.11-2.00(m, 2H), 1.92(s, 1H), 1.86(s, 1H), 1.79(s, 1H).

[0240] Example 165. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-benzo[d]imidazole-2-carboxamide (A165) 1 H NMR (500MHz, chloroform)δ 9.34(s, 4H), 7.98(s, 4H), 7.79(s, 4H), 7.62(s, 4H), 7.54(s, 4H), 7.42-7.28 (m, 23H), 7.28-7.26(m, 2H), 7.16(s, 4H), 5.87(s, 4H), 5.43(s, 4H), 5.16(s, 4) H), 4.27(s, 4H), 3.33-3.20(m, 12H), 2.94(s, 4H), 2.82(s, 4H), 2.08-2.04(m, 8H), 1.96(s, 3H), 1.82(s, 3H), 1.76(s, 3H), 1.63(s, 3H), 1.33-1.29(m, 36H).

[0241] Example 166. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-benzo[d]imidazole-2-carboxamide (A166) 1H NMR (500 MHz, chloroform) δ 8.45 (s, 1H), 8.24 (s, 1H), 7.65 (s, 1H), 7.60 (s, 1H), 7.53 (s, 1H), 7.24 (dd, J = 20.9, 2.1 Hz, 4H), 7.16-7.04 (m, 3H), 5.61 (s, 1H), 5.36 (s, 1H), 5.09 (s, 1H), 4.63 (s, 1H), 3.50 (s, 1H), 3.41 (s, 1H) , 3.24(d, J=15.7Hz, 2H), 2.98(s, 1H), 2.66(s, 1H), 2.57(s, 1H), 2.27-2.16(m, 2H), 2.08-2.04(m , 2H), 1.98(s, 1H), 1.85(s, 1H), 1.78(s, 1H), 1.72(s, 1H), 1.63-1.55(m, 4H), 1.55-1.44(m, 3H).

[0242] Example 167. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-5-carboxamide (A167) 1 H NMR (500MHz, chloroform)δ 9.78(s, 1H), 8.99(s, 1H), 8.23(s, 1H), 7.81(s, 1H), 7.49(d, J=90.0Hz, 2H), 7.40-7.3 8(m, 4H), 7.30(d, J=15.0Hz, 5H), 7.19(s, 34H), 7.14(s, 4H), 7.07(s, 1H), 6.56(s, 1H) , 6.10(s, 1H), 5.29(s, 1H), 5.09(s, 1H), 4.85(s, 1H), 4.34(s, 2H), 3.63(s, 21H), 3.51 (s, 1H), 3.33(s, 1H), 3.08(s, 1H), 2.65(s, 1H), 2.20(s, 1H), 2.02(s, 1H), 1.90(s, 1H).

[0243] Example 168. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-5-carboxamide (A168) 1 H NMR (500 MHz, chloroform) δ 8.95 (s, 1H), 8.26 (d, J = 60.3 Hz, 2H), 7.78 (s, 1H), 7.55 (s, 1H), 7.31-7.18 (m, 4H), 7.16 (s, 1H), 7.31-6.84 (m, 7H), 6.55 (d, J = 16.4 Hz, 2H), 5.97 (s, 1 H), 5.15(s, 1H), 4.79(s, 1H), 3.63(s, 1H), 3.51(s, 1H), 3.32(s, 1H), 3.07 (s, 1H), 2.54(s, 1H), 2.21(s, 1H), 2.02(s, 1H), 1.91(s, 1H), 1.26(s, 9H).

[0244] Example 169. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-5-carboxamide (A169) 1 H NMR (500MHz, chloroform)δ 8.98(s, 13H), 8.34(s, 13H), 8.22(s, 14H), 7.80(s, 13H), 7.57(s, 14H), 7.37-7.20(m, 2H), 7.18(s, 14) H), 7.37-6.87(m, 82H), 6.56(s, 13H), 6.49(s, 13H), 5.99(s, 13H), 5.17(s, 7H), 4.95(s, 5H), 4.79(s, 7) H), 3.64(s, 6H), 3.52(s, 6H), 3.33(s, 15H), 3.08(s, 14H), 2.55(s, 5H), 2.20(d, J=14.4Hz, 31H), 2.02( s, 14H), 1.88(d, J=38.0Hz, 37H), 1.80(s, 5H), 1.62(s, 9H), 1.37(s, 27H), 1.31(s, 11H), 1.20(s, 23H).

[0245] Example 170. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-5-carboxamide (A170) 1 H NMR (500MHz, chloroform)δ 8.99(s, 2H), 8.23(s, 2H), 8.06(s, 2H), 7.81(s, 2H), 7.58(s, 2H), 7.29(d, J=15.0Hz, 9H), 7.19(s, 1H), 7.14(s, 9H), 7.05(d, J=24.0Hz, 3H), 6.56(s, 2H), 6.06(s, 2H), 5.05(s, 2H), 4.76(s, 1H), 4.34(s, 4H), 3.55-2.80(m, 10H), 3.48-2.77(m, 10H), 3.28-2.80(m, 8H), 2.8 7-2.77(m, 1H), 2.70(s, 1H), 2.34(s, 1H), 2.01(s, 1H), 1.91(d, J=2.6Hz, 2H), 1.60(s, 1H).

[0246] Example 171. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-5-carboxamide (A171) 1 H NMR (500 MHz, chloroform) δ 8.99 (s, 1H), 8.23 ​​(s, 1H), 7.91 (s, 1H), 7.81 (s, 1H), 7.58 (s, 1H), 7.26-7.21 (m, 4H), 7.19 (s, 1H), 7.26-6.88 (m, 6H), 6.57 (d, J = 15.1 Hz, 2H), 6.06 (s, 1H), 5.06 (s, 1H). , 4.71(s, 1H), 3.33(s, 1H), 3.21(d, J=15.0Hz, 2H), 3.08(s, 1H), 2.93(s, 1H), 2.43( s, 1H), 2.39(s, 1H), 2.01(s, 1H), 1.91(d, J=1.1Hz, 1H), 1.58(s, 13H), 1.27(s, 9H).

[0247] Example 172. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-1H-indole-5-carboxamide (A172) 1 H NMR (500 MHz, chloroform) δ 8.99 (s, 1H), 8.23 ​​(s, 1H), 7.81 (s, 1H), 7.68 (s, 1H), 7.58 (s, 1H), 7.26-7.21 (m, 7H), 7.19 (s, 1H), 7.26-6.88 (m, 6H), 6.53 (d, J = 28.7 Hz, 2H), 6.50-6.48 (m, 5H), 6.08 (s, 1H), 5.06 (s, 1H), 4.95 (s, 1H), 4.70 (s, 1H) ), 3.33(s, 1H), 3.21(d, J=15.0Hz, 2H), 3.08(s, 1H), 2.94(s, 1H), 2.44(d, J=13.0Hz, 2H), 2.19(s, 2H), 2. 03-1.73(m, 5H), 1.84(s, 3H), 1.84(s, 2H), 1.60(d, J=15.4Hz, 2H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0248] Example 173. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoro-1H-indole-2-carboxamide (A173) 1H NMR (500MHz, chloroform) δ 8.75(s, 2H), 8.14(s, 2H), 7.54(d, J=24.9Hz, 4H), 7.37-7.24(m, 13H), 7.17(s, 1H), 7.11(d, J=10.0Hz, 11H), 6.85(s, 2H), 6.14(s, 2H), 5.18 (s, 2H), 4.86(s, 1H), 4.33(s, 4H), 3.65(s, 1H), 3.53(s, 1H), 3.28(s, 4H), 3.03(s, 1H), 2.54(s, 2H), 2.22(s, 2H), 2.02(s, 2H), 1.93(s, 1H).

[0249] Example 174. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoro-1H-indole-2-carboxamide (A174) 1 H NMR (500MHz, chloroform)δ 8.73(s, 1H), 8.12(s, 1H), 7.55(d, J=25.0Hz, 2H), 7.51(s, 3H), 7.16(dd, J=31.6, 6.6Hz, 7H), 6.56(s, 1H), 6.10(s, 1H), 5.19(s, 1H) , 4.83(s, 1H), 3.65(s, 1H), 3.54(s, 1H), 3.29(s, 1H), 3.04(s, 1H), 2.58(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.92(s, 5H), 1.27(s, 9H).

[0250] Example 175. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoro-1H-indole-2-carboxamide (A175) 1H NMR (500 MHz, chloroform) δ 8.74 (s, 1H), 8.08 (s, 1H), 7.55 (d, J = 25.0 Hz, 2H), 7.51 (s, 3H), 7.19 (d, J = 2.2 Hz, 2H), 7.13 (d, J = 10.0 Hz, 5H), 6.44 (s, 1H), 6.11 (s, 1H), 5.19 (s, 1H), 4.83 (s, 1H), 3.67 (d, J=15.7Hz, 1H), 3.54(s, 1H), 3.29(s, 1H), 3.04(s, 1H), 2.58(s, 1H), 2.22(s, 1H), 2.0 2(s, 1H), 1.92(s, 1H), 1.74(s, 1H), 1.46(t, J=12.5Hz, 3H), 1.21(s, 1H), 1.11(s, 1H).

[0251] Example 176. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoro-1H-indole-2-carboxamide (A176) 1 H NMR (500MHz, chloroform)δ 8.71(s, 2H), 8.61(s, 2H), 7.69(s, 2H), 7.58(s, 2H), 7.53(s, 1H), 7.33-7.20(m , 12H), 7.19(s, 1H), 7.13(d, J=10.0Hz, 10H), 5.84(s, 2H), 5.09(s, 1H), 4.57(s , 1H), 4.34(s, 4H), 3.29(s, 1H), 3.21(d, J=15.0Hz, 4H), 3.04(s, 2H), 2.73(s, 1 H), 2.41(s, 1H), 2.28(s, 1H), 2.01(s, 1H), 1.91(d, J=4.5Hz, 2H), 1.53(s, 1H).

[0252] Example 177. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoro-1H-indole-2-carboxamide (A177) 1H NMR (500 MHz, chloroform) δ 8.68 (s, 1H), 8.29 (s, 1H), 7.54 (d, J = 25.0 Hz, 2H), 7.49 (s, 3H), 7.24 (s, 1H), 7.17 (s, 1H), 7.11 (d, J = 10.0 Hz, 5H), 6.61 (s, 1H), 5.90 (s, 1H), 5.05 (s, 1H), 4.68 (s , 1H), 3.28(s, 1H), 3.22(s, 1H), 3.11(d, J=77.9Hz, 2H), 2.85(s, 1H), 2.33(s, 1H) ), 2.13(s, 1H), 2.01(s, 1H), 1.89(d, J=13.2Hz, 11H), 1.53(s, 5H), 1.27(s, 9H).

[0253] Example 178. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-fluoro-1H-indole-2-carboxamide (A178) 1 H NMR (500 MHz, chloroform) δ 8.69 (s, 1H), 8.21 (s, 1H), 7.58 (s, 1H), 7.53 (s, 1H), 7.23 (s, 1H), 7.19 (s, 1H), 7.13 (d, J = 10.0 Hz, 5H), 6.53 (s, 1H), 5.93 (s, 1H), 5.07 (s, 1H), 4.95 (s, 1H), 4.67 (s, 1H), 3.29 (s, 1H), 3 .25-2.88(m, 3H), 2.85(s, 1H), 2.36(s, 1H), 2.17(d, J=18.2Hz, 3H), 2.01(s, 1H), 1.90(d, J= 11.3Hz, 1H), 1.84(s, 2H), 1.62(s, 1H), 1.53(s, 1H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0254] Example 179. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-fluoro-1H-indole-2-carboxamide (A179) 1 H NMR (500 MHz, chloroform) δ 8.73 (s, 1H), 8.13 (s, 1H), 7.95 (s, 1H), 7.32-7.18 (m, 7H), 7.08 (d, J = 49.9 Hz, 6H), 7.03 (s, 1H), 7.03 (s, 1H), 6.74 (s, 1H), 6.16 (s, 1H), 5.20 (s, 1H), 4. 86(s, 1H), 4.33(s, 2H), 3.66(s, 1H), 3.54(s, 1H), 3.16(d, J=124.8Hz, 2H), 3.01(d, J=6.4Hz, 1H), 2.57(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.93(s, 1H).

[0255] Example 180. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-fluoro-1H-indole-2-carboxamide (A180) 1 H NMR (500 MHz, chloroform) δ 8.71 (s, 1H), 8.11 (s, 1H), 7.96 (s, 1H), 7.46-6.88 (m, 8H), 7.04 (s, 1H), 7.04 (s, 1H), 6.57 (s, 1H), 6.10 (s, 1H), 5.19 (s, 1H), 4.83 (s, 1H), 3.65 (s, 1H), 3.54 (s, 1H), 3.29 (s, 1H), 3.04 (s, 1H), 2.58 (s, 1H), 2.22 (s, 1H), 2.02 (s, 1H), 1.92 (s, 1H), 1.27 (s, 9H).

[0256] Example 181. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-fluoro-1H-indole-2-carboxamide (A181) 1H NMR (500MHz, chloroform)δ 8.71(s, 2H), 8.04(s, 2H), 7.96(s, 2H), 7.46-6.88(m, 16H), 7.04(s, 2H), 7.04( s, 2H), 6.46(s, 2H), 6.12(s, 2H), 5.20(s, 2H), 4.83(s, 1H), 3.67(d, J=17.5Hz, 3 H), 3.54(s, 1H), 3.29(s, 3H), 3.04(s, 1H), 2.58(s, 1H), 2.22(s, 1H), 2.02(s, 2) H), 1.93(s, 1H), 1.74(s, 2H), 1.46(t, J=12.5Hz, 6H), 1.21(s, 3H), 1.11(s, 2H).

[0257] Example 182. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-fluoro-1H-indole-2-carboxamide (A182) 1 H NMR (500MHz, chloroform)δ 8.68(s, 2H), 8.30(s, 2H), 7.96(s, 2H), 7.40(s, 2H), 7.28(t, J=11.5Hz, 12H), 7.1 5(dd, J=57.0, 32.0Hz, 15H), 7.04(s, 2H), 7.04(s, 2H), 5.92(s, 2H), 5.05(s, 1H), 4 .71(s, 1H), 4.34(s, 4H), 3.29(s, 1H), 3.21(d, J=15.0Hz, 4H), 3.04(s, 2H), 2.86( s, 1H), 2.39(s, 1H), 2.18(s, 1H), 2.01(s, 1H), 1.90(d, J=6.3Hz, 4H), 1.54(s, 1H).

[0258] Example 183. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-fluoro-1H-indole-2-carboxamide (A183) 1H NMR (500MHz, chloroform) δ 8.68(s, 1H), 8.30(s, 11H), 7.96(s, 1H), 7.45-6.97(m, 8H), 7.04(s, 1H), 7.04(s, 1H), 6.62(s, 1H), 5.92(s, 1H), 5.06(s, 1H), 4.69(s, 1H), 3.29(s , 1H), 3.21(d, J=15.0Hz, 2H), 3.04(s, 1H), 2.85(s, 1H), 2.33(s, 1H), 2.1 3(s, 1H), 2.01(s, 1H), 1.90(d, J=13.5Hz, 1H), 1.53(s, 1H), 1.27(s, 9H).

[0259] Example 184. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-6-fluoro-1H-indole-2-carboxamide (A184) 1 H NMR (500 MHz, chloroform) δ 8.67 (s, 1H), 8.20 (s, 1H), 7.96 (s, 1H), 7.45-6.89 (m, 8H), 7.14 (s, 4H), 7.09 (d, J = 50.0 Hz, 5H), 7.04 (s, 1H), 6.53 (s, 1H), 5.93 (s, 1H), 5.07 (s, 1H), 4.95 (s, 1H), 4.67 (s, 1H), 3.29 (s, 1H) , 3.25-2.88(m, 3H), 2.85(s, 1H), 2.35(s, 1H), 2.17(d, J=17.6Hz, 3H), 2.01(s, 1H), 1.90(d, J =11.7Hz, 1H), 1.84(s, 1H), 1.62(s, 1H), 1.53(s, 1H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0260] Example 185. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A185) 1 H NMR (500MHz, chloroform)δ 8.92(s, 2H), 8.83(s, 2H), 7.84(s, 2H), 7.49(s, 2H), 7.33-7.26(m, 11H), 7.2 2(s, 2H), 7.02(d, J=21.6Hz, 6H), 6.97(dd, J=5.6, 2.6Hz, 1H), 6.77(s, 2H), 6. 28(s, 2H), 5.16(s, 2H), 4.91(s, 1H), 4.34(s, 4H), 3.67(s, 1H), 3.55(s, 1H), 3 .29(s, 3H), 3.04(s, 1H), 2.61(s, 1H), 2.23(s, 2H), 2.02(s, 2H), 1.93(s, 1H).

[0261] Example 186. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A186) 1 H NMR (500 MHz, chloroform) δ 8.75 (s, 1H), 7.97 (s, 1H), 7.45 (s, 1H), 7.31-7.15 (m, 3H), 6.97 (d, J = 7.1 Hz, 5H), 6.50 (s, 1H), 6.15 (s, 1H), 5.18 (s, 1H), 4.82 (s, 1H), 3.65 (s, 1H), 3.53 (s, 1H), 3.27 (s, 1H), 3.03 (s, 3H), 2.60 (s, 1H), 2.22 (s, 1H), 2.01 (s, 1H), 1.92 (s, 1H), 1.26 (s, 9H).

[0262] Example 187. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A187) 1H NMR (500MHz, chloroform)δ 8.79(s, 2H), 8.00(s, 2H), 7.48(s, 2H), 7.31(d, J=14.5Hz, 4H), 7.19(s, 2H), 7.01( d, J=5.2Hz, 5H), 6.40(s, 2H), 6.18(s, 2H), 5.20(s, 2H), 4.85(s, 1H), 3.68(d, J=15 .6Hz, 3H), 3.55(s, 1H), 3.29(s, 1H), 3.04(s, 3H), 2.61(s, 2H), 2.23(s, 1H), 2.02( s, 2H), 1.93(s, 1H), 1.74(s, 2H), 1.46(t, J=12.5Hz, 6H), 1.21(s, 3H), 1.11(s, 2H).

[0263] Example 188. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A188) 1 H NMR (500MHz, chloroform)δ 9.00(s, 4H), 8.91(s, 4H), 7.70(s, 4H), 7.49(d, J=3.7Hz, 8H), 7.29(dd, J=9.6, 5.4H z, 26H), 7.21(s, 5H), 7.00(d, J=5.1Hz, 11H), 6.69(s, 4H), 4.96(d, J=17.8Hz, 6H), 4 .33(s, 8H), 3.29(s, 3H), 3.21(d, J=15.0Hz, 8H), 2.96(d, J=80.6Hz, 8H), 2.85-2.81 (m, 1H), 2.48(s, 4H), 2.27(s, 4H), 2.00(d, J=2.8Hz, 4H), 1.91(s, 6H), 1.53(s, 2H).

[0264] Example 189. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A189) 1 H NMR (500 MHz, chloroform) δ 8.57 (s, 1H), 7.45 (s, 1H), 7.32 (d, J = 18.3 Hz, 2H), 7.20 (d, J = 6.7 Hz, 2H), 7.04 (s, 1H), 7.00 (s, 1H), 6.57 (s, 1H), 5.75 (s, 1H), 5.11 (s, 1H), 4.79 (s, 1H), 3 .29(s, 1H), 3.21(d, J=15.0Hz, 2H), 3.04(s, 1H), 2.75(s, 1H), 2.47(s, 1H), 2 .36(s, 1H), 2.01(s, 1H), 1.95(s, 1H), 1.91(s, 1H), 1.51(s, 1H), 1.27(s, 9H).

[0265] Example 190. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-4,6-dichloro-1H-indole-2-carboxamide (A190) 1 H NMR (500 MHz, chloroform) δ 8.77 (s, 1H), 7.93 (s, 1H), 7.48 (s, 41H), 7.34-7.15 (m, 3H), 7.00 (s, 1H), 6.83 (s, 2H), 6.56 (s, 1H), 6.15 (s, 1H), 5.71 (s, 1H), 5.05 (s, 2H), 4.95 (s, 2H), 4.90 (s, 1H), 3.36-3.12 (m, 4H), 3.20(s, 1H), 3.12(d, J=78.0Hz, 2H), 2.32(s, 2H), 2.31-2.17(m, 3H), 2.03-1.8 6(m, 3H), 1.84(s, 2H), 1.62(s, 1H), 1.49(s, 2H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0266] Example 191. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-methoxy-1H-indole-2-carboxamide (A191) 1 H NMR (500 MHz, chloroform) δ 8.78 (s, 1H), 8.27 (s, 1H), 7.75-7.37 (m, 3H), 7.38 (s, 1H), 7.38 (s, 1H), 7.28 (d, J = 15.0 Hz, 5H), 7.20-6.87 (m, 6H), 6.90 (s, 1H), 6.90 (s, 1H), 6.78 (s, 1H), 5.71 (s, 1H), 5.15(s, 1H), 5.06(s, 1H), 4.33(s, 2H), 3.80(s, 3H), 3.63(s, 1H), 3.50(s, 1H) ), 3.29(s, 2H), 3.04(s, 1H), 2.54(s, 1H), 2.22(s, 1H), 2.02(s, 2H), 1.91(s, 1H).

[0267] Example 192. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-methoxy-1H-indole-2-carboxamide (A192) 1 H NMR (500 MHz, chloroform) δ 8.78 (s, 1H), 8.27 (s, 1H), 7.75-7.37 (m, 3H), 7.38 (s, 1H), 7.38 (s, 1H), 7.28 (d, J = 15.0 Hz, 5H), 7.20-6.87 (m, 6H), 6.90 (s, 1H), 6.90 (s, 1H), 6.78 (s, 1H), 5.71 (s, 1H), 5. .15(s, 1H), 5.06(s, 1H), 4.33(s, 2H), 3.80(s, 3H), 3.63(s, 1H), 3.50(s, 1H), 3.29(s , 2H), 3.04(s, 1H), 2.54(s, 1H), 2.22(s, 1H), 2.02(s, 2H), 1.91(s, 1H), 1.27(s, 9H).

[0268] Example 193. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-methoxy-1H-indole-2-carboxamide (A193) 1 H NMR (500 MHz, chloroform) δ 8.68 (s, 1H), 8.12 (s, 1H), 7.59 (s, 1H), 7.45 (s, 1H), 7.16 (t, J = 12.5 Hz, 6H), 6.79 (s, 1H), 6.44 (s, 1H), 6.10 (s, 1H), 5.19 (s, 1H), 4.95 (s, 1H), 4.82 (s, 2H), 3.81 (s, 3H), 3.65 (s, 1H) , 3.54(s, 1H), 3.29(s, 1H), 3.04(s, 1H), 2.58(s, 2H), 2.21(d, J=16.4Hz, 2H), 2.02(s, 1H) , 1.88(d, J=41.9Hz, 3H), 1.80(s, 1H), 1.62(s, 2H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0269] Example 194. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-methoxy-1H-indole-2-carboxamide (A194) 1 H NMR (500 MHz, chloroform) δ 8.66 (s, 1H), 8.34 (s, 1H), 7.59 (s, 1H), 7.45 (s, 1H), 7.29 (d, J = 15.0 Hz, 5H), 7.24-6.99 (m, 7H), 6.79 (s, 1H), 5.90 (s, 1H), 5.04 (s, 1H), 4.72 (s, 1H), 4.34 (s, 2H). H), 3.81(s, 3H), 3.29(s, 1H), 3.21(d, J=15.0Hz, 2H), 3.04(s, 1H), 2.86(s, 1H) , 2.29(s, 1H), 2.11(s, 1H), 2.01(s, 21H), 1.90(d, J=11.7Hz, 1H), 1.52(s, 1H).

[0270] Example 195. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-methoxy-1H-indole-2-carboxamide (A195) 1 H NMR (500 MHz, chloroform) δ 8.46 (s, 1H), 7.57 (s, 1H), 7.43 (s, 1H), 7.17 (s, 1H), 7.12 (s, 4H), 7.00 (s, 1H), 6.92 (s, 1H), 6.77 (s, 1H), 6.49 (s, 1H), 5.75 (s, 1H), 5.20 (s, 1H), 4.67 (s, 1H), 3.80 ( s, 3H), 3.28(s, 1H), 3.20(d, J=15.0Hz, 2H), 3.03(s, 1H), 2.77(s, 1H), 2.40(s, 1H) ), 2.30(s, 1H), 2.00(s, 1H), 1.94(s, 41H), 1.90(s, 1H), 1.51(s, 1H), 1.27(s, 9H).

[0271] Example 196. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-5-methoxy-1H-indole-2-carboxamide (A196) 1H NMR (500 MHz, chloroform) δ 8.61 (s, 1H), 8.10 (s, 1H), 7.59 (s, 1H), 7.45 (s, 1H), 7.19 (d, J = 2.6 Hz, 2H), 7.14 (s, 4H), 6.72 (d, J = 66.4 Hz, 2H), 5.95 (s, 1H), 5.05 (s, 1H), 4.95 (s, 1H), 4.71 (s, 1H), 3.81 (s, 3H), 3.29 (s, 1H), 3.2 1(d, J=15.0Hz, 2H), 3.04(s, 1H), 2.86(s, 1H), 2.37(s, 61H), 2.21-2.17(m, 2H), 2.01(s, 1H), 1.90 (d, J=11.5Hz, 1H), 1.84(s, 2H), 1.62(s, 1H), 1.54(s, 1H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0272] Example 197. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A197) 1 H NMR (500 MHz, chloroform) δ 8.60 (s, 1H), 7.97 (s, 1H), 7.59 (s, 1H), 7.38 (s, 1H), 7.29 (d, J = 15.0 Hz, 5H), 7.16 (s, 1H), 7.10 (d, J = 9.2 Hz, 2H), 6.97 (s, 1H), 6.16 (s, 1H), 4.87 (s, 1H), 4. 67(s, 1H), 4.34(s, 2H), 3.65(s, 1H), 3.54(s, 1H), 2.61(s, 1H), 2.22(s, 1H), 2 .02(s, 1H), 1.92(s, 1H), 1.76(s, 1H), 1.11(s, 1H), 0.60(s, 1H), 0.35(s, 1H).

[0273] Example 198. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A198) 1 H NMR (500MHz, chloroform) δ 8.59(s, 1H), 7.98(s, 1H), 7.61(d, J=10.9Hz, 2H), 7.12(d, J=16.2Hz, 2 H), 6.98(s, 1H), 6.56(s, 1H), 6.12(s, 1H), 4.81(s, 1H), 4.67(s, 1H), 3. 65(s, 1H), 3.54(s, 1H), 2.59(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.92(s , 1H), 1.76(s, 1H), 1.27(s, 9H), 1.11(s, 1H), 0.58(s, 1H), 0.33(s, 1H).

[0274] Example 199. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A199) 1 H NMR (500 MHz, chloroform) δ 8.65 (s, 1H), 8.25 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.12 (d, J = 24.7 Hz, 2H), 7.10-7.07 (m, 1H), 6.98 (s, 1H), 6.41 (s, 1H), 6.15 (s, 1H), 4.82 (s, 1H), 4.58 (s, 1H), 3.66 (d, J = 5.6 Hz, 2H). H), 3.54(s, 1H), 2.59(s, 1H), 2.23(s, 1H), 2.02(s, 1H), 1.93(s, 1H), 1.75(d, J=10.0Hz, 3 H), 1.46(t, J=12.5Hz, 3H), 1.21(s, 2H), 1.11(d, J=0.5Hz, 2H), 0.57(s, 21H), 0.28(s, 1H).

[0275] Example 200. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A200) 1H NMR (500MHz, chloroform)δ 8.62(s, 1H), 8.00(d, J=20.6Hz, 2H), 7.60(s, 1H), 7.30(d, J=15.0Hz, 5H), 7.18(d, J= 6.9Hz, 2H), 7.10(s, 1H), 6.98(s, 1H), 6.09(s, 1H), 4.85(s, 1H), 4.33(d, J=13.7Hz, 3 H), 3.21(d, J=15.0Hz, 2H), 2.91(s, 1H), 2.62(s, 1H), 2.54(s, 1H), 2.01(s, 1H), 1.92 (d, J=12.0Hz, 1H), 1.76(s, 2H), 1.59(s, 1H), 1.11(s, 1H), 0.45(s, 1H), 0.13(s, 1H).

[0276] Example 201. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclobutyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A201) 1 H NMR (500MHz, chloroform)δ 7.98(s, 1H), 7.60(s, 1H), 7.29(d, J=15.0Hz, 5H), 7.10(s, 1H), 6.98(s, 1H), 4.34(s, 2H), 2.75(s, 1H), 2.67(s, 1H), 2.09(s , 1H), 2.03(d, J=6.8Hz, 4H), 1.94(s, 1H), 1.92-1.82(m, 3H), 1.76(s, 1H), 1.66(d, J=10.0Hz, 2H), 1.61(s, 1H), 0.45(s, 1H),

[0277] Example 202. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclobutyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A202) 1H NMR (500MHz, chloroform)δ 7.98(s, 1H), 7.60(s, 1H), 7.29(m, 3H), 7.10(s, 1H), 6.98(s, 1H), 6.29(m, 3H), 2.75(s, 1H), 2.67(s, 1H), 2.09(s, 2H), 2.03( d, J=6.8Hz, 3H), 1.94(s, 1H), 1.92-1.82(m, 3H), 1.76(s, 1H), 1.66(d, J=10.0Hz, 2H), 1.61(s, 1H), 1.27(s, 9H), 0.45(s, 1H)

[0278] Example 203. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclobutyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A203) 1 H NMR (500MHz, chloroform)δ 7.98(s, 1H), 7.60(s, 1H), 7.10(s, 1H), 6.98(s, 1H), 4.95(s, 1H), 2.7 4(s, 1H), 2.66(s, 1H), 2.19(s, 2H), 2.09(s, 1H), 2.03(d, J=6.9Hz, 2H) , 1.94(s, 1H), 1.86(dd, J=18.2, 10.2Hz, 5H), 1.76(s, 2H), 1.64(dd, J=22.9, 7.1Hz, 3H), 1.37(s, 1H), 1.31(s, 2H), 1.20(s, 2H), 0.45(s, 1H)

[0279] Example 204. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclobutyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A204) 1H NMR (500MHz, chloroform)δ 7.98(s, 1H), 7.60(s, 1H), 7.29(d, J=15.0Hz, 4H), 7.10(s, 1H), 6.98(s, 1H), 6.05(m, 2H), 4.34(s, 2H), 3.21(d, J=15.0) Hz, 2H), 2.09(s, 1H), 2.06-1.69(m, 9H), 1.76(s, 2H), 1.76(s, 2H), 1.65(s, 1H), 1.61(s, 1H), 0.53(s, 1H), 0.39(s, 1H).

[0280] Example 205. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclobutyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A205) 1 H NMR (500MHz, chloroform)δ 8.62(s, 1H), 8.00(d, J=20.6Hz, 2H), 7.60(s, 1H), 7.30(d, J=15.0Hz, 5H), 7.18(d, J=6. 9Hz, 2H), 7.10(s, 1H), 6.98(s, 1H), 6.09(s, 1H), 4.85(s, 1H), 4.33(d, J=13.7Hz, 3H), 3. 21(d, J=15.0Hz, 2H), 2.91(s, 1H), 2.62(s, 1H), 2.54(s, 1H), 2.01(s, 1H), 1.92(d, J=12. 0Hz, 1H), 1.76(s, 2H), 1.59(s, 1H), 1.27(s, 9H), 1.11(s, 3H), 0.45(s, 1H), 0.13(s, 1H).

[0281] Example 206. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclobutyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A206) 1H NMR (500MHz, chloroform)δ 8.62(s, 1H), 8.00(d, J=20.6Hz, 2H), 7.60(s, 1H), 7.30(d, J=15.0Hz, 5H), 7.18(d, J= 6.9Hz, 2H), 7.10(s, 1H), 6.98(s, 1H), 6.09(s, 1H), 4.85(s, 1H), 4.33(d, J=13.7Hz, 3 H), 3.21(d, J=15.0Hz, 2H), 2.91(s, 1H), 2.62(s, 1H), 2.54(s, 1H), 2.01(s, 1H), 1.92 (d, J=12.0Hz, 1H), 1.76(s, 2H), 1.59(s, 1H), 1.11(s, 1H), 0.45(s, 21H), 0.13(s, 1H).

[0282] Example 207. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A207) 1 H NMR (500 MHz, chloroform) δ 8.57 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.38 (s, 1H), 7.30 (d, J = 15.0 Hz, 5H), 7.13-7.07 (m, 2H), 6.98 (d, J = 4.1 Hz, 2H), 6.13 (s, 1H), 4.81 (d, J = 3.3 Hz, 1H), 4.34(s, 2H), 3.65(s, 1H), 3.55(s, 1H), 2.60(s, 1H), 2.22(s, 1H), 2.02(s, 1H) ), 1.92(s, 3H), 1.76(s, 3H), 1.66(d, J=4.7Hz, 3H), 1.36(s, 1H), 1.23(s, 1H).

[0283] Example 208. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A208) 1H NMR (500MHz, chloroform) δ 8.60(s, 1H), 7.98(s, 1H), 7.77(s, 1H), 7.60(s, 1H), 7.11(d, J=5.1Hz, 82 H), 6.98(s, 1H), 6.57(s, 1H), 6.14(s, 1H), 4.83(s, 1H), 4.61(s, 1H), 3.66 (s, 1H), 3.54(s, 1H), 2.59(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.93(s, 1H) , 1.76(s, 3H), 1.65(d, J=11.9Hz, 5H), 1.34(s, 4H), 1.26(d, J=8.6Hz, 9H).

[0284] Example 209. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A209) 1 H NMR (500 MHz, chloroform) δ 8.54 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.28 (s, 1H), 7.08 (d, J = 16.5 Hz, 2H), 6.98 (s, 1H), 6.46 (s, 1H), 6.14 (s, 1H), 4.80 (s, 1H), 4.75 (s, 1H), 3.64 (d, J = 19.8 Hz, 2H), 3.54 (s, 1H) , 2.59(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.93(s, 1H), 1.75(d, J=10.0Hz, 6H), 1.65(d, J= 6.5Hz, 63H), 1.46(t, J=12.5Hz, 4H), 1.35(s, 3H), 1.27(s, 1H), 1.21(s, 2H), 1.11(s, 1H).

[0285] Example 210. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A210) 1H NMR (500 MHz, chloroform) δ 8.51 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.30 (d, J = 15.0 Hz, 5H), 7.24 (s, 1H), 7.09 (d, J = 13.7 Hz, 2H), 6.98 (s, 1H), 6.89 (s, 1H), 6.11 (s, 1H), 4.79 (s, 1H), 4.65 (s, 11H), 4.34 (s, 2H), 3.21(d, J=15.0Hz, 2H), 2.91(s, 1H), 2.50(d, J=13.8Hz, 2H), 2.01(s, 1H), 1.92(d, J =5.3Hz, 1H), 1.76(s, 3H), 1.65(d, J=5.8Hz, 3H), 1.58(s, 1H), 1.36(s, 1H), 1.23(s, 1H).

[0286] Example 211. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A211) 1 H NMR (500 MHz, chloroform) δ 8.45 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.10 (s, 1H), 7.00 (d, J = 18.5 Hz, 2H), 6.89 (s, 1H), 6.53 (s, 1H), 6.10 (s, 1H), 4.78 (s, 1H), 4.65 (s, 1H), 3.21 (d, J = 15.0 Hz, 2H), 2 .90(s, 1H), 2.49(d, J=13.5Hz, 2H), 2.01(s, 1H), 1.91(d, J=1.6Hz, 1H), 1.76(s, 3H) , 1.63(t, J=21.9Hz, 4H), 1.55-1.52(m, 1H), 1.37(s, 1H), 1.27(s, 9H), 1.22(s, 1H).

[0287] Example 212. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A212) 1 H NMR (500 MHz, chloroform) δ 8.45 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.10 (s, 1H), 7.00 (d, J = 19.1 Hz, 42H), 6.88 (s, 1H), 6.44 (s, 1H), 6.10 (s, 1H), 4.95 (s, 1H), 4.77 (s, 1H), 4.64 (s, 1H), 3.21 (d, J = 15.0 Hz, 2H), 2.90 (s, 1H), 1.00 (d, J = 15.0 Hz, 2 ... H), 2.49(d, J=19.3Hz, 2H), 2.19(s, 2H), 2.01(s, 1H), 1.93-1.89(m, 1H), 1.84(s, 2H), 1.76(s, 3 H), 1.73-1.60(m, 6H), 1.57(s, 1H), 1.37(d, J=2.4Hz, 3H), 1.31(s, 1H), 1.21(d, J=13.0Hz, 2H).

[0288] Example 213. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,2-difluorobenzo[d][1,3]m-dioxole-5-carboxamide (A213) 1 H NMR (500 MHz, chloroform) δ 7.97 (s, 1H), 7.61 (s, 1H), 7.49 (s, 1H), 7.55-7.23 (m, 6H), 7.55-6.98 (m, 8H), 6.13 (s, 1H), 4.86 (s, 1H), 4.49 (s, 1H), 4.34 (s, 2H), 3.66 (s, 1H), 3.54 ( s, 1H), 2.59(s, 1H), 2.23(s, 1H), 2.02(s, 1H), 1.93(s, 1H), 1.80(s, 3H), 1 .69(d, J=10.0Hz, 3H), 1.31(s, 1H), 1.26(s, 1H), 1.11(s, 1H), 1.03(s, 1H).

[0289] Example 214. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,2-difluorobenzo[d][1,3]m-dioxole-5-carboxamide (A214) 1 H NMR (500MHz, chloroform)δ 7.73(s, 1H), 7.61(s, 1H), 7.49(s, 1H), 7.16(s, 1H), 6.52(s, 1H), 6.13(s, 1H), 4.83(s, 1H), 4.55(s, 1H), 3.66(s, 1H), 3.54(s, 1H), 2.58( s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.93(s, 1H), 1.80(s, 2H), 1.58(s, 1H), 1.51(d, J=15.0Hz, 3H), 1.48-1.41(m, 4H), 1.28(d, J=5.4Hz, 9H).

[0290] Example 215. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,2-difluorobenzo[d][1,3]m-dioxole-5-carboxamide (A215) 1 H NMR (500 MHz, chloroform) δ 7.55 (d, J = 60.0 Hz, 2H), 7.16 (d, J = 2.8 Hz, 2H), 6.45 (s, 1H), 6.14 (s, 1H), 4.95 (s, 1H), 4.77 (s, 1H), 4.66 (s, 1H), 3.66 (s, 1H), 3.54 (s, 1H), 2.58 (s, 1H), 2.21 (d, J = 17.0 Hz, 2H), H), 2.02(s, 1H), 1.92(s, 1H), 1.84(s, 2H), 1.80(s, 1H), 1.64(d, J=16.1Hz, 3H), 1.51( d, J=15.0Hz, 2H), 1.44(dd, J=12.8, 7.8Hz, 6H), 1.37(s, 3H), 1.31(s, 1H), 1.20(s, 2H).

[0291] Example 216. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,2-difluorobenzo[d][1,3]m-dioxole-5-carboxamide (A216) 1 H NMR (500 MHz, chloroform) δ 7.55 (d, J = 60.0 Hz, 2H), 7.46-7.26 (m, 6H), 7.16 (s, 1H), 7.09 (s, 1H), 6.08 (s, 1H), 4.79 (s, 1H), 4.41 (s, 1H), 4.34 (s, 2H), 3.21 (d, J = 15.0 Hz, 2H), 2.85 (s, 1H ), 2.53(d, J=12.1Hz, 2H), 2.01(s, 1H), 1.91(d, J=3.6Hz, 1H), 1.80(s, 1H), 1.7 2(s, 1H), 1.58(s, 1H), 1.52(d, J=15.0Hz, 2H), 1.48-1.41(m, 4H), 1.34(s, 1H).

[0292] Example 217. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,2-difluorobenzo[d][1,3]m-dioxole-5-carboxamide (A217) 1 H NMR (500MHz, chloroform)δ 7.61(s, 2H), 7.49(s, 2H), 7.16(s, 2H), 6.89(s, 2H), 6.53(s, 2H), 6.09(s, 2H) ), 4.76(s, 1H), 4.44(s, 1H), 3.21(d, J=15.0Hz, 4H), 2.88(s, 2H), 2.49(d, J=3 .0Hz, 4H), 2.01(s, 1H), 1.93-1.89(m, 2H), 1.80(s, 3H), 1.69(d, J=10.0Hz, 2H ), 1.57(s, 1H), 1.31(d, J=4.8Hz, 2H), 1.27(s, 9H), 1.11(s, 1H), 1.03(s, 3H).

[0293] Example 218. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,2-difluorobenzo[d][1,3]m-dioxole-5-carboxamide (A218) 1 H NMR (500MHz, chloroform)δ 7.58(s, 1H), 7.46(s, 1H), 7.13(s, 1H), 6.47(d, J=5.5Hz, 2H), 5.81(s, 1H), 4.93(d, J=6.0Hz , 2H), 4.37(s, 1H), 3.34(s, 1H), 3.20(d, J=15.0Hz, 2H), 2.37(d, J=18.2Hz, 2H), 2.18(s, 2H), 2.00(s, 1H), 1.90(d, J=0.5Hz, 1H), 1.81(d, J=19.9Hz, 6H), 1.69(s, 2H), 1.64(d, J=29.9Hz, 3 H), 1.51(s, 1H), 1.37(s, 3H), 1.31(s, 2H), 1.18(d, J=16.6Hz, 3H), 1.11(s, 1H), 1.03(s, 2H).

[0294] Example 219. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,2-difluorobenzo[d][1,3]m-dioxole-5-carboxamide (A219) 1H NMR (500MHz, chloroform)δ 7.58(s, 1H), 7.46(s, 1H), 7.13(s, 1H), 6.47(d, J=5.5Hz, 2H), 5.81(s, 1H), 4.93(d, J=6.0Hz , 2H), 4.37(s, 1H), 3.34(s, 1H), 3.20(d, J=15.0Hz, 2H), 2.37(d, J=18.2Hz, 2H), 2.18(s, 2H), 2.00(s, 1H), 1.90(d, J=0.5Hz, 1H), 1.81(d, J=19.9Hz, 6H), 1.69(s, 2H), 1.64(d, J=29.9Hz, 3 H), 1.51(s, 1H), 1.37(s, 3H), 1.31(s, 2H), 1.18(d, J=16.6Hz, 3H), 1.11(s, 1H), 1.03(s, 2H).

[0295] Example 220. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dimethoxy-1H-indole-2-carboxamide (A220) 1 H NMR (500MHz, chloroform) δ 9.90(s, 1H), 8.66(s, 1H), 8.26(s, 1H), 7.77(s, 1H), 7.30(d, J=15.0Hz, 5 H), 7.23-7.03(m, 6H), 6.71(s, 1H), 6.26(s, 1H), 5.98(s, 1H), 5.15(s, 1H) ), 4.87(s, 1H), 4.34(s, 2H), 3.79(s, 6H), 3.64(s, 1H), 3.52(s, 1H), 3.29 (s, 1H), 3.04(s, 1H), 2.52(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.92(s, 2H).

[0296] Example 221. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dimethoxy-1H-indole-2-carboxamide (A221) 1H NMR (500 MHz, chloroform) δ 8.60(s, 1H), 8.35(s, 1H), 7.76(s, 1H), 7.17(d, J=25.0 Hz, 5H), 6.69(s, 1H), 6.58(s, 1H), 6.23(s, 1H), 6.00(s, 1H), 5.18(s, 1H), 4.81(s, 1H), 3.79(s, 6H), 3.64(s, 1H), 3.53(s, 1H), 3.29(s, 1H), 3.04(s, 1H), 2.55(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.92(s, 1H), 1.27(s, 9H).

[0297] Example 222. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dimethoxy-1H-indole-2-carboxamide (A222) 1 H NMR (500 MHz, chloroform) δ 8.59 (s, 1H), 8.10 (s, 1H), 7.68 (s, 1H), 7.15 (d, J = 25.0 Hz, 5H), 6.67 (s, 1H), 6.45 (s, 1H), 6.21 (s, 1H), 6.07 (s, 1H), 5.18 (s, 1H), 4.94 (s, 1H), 4.80 (s, 1H), 3.78 (s, 6H), 3.64 (s, 1H) , 3.53(s, 1H), 3.28(s, 1H), 3.03(s, 1H), 2.56(s, 1H), 2.20(d, J=16.3Hz, 3H), 2.02(s, 1H) , 1.88(d, J=41.4Hz, 3H), 1.80(s, 1H), 1.62(s, 1H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0298] Example 223. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dimethoxy-1H-indole-2-carboxamide (A223) 1H NMR (500 MHz, chloroform) δ 8.65 (s, 1H), 8.29 (s, 1H), 8.02 (s, 1H), 7.27 (d, J = 15.0 Hz, 5H), 7.14 (d, J = 24.9 Hz, 5H), 6.92 (s, 1H), 6.59 (s, 1H), 6.20 (s, 1H), 6.08 (s, 1H), 5.01 (s, 1H), 4.76 (s, 1H) ), 4.33(s, 2H), 3.78(s, 6H), 3.28(s, 1H), 3.20(d, J=15.0Hz, 2H), 3.03(s, 1H), 2. 85(d, J=1.0Hz, 2H), 2.32(s, 1H), 2.00(s, 1H), 1.90(d, J=1.3Hz, 1H), 1.61(s, 1H).

[0299] Example 224. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dimethoxy-1H-indole-2-carboxamide (A224) 1 H NMR (500 MHz, chloroform) δ 8.80 (d, J = 11.2 Hz, 2H), 7.09 (t, J = 61.7 Hz, 6H), 6.94 (s, 1H), 6.94 (s, 1H), 6.77 (s, 1H), 6.63 (s, 1H), 6.56 (s, 1H), 5.04 (d, J = 1.0 Hz, 2H), 4.99 (s, 1H), 3.79 (s, 6H), 3.2 9(s, 1H), 3.21(d, J=15.0Hz, 3H), 2.93(d, J=106.3Hz, 2H), 2.79-2.70(m, 1H), 2.40 (s, 1H), 2.27(s, 1H), 2.01(s, 1H), 1.92(d, J=8.4Hz, 1H), 1.46(s, 1H), 1.27(s, 9H).

[0300] Example 225. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4,6-dimethoxy-1H-indole-2-carboxamide (A225) 1H NMR (500 MHz, chloroform) δ 8.67 (s, 1H), 7.80 (s, 1H), 7.65 (s, 1H), 7.08 (t, J = 67.3 Hz, 6H), 6.91 (s, 1H), 6.91 (s, 1H), 6.55 (s, 1H), 6.49 (s, 1H), 6.07 (s, 1H), 5.09 (s, 1H), 4.95 (s, 1H), 4.69 (s, 1H), 3.79 (s, 6H), 3.29 (s, 1H), 3.21(d, J=15.0Hz, 2H), 3.04(s, 1H), 2.93(s, 1H), 2.42(d, J=15.8Hz, 2H), 2.19(s, 2H), 2.03-1.73 (m, 5H), 1.84(s, 3H), 1.84(s, 2H), 1.60(d, J=16.9Hz, 2H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0301] Example 226. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A226) 1 H NMR (500MHz, chloroform)δ 8.76(s, 1H), 8.12(s, 1H), 7.98(s, 1H), 7.89(s, 1H), 7.60(s, 1H), 7.29(d, J=15 .0Hz, 5H), 7.19(d, J=17.1Hz, 2H), 7.10(d, J=2.2Hz, 2H), 6.99(d, J=15.0Hz, 2H) , 6.31(s, 1H), 5.05(s, 1H), 4.91(s, 1H), 4.34(s, 2H), 3.67(s, 1H), 3.56(s, 1H) , 3.29(s, 1H), 3.04(s, 1H), 2.70(s, 1H), 2.23(s, 1H), 2.02(s, 2H), 1.93(s, 1H).

[0302] Example 227. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A227) 1 H NMR (500 MHz, chloroform) δ 8.72 (s, 1H), 8.44 (s, 1H), 7.96 (s, 1H), 7.59 (s, 1H), 7.25 (s, 1H), 7.16 (s, 1H), 7.09 (d, J = 2.1 Hz, 2H), 6.98 (d, J = 15.0 Hz, 2H), 6.60 (s, 1H), 5.97 (s, 1H), 5.06 (s, 1H), 5.04 (s, 1H), 5.09 (s, 1H), 5.04 ... H), 5.12(s, 1H), 4.82(s, 1H), 3.64(s, 1H), 3.52(s, 1H), 3.28(s, 1H), 3.03 (s, 1H), 2.54(s, 1H), 2.22(s, 1H), 2.02(s, 1H), 1.92(s, 1H), 1.27(s, 9H).

[0303] Example 228. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A228) 1 H NMR (500 MHz, chloroform) δ 8.69 (s, 1H), 8.41 (s, 1H), 7.94 (s, 1H), 7.56 (s, 1H), 7.23 (s, 1H), 7.13 (s, 1H), 7.06 (d, J = 0.9 Hz, 2H), 6.96 (d, J = 14.9 Hz, 2H), 6.65 (s, 1H), 5.95 (s, 1H), 5.11 (s, 1H), 4.92 (s, 1H), 4.81 (s, 1H), 3.63(s, 1H), 3.51(s, 1H), 3.27(s, 1H), 3.02(s, 1H), 2.53(s, 1H), 2.19(d, J=14.6Hz, 2H), 2.01( s, 1H), 1.87(d, J=40.1Hz, 3H), 1.79(s, 1H), 1.61(s, 1H), 1.36(s, 2H), 1.30(s, 1H), 1.19(s, 2H).

[0304] Example 229. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A229) 1 H NMR (500 MHz, chloroform) δ 8.69 (s, 1H), 8.11 (s, 1H), 7.95 (s, 1H), 7.57 (s, 1H), 7.43 (s, 1H), 7.27 (d, J = 15.0 Hz, 5H), 7.14 (s, 1H), 7.07 (s, 1H), 6.97 (d, J = 15.0 Hz, 2H), 6.82 (s, 1H), 6.58 (s, 1H), 6.04 (s, 1H), 5.01(s, 21H), 4.83(s, 1H), 4.32(s, 2H), 3.28(s, 1H), 3.20(d, J=15.0Hz, 2H), 3.03(s, 1H) , 2.89(s, 1H), 2.70(s, 1H), 2.25(s, 1H), 2.00(s, 1H), 1.90(d, J=2.9Hz, 1H), 1.60(s, 1H).

[0305] Example 230. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A230) 1 H NMR (500 MHz, chloroform) δ 8.74 (s, 1H), 8.06 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.17 (s, 1H), 7.11 (d, J = 8.4 Hz, 2H), 7.03-6.90 (m, 3H), 6.53 (s, 1H), 5.75 (s, 1H), 5.12 (s, 1H), 4.72 (s, 1H) ), 3.29(s, 1H), 3.21(d, J=15.0Hz, 2H), 3.04(s, 1H), 2.75(s, 1H), 2.43(s, 1H), 2.33(s, 1H), 2.01(s, 1H), 1.96(s, 1H), 1.91(s, 1H), 1.52(s, 1H), 1.27(s, 9H).

[0306] Example 231. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A231) 1 H NMR (500 MHz, chloroform) δ 8.72 (s, 1H), 7.99 (d, J = 25.5 Hz, 2H), 7.59 (s, 1H), 7.16 (s, 1H), 7.09 (d, J = 4.0 Hz, 2H), 6.97 (t, J = 11.7 Hz, 3H), 6.45 (s, 1H), 6.07 (s, 1H), 5.09 (s, 1H), 4.94 (s, 1H), 4.68 (s, 1H), 3.28 (s, 1H), 3.2 1(d, J=15.0Hz, 2H), 3.03(s, 1H), 2.95(s, 1H), 2.44(d, J=17.0Hz, 2H), 2.19(s, 2H), 2.03-1.73( m, 5H), 1.84(s, 2H), 1.84(s, 2H), 1.60(d, J=13.6Hz, 2H), 1.37(s, 2H), 1.31(s, 1H), 1.20(s, 2H).

[0307] Example 232. N-((S)-1-(((S)-4-(benzyl)-3,4-dione-1-(isopropylamino)o-2-yl)amino)-3-(cyclohexyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A232) 1H NMR (500 MHz, chloroform) δ 8.57 (s, 1H), 7.94 (s, 1H), 7.57 (s, 1H), 7.40 (s, 1H), 7.26 (d, J = 14.9 Hz, 4H), 7.16-7.03 (m, 3H), 6.95 (s, 1H), 6.45 (s, 1H), 5.67 (s, 1H), 4.95 (s, 1H), 4.48 (s, 1H), 4.32 (s , 2H), 3.79(s, 1H), 2.20(s, 1H), 2.15(s, 1H), 2.04(s, 2H), 1.77(d, J=19.9Hz, 3H), 1. 68(d, J=10.0Hz, 4H), 1.37(s, 1H), 1.30(s, 1H), 1.11(s, 1H), 1.01(d, J=14.9Hz, 6H).

[0308] Example 233. N-((S)-1-(((S)-4-(benzyl)-3,4-dione-1-(isopropylamino)o-2-yl)amino)-3-(phenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A233) 1 H NMR (500MHz, chloroform) δ 8.85(s, 1H), 8.41(s, 1H), 7.98(s, 1H), 7.60(s, 1H), 7.29(d, J=15.0Hz, 5 H), 7.20(d, J=16.0Hz, 2H), 7.12(d, J=20.0Hz, 5H), 6.98(s, 1H), 6.69(s, 1H), 5.05(s, 1H), 5.01(s, 1H), 4.74(s, 1H), 4.34(s, 2H), 3.81(s, 1H), 3. 29(s, 2H), 3.04(s, 1H), 2.21(d, J=5.4Hz, 2H), 2.05(s, 2H), 1.00(s, 6H).

[0309] Example 234. N-((S)-1-(((S)-4-(cyclohexyl)-3,4-dione-1-(isopropylamino)o-2-yl)amino)-3-(phenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A234) 1H NMR (500 MHz, chloroform) δ 8.73 (s, 1H), 8.16 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.27 (s, 1H), 7.19 (s, 1H), 7.12 (d, J = 20.0 Hz, 5H), 7.07 (s, 1H), 6.98 (s, 1H), 6.53 (s, 1H), 5.87 (s, 1H), 5.64 (s, 1H), 4.92 (s, 1H), 4.86 (s, 1H), 5.87 (s, 1H), 5.64 ...5.87 (s, 1H), 5.64 (s, 1H), 5.87 (s, 1H), 5.64 (s, 1H), 5.87 (s, 1H), 5.64 (s, 1H), 5.87 (s, 1H), 5.64 (s, 1H), 5.87 (s, 1H), 5.64 H), 3.81(s, 1H), 3.29(s, 3H), 3.02(d, J=18.8Hz, 3H), 2.19(d, J=11.4Hz, 2H), 2.05(s, 2H), 1.80 (s, 1H), 1.69(d, J=10.0Hz, 3H), 1.58(s, 1H), 1.31(s, 1H), 1.11(s, 1H), 1.01(d, J=15.0Hz, 8H).

[0310] Example 235. N-((S)-1-(((S)-4-(cyclohexyl)-3,4-dione-1-(cyclohexylamino)o-2-yl)amino)-3-(phenyl)-1-oxopropan-2-yl)-1H-indole-2-carboxamide (A235) 1 H NMR (500 MHz, chloroform) δ 8.73 (s, 1H), 8.14 (s, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.26 (s, 1H), 7.19 (s, 1H), 7.12 (d, J = 20.0 Hz, 5H), 6.98 (s, 1H), 6.56 (s, 1H), 5.90 (s, 1H), 5.63 (s, 1H), 4.93 (d, J = 16.9 Hz, 2H), 4.86 (s, 1H), 3.29 ( s, 1H), 3.02(d, J=18.8Hz, 3H), 2.23-2.14(m, 4H), 2.05(s, 2H), 1.82(d, J=20.0Hz, 4H), 1.69(d, J=1 0.0Hz, 3H), 1.62(s, 1H), 1.37(d, J=0.9Hz, 3H), 1.31(s, 3H), 1.20(s, 2H), 1.11(s, 1H), 1.03(s, 2H).

[0311] Example 236. N-((S)-1-(((S)-4-(benzyl)-3,4-dione-1-(isopropylamino)o-2-yl)amino)-3-(cyclohexyl)-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A236) 1 H NMR (500MHz, chloroform)δ 9.45(s, 1H), 7.80(s, 2H), 7.67(s, 2H), 7.35-7.26(m, 6H), 7.11(s, 1H) ), 6.67(s, 1H), 5.75(s, 1H), 5.11(s, 1H), 4.33(d, J=6.4Hz, 3H), 3.81( s, 1H), 2.16(d, J=10.5Hz, 2H), 2.05(s, 1H), 1.76(s, 1H), 1.60(s, 1H), 1.51(d, J=15.0Hz, 2H), 1.48-1.41(m, 4H), 1.32(s, 1H), 1.00(s, 6H).

[0312] Example 237. N-((S)-1-(((S)-4-(cyclohexyl)-3,4-dione-1-(isopropylamino)o-2-yl)amino)-3-(cyclohexyl)-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A237) 1 H NMR (500 MHz, chloroform) δ 9.32 (s, 1H), 8.17 (s, 1H), 8.12 (s, 1H), 7.76 (s, 1H), 7.66 (d, J = 4.6 Hz, 2H), 7.33-7.27 (m, 4H), 7.19 (s, 1H), 5.70 (s, 1H), 4.93 (s, 1H), 4.80 (s, 1H), 4.75 (s, 1H), 4.03 (s, 1H), 3.98 (s, 1H), 3.24 ( s, 1H), 3.02-2.98(m, 3H), 2.30-2.26(m, 2H), 2.18(s, 1H), 2.10(s, 1H), 1.82-1.75(m, 2H), 1.75- 1.71(m, 2H), 1.67(s, 1H), 1.45-1.41(m, 2H), 1.33(s, 1H), 1.30-1.20(m, 6H), 1.14-1.07(m, 3H).

[0313] Example 238. N-((S)-1-(((S)-4-(benzyl)-3,4-dione-1-(isopropylamino)o-2-yl)amino)-3-(phenyl)-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A238) 1 H NMR (500 MHz, chloroform) δ 9.34 (s, 1H), 8.08 (d, J = 10.7 Hz, 2H), 7.62 (d, J = 0.9 Hz, 2H), 7.30-7.21 (m, 8H), 7.19 (s, 1H), 7.14 (s, 1H), 6.23 (s, 1H), 6.03 (s, 1H), 5.22 (s, 1H), 5.08 (s, 1H) , 4.95(s, 1H), 4.88(s, 1H), 4.33(s, 1H), 4.28(s, 1H), 3.96(s, 1H), 3.22(s, 1H) , 2.99(s, 1H), 2.38-2.34(m, 2H), 2.21(s, 1H), 2.16(s, 1H), 1.33-1.20(m, 6H).

[0314] Example 239. N-((S)-1-(((S)-4-(benzyl)-3,4-dione-1-(cyclohexylamino)o-2-yl)amino)-3-(phenyl)-1-oxopropan-2-yl)-quinoxaline-2-carboxamide (A239) 1 H NMR (500 MHz, chloroform) δ 9.31 (s, 1H), 8.12 (d, J = 31.2 Hz, 2H), 7.73 (s, 1H), 7.63 (d, J = 6.0 Hz, 2H), 7.36-7.24 (m, 8H), 7.17 (d, J = 11.8 Hz, 2H), 6.32 (s, 1H), 5.10 (s, 1H), 4.76 (s, 1H), 4.67 (s, 1H), 4.3 6(s, 1H), 4.30(d, J=18.6Hz, 2H), 4.12(s, 1H), 3.24(s, 1H), 2.97(s, 1H), 2.31-2.27(m , 2H), 2.12(d, J=3.2Hz, 2H), 1.94-1.87(m, 2H), 1.73-1.63(m, 4H), 1.61-1.55(m, 4H).

[0315] Example 240. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-indole-6-fluoro-2-carboxamide (A240) 1 H NMR (500MHz, chloroform)δ 8.12(s, 1H), 7.57(s, 1H), 7.52(s, 1H), 7.36-7.25(m, 4H), 7.20(d, J=7.7Hz, 2H), 6.84( s, 1H), 6.18(s, 1H), 5.49(d, J=11.0Hz, 2H), 4.70(s, 1H), 4.39(d, J=17.7Hz, 2H), 4.08( s, 1H), 3.24(d, J=17.5Hz, 2H), 2.54(s, 1H), 2.08-2.04(m, 2H), 1.82(s, 1H), 1.78-1.67 (m, 6H), 1.66-1.62(m, 2H), 1.58(dd, J=9.5, 3.3Hz, 5H), 1.44(s, 1H), 1.37-1.27(m, 3H).

[0316] Example 241. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-methyloxazole-2-carboxamide (A241) 1 H NMR (500 MHz, chloroform) δ 7.33-7.27 (m, 4H), 7.23 (s, 1H), 6.79 (d, J = 13.7 Hz, 2H), 6.29 (s, 1H), 6.09 (s, 1H), 5.05 (s, 1H), 4.99 (d, J = 9.8 Hz, 2H), 4.41 (s, 1H), 4.34 (s, 1H), 3.24 (d, J=14.9Hz, 2H), 2.92(s, 1H), 2.36-2.32(m, 3H), 2.08-2.04(m, 2H), 1.8 5(s, 1H), 1.79(s, 1H), 1.74-1.55(m, 11H), 1.48(s, 1H), 1.46-1.23(m, 3H).

[0317] Example 242. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-methyloxazole-2-carboxamide (A242) 1 H NMR (500 MHz, chloroform) δ 7.33-7.30 (m, 22H), 7.28 (t, J = 15.0 Hz, 33H), 6.83 (s, 9H), 6.14 (s, 9H), 6.09 (s, 9H), 5.94 (s, 9H), 5.19 (s, 9H), 5.01 (s, 9H), 4.36 (d, J = 0.5 Hz, 18H), 3.45 (s, 9H), 3.35 (s, 7H), 2.59 ( s, 9H), 2.38-2.34(m, 27H), 2.18(s, 8H), 2.09-2.05(m, 18H), 1.96-1.88(m, 24H), 1.88(s, 3 H), 1.73-1.60(m, 46H), 1.40-1.36(m, 16H), 1.32(s, 9H), 1.15(s, 7H), 1.12-1.08(m, 17H).

[0318] Example 243. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzo[d]1,3-dioxole-5-carboxamide (A243) 1H NMR (500 MHz, chloroform) δ 7.54 (s, 6H), 7.45 (s, 6H), 7.29-7.18 (m, 30H), 6.96 (s, 6H), 6.49 (s, 6H), 6.01 (s, 6H), 5.92-5.88 (m, 12H), 5.58 (s, 6H), 5.11 (s, 6H), 4.93 (s, 6H), 4.63 (s, 6H), 4.29 (s, 6H), 4.24 (s, 6H), 3.24 (d, J = 17.5 Hz, 11H) , 2.86(s, 6H), 2.05(t, J=4.2Hz, 18H), 1.95-1.87(m, 12H), 1.84(s, 6H), 1.76(t, J=4.8Hz, 17H), 1.63(dd, J=40.8, 34.9Hz, 22H), 1.51(dd, J=4.6, 1.3Hz, 1H), 1.40-1.36(m, 10H), 1.32(s, 6H), 1.17-1.09(m, 17H).

[0319] Example 244. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-1H-benzo[d]imidazole-2-carboxamide (A244) 1 H NMR (500 MHz, chloroform) δ 7.84 (s, 1H), 7.73 (s, 1H), 7.62 (s, 1H), 7.38 (s, 1H), 7.31-7.23 (m, 6H), 7.16 (s, 1H), 6.17 (s, 1H), 5.59 (s, 1H), 5.10 (s, 1H), 4.75 (s, 1H), 4.53 (s, 1H), 4.36 (d, J = 17.3 Hz, 2H). 3.24(d, J=17.5Hz, 2H), 2.88(s, 1H), 2.06(t, J=2.7Hz, 3H), 1.96-1.81(m, 3H), 1.77(s, 1H), 1.73-1.60(m, 5H), 1.53(s, 1H), 1.40-1.36(m, 2H), 1.32(s, 1H), 1.22-1.15(m, 3H).

[0320] Example 245. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-7-methoxy-benzofuran-2-carboxamide (A245) 1 H NMR (500MHz, chloroform)δ 7.60(s, 8H), 7.34-7.22(m, 33H), 7.15(d, J=10.0Hz, 16H), 7.06(s, 8H), 6.81(s, 8H), 6.54(s, 8H), 6.22 (s, 8H), 5.59(s, 8H), 5.08(s, 8H), 4.92(s, 8H), 4.63(s, 8H), 4.32(d, J=1.1Hz, 16H), 3.89-3.85(m, 24H) , 3.24(d, J=17.4Hz, 15H), 2.94(s, 8H), 2.07(t, J=5.1Hz, 23H), 1.93-1.85(m, 18H), 1.84(s, 6H), 1.78( s, 6H), 1.73-1.51(m, 49H), 1.51(d, J=5.5Hz, 1H), 1.40-1.36(m, 14H), 1.32(s, 8H), 1.16-1.07(m, 23H).

[0321] Example 246. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-methyl-benzofuran-2-carboxamide (A246) 1H NMR (500MHz, chloroform)δ 7.60-7.40(m, 3H), 7.32-7.18(m, 7H), 6.67(s, 1H), 5.57(s, 1H), 5.15(s, 1H), 4 .67(s, 1H), 4.55(s, 1H), 4.30(d, J=14.7Hz, 2H), 3.24(d, J=17.3Hz, 2H), 2.73(s , 1H), 2.15-2.10(m, 4H), 2.08-2.04(m, 2H), 1.88-1.81(m, 3H), 1.77(s, 1H), 1.7 3-1.59(m, 5H), 1.55(s, 1H), 1.40-1.36(m, 2H), 1.32(s, 1H), 1.14-1.05(m, 3H).

[0322] Example 247. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3,5-dimethyl-benzofuran-2-carboxamide (A247) 1 H NMR (500 MHz, chloroform) δ 7.50-7.34 (m, 3H), 7.32-7.26 (m, 4H), 7.23 (s, 1H), 7.11 (s, 1H), 6.68 (s, 1H), 5.57 (s, 1H), 5.15 (s, 1H), 4.69 (s, 1H), 4.55 (s, 1H), 4.30 (d, J = 14.8 Hz, 2H), 3.24 (d, J = 17.3 Hz, 2H), 2.7 3(s, 1H), 2.45-2.41(m, 3H), 2.15-2.10(m, 4H), 2.08-2.04(m, 2H), 1.88-1.81(m, 3H), 1.77 (s, 1H), 1.73-1.59(m, 5H), 1.55(s, 1H), 1.40-1.36(m, 2H), 1.32(s, 1H), 1.14-1.05(m, 3H).

[0323] Example 248. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,7-dimethoxy-benzofuran-2-carboxamide (A248) 1 H NMR (500 MHz, chloroform) δ 7.59 (s, 1H), 7.34-7.27 (m, 2H), 7.27-7.22 (m, 2H), 7.10 (s, 1H), 6.86 (s, 1H), 6.82 (s, 1H), 6.38 (s, 1H), 6.32 (s, 1H), 5.56 (s, 1H), 5.35 (s, 1H), 4.66 (d, J = 18.6 Hz, 2H), 4.28 (s, 1H), 4.17 (s, 1H), 3.91-3.87 (m, 3H) ), 3.85-3.81(m, 3H), 3.24(d, J=17.8Hz, 2H), 3.06(s, 1H), 2.05(t, J=6.8Hz, 3H), 1.96-1.88(m, 2H), 1.84 (s, 1H), 1.77(s, 1H), 1.73-1.54(m, 5H), 1.52(s, 1H), 1.40-1.36(m, 2H), 1.32(s, 1H), 1.17-1.08(m, 3H).

[0324] Example 249. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-3-carboxamide (A249) 1 H NMR (500MHz, chloroform)δ 8.07(s, 91H), 7.62(s, 92H), 7.58(s, 94H), 7.47(s, 94H), 7.27(dd, J=9.9, 8.1Hz, 379H), 7.20(t, J=5.8Hz, 274H), 6.24(s, 91H), 5.61(s, 91H), 5.16(s, 90H), 4.93(s, 91H), 4.52(s, 89H), 4.32(d, J=0.6Hz, 182H), 3. 24(d, J=17.5Hz, 174H), 2.89(s, 93H), 2.06(t, J=2.7Hz, 257H), 1.92-1.80(m, 277H), 1.81(s, 7H), 1.77(s, 70H), 1.73-1.51(m, 541H), 1.51(d, J=1.8Hz, 6H), 1.40-1.36(m, 160H), 1.32(s, 86H), 1.22-1.16(m, 264H).

[0325] Example 250. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-6-chloro-2H-chromene-3-carboxamide (A250) 1 H NMR (500MHz, chloroform)δ 8.16(s, 1H), 7.32(s, 1H), 7.32-7.24(m, 4H), 7.23-7.09(m, 3H), 6.84(s, 1H), 6.05(s, 1H), 5.64(s, 1H), 5.33(s, 1H), 5.06-5.02(m, 2H), 4.50(d, J=9.3Hz, 2H), 4.39(s, 1H), 4.32(s, 1H), 3.24(d, J=17 .4Hz, 2H), 2.99(s, 1H), 2.15(s, 1H), 2.08-2.04(m, 2H), 1.85(s, 1H), 1.79(s, 1H), 1.73-1.69(m, 2H) ), 1.69-1.62(m, 5H), 1.55(s, 1H), 1.39-1.35(m, 2H), 1.31(s, 1H), 1.23-1.19(m, 2H), 1.17(s, 1H).

[0326] Example 251. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-6-chloro 2,3-dihydrobenzo[b]1,4-dioxine-6-carboxamide (A251) 1H NMR (500 MHz, chloroform) δ 8.51 (s, 1H), 7.66 (s, 1H), 7.55 (s, 1H), 7.11 (s, 1H), 5.40 (s, 1H), 5.16 (s, 1H), 4.65 (s, 1H), 4.52 (s, 1H), 4.38-4.34 (m, 4H), 3.45 (s, 1H), 3.36 (d, J = 13.4 Hz, 2H), 2.68 (s, 1H), 2.18 (s , 1H), 2.11-2.02(m, 2H), 1.99-1.84(m, 3H), 1.78-1.72(m, 2H), 1.71-1.62(m, 5H), 1.58(dd , J=9.0, 3.3Hz, 5H), 1.55-1.50(m, 2H), 1.48(s, 1H), 1.43-1.39(m, 4H), 1.37-1.29(m, 3H).

[0327] Example 252. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-phenyl-1-oxopropan-2-yl)-6-chloro 2,3-dihydrobenzo[b]1,4-dioxine-6-carboxamide (A252) 1 H NMR (500 MHz, chloroform) δ 9.01 (s, 1H), 7.52 (s, 1H), 7.29-7.23 (m, 2H), 7.23-7.17 (m, 2H), 7.15 (s, 1H), 7.04 (s, 1H), 6.92 (s, 1H), 6.21 (s, 1H), 5.12 (s, 1H), 5.05 (s, 1H), 4.87 (s, 1H), 4.52 (s, 1H), 4.38-4.34 (m, 4H), 3 .44(d, J=12.5Hz, 2H), 3.37-3.20(m, 3H), 2.98(s, 1H), 2.19(s, 1H), 2.12-2.04(m, 2H), 1.92(s , 1H), 1.85-1.78(m, 2H), 1.66(s, 1H), 1.56-1.52(m, 2H), 1.48-1.39(m, 3H), 1.23-1.11(m, 2H).

[0328] Example 253. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-methoxyindole-6-carboxamide (A253) 1 H NMR (500MHz, chloroform)δ 8.73(s, 5H), 8.50(s, 5H), 7.45(s, 5H), 7.37(s, 5H), 7.18(s, 5H), 6.75(s, 5H), 6.03(s, 5H), 5. 67(s, 5H), 5.61(s, 5H), 4.89(s, 5H), 4.57(s, 5H), 3.84-3.80(m, 15H), 3.43(d, J=16.9Hz, 10H), 3.35(s, 4H), 2.70(s, 5H), 2.19(s, 5H), 2.09-2.06(m, 9H), 2.06-2.04(m, 1H), 2.06-1.91(m, 16H) ), 1.73-1.61(m, 35H), 1.60-1.46(m, 47H), 1.46-1.39(m, 11H), 1.35-1.26(m, 9H), 1.22(s, 4H).

[0329] Example 254. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-4 fluorophenyl-1-oxopropan-2-yl)-5-methyl-benzofuran-2-carboxamide (A254) 1H NMR (500MHz, chloroform-d)δ 8.35(d, J=9.7Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.83(d, J=9.3Hz, 1H), 7.68(d, J=2.1Hz, 1H), 7.60(dd, J=2.7, 1.8Hz, 1H), 7. 41(d, J=8.2Hz, 1H), 7.35-7.22(m, 7H), 7.22-7.17(m, 1H), 7.07-7.00(m, 2H), 6.26(t, J=4.0Hz, 1H), 4.75(dt, J=9.7, 6.2Hz , 1H), 4.54-4.46(m, 1H), 4.50-4.45(m, 1H), 4.47(t, J=0.9Hz, 1H), 3.27-3.14(m, 2H), 3.08(ddt, J=6.2, 2.9, 1.1Hz, 2H), 2. 61 (tdd, J=8.9, 6.9, 4.3Hz, 1H), 2.13 (ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99 (ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.81-1.61 (m, 4H).

[0330] Example 255. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-chloro-benzofuran-2-carboxamide (A255) 1 H NMR (500MHz, chloroform) δ 7.75(s, 1H), 7.58(s, 1H), 7.49(s, 1H), 7.29(d, J=15.0Hz, 6H), 7.21(s , 1H), 6.10(s, 1H), 4.78(s, 1H), 4.52(s, 1H), 4.34(s, 2H), 3.21(d, J=15 .0Hz, 2H), 2.91(s, 1H), 2.53(d, J=13.0Hz, 2H), 2.01(s, 1H), 1.91(d, J =6.4Hz, 1H), 1.76(s, 1H), 1.64(s, 1H), 1.58(s, 1H), 1.55-1.37(m, 9H).

[0331] Example 256. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-chloro-benzofuran-2-carboxamide (A256) 1 H NMR (500 MHz, chloroform) δ 7.66 (s, 1H), 7.44 (s, 1H), 7.23 (s, 1H), 7.15 (s, 1H), 6.88 (s, 1H), 6.44 (s, 1H), 6.11 (s, 1H), 4.95 (s, 1H), 4.76 (s, 1H), 4.54 (s, 1H), 3.21 (d, J = 15.0 Hz, 2H), 2.88 (s, 1H), 2.50 (d, J = 13.5 Hz, 2H), 2.19 (s, 2H), 2.26 (s, 2H), 2.27 (s, 2H), 2.28 (s, 2H), 2.29 (s, 2H), 2.36 (s, 2H), 2.29 (s, 2H), 2.34 (s, 2H), 2.28 (s, 2H), 2.29 (s, 2H), 2.36 ... H), 2.01(s, 1H), 1.91(d, J=0.5Hz, 1H), 1.84(s, 2H), 1.76(s, 1H), 1.59(dd, J=42.7, 19.7Hz, 5H), 1.5 3(s, 1H), 1.51(d, J=15.0Hz, 3H), 1.44(dd, J=9.2, 5.8Hz, 5H), 1.37(s, 3H), 1.31(s, 1H), 1.20(s, 2H).

[0332] Example 257. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-6-bromo-benzofuran-2-carboxamide (A257) 1H NMR (500MHz, chloroform)δ 7.54(t, J=2.6Hz, 1H), 7.46(d, J=71.6Hz, 5H), 7.18(s, 3H), 7.11(d, J=2.3Hz, 4H), 6.42(s, 3H), 5.73(s, 3H) ), 5.65(s, 3H), 5.03(s, 2H), 4.95(s, 1H), 4.47(s, 1H), 3.21(d, J=15.0Hz, 6H), 2.99(s, 2H), 2.72(s, 3H), 2 .34(s, 2H), 2.19(s, 5H), 2.01(s, 1H), 1.93(d, J=16.1Hz, 5H), 1.89-1.74(m, 10H), 1.69(d, J=10.0Hz, 8H), 1.62(s, 2H), 1.51(s, 1H), 1.39(d, J=6.9Hz, 1H), 1.38-1.28(m, 4H), 1.20(s, 3H), 1.11(s, 2H), 1.03(s, 3H).

[0333] Example 258. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-1-oxo-3-cyclohexylpropan-2-yl)-5-fluoronicotinamide (A258) 1 H NMR (500 MHz, chloroform) δ 8.58 (s, 1H), 8.40 (s, 1H), 7.77 (s, 1H), 7.29 (d, J = 15.0 Hz, 4H), 7.22 (s, 1H), 7.05 (s, 1H), 6.30 (s, 1H), 5.77 (s, 1H), 4.90 (s, 1H), 4.45 (s, 1H), 4.34 (s, 2H), 3.2 1(d, J=15.0Hz, 2H), 2.97(s, 1H), 2.67(s, 1H), 2.13(s, 1H), 2.01(s, 1H), 1.93( d, J=16.5Hz, 2H), 1.78(m, 2H), 1.75(d, J=7.8Hz, 1H), 1.57(s, 1H), 1.46(m, 9H).

[0334] Example 259. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-ethoxy-benzofuran-2-carboxamide (A259) 1 H NMR (500 MHz, chloroform) δ 7.78-7.52 (m, 1H), 7.29 (d, J = 15.0 Hz, 1H), 7.23 (d, J = 10.0 Hz, 1H), 7.11 (s, 1H), 6.36 (s, 1H), 5.85 (s, 1H), 4.82 (s, 1H), 4.45 (s, 1H), 4.34 (s, 1H), 4.06 (s, 1H), 3.2 1(d, J=15.0Hz, 1H), 2.82(s, 2H), 2.45(d, J=1.0Hz, 1H), 2.01(s, 1H), 1.91(s, 2H) , 1.79-1.57(m, 2H), 1.62-1.57(m, 2H), 1.55-1.41(m, 2H), 1.33(d, J=7.5Hz, 1H).

[0335] Example 260. N-((S)-1-(((S)-4-(3-methylbenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A260) 1 H NMR (500 MHz, chloroform) δ 7.59 (s, 1H), 7.50 (d, J = 5.0 Hz, 2H), 7.28 (s, 1H), 7.21 (d, J = 5.0 Hz, 1H), 7.11 (d, J = 1.5 Hz, 2H), 7.03 (s, 1H), 6.94 (s, 1H), 6.88 (s, 1H), 5.72 (s, 1H), 4.68 (s, 1H), 4. 63(s, 1H), 4.34(s, 2H), 3.21(d, J=15.0Hz, 2H), 2.78(s, 1H), 2.38-2.29(m, 5H), 2 .08-2.03(m, 1H), 2.08-1.89(m, 2H), 1.76(s, 1H), 1.67(s, 1H), 1.55-1.41(m, 8H).

[0336] Example 261. N-((S)-1-(((S)-4-(4-fluorobenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A261) 1 H NMR (500 MHz, chloroform) δ 7.59 (s, 1H), 7.50 (s, 1H), 7.38 (d, J = 2.0 Hz, 2H), 7.28 (s, 1H), 7.22 (s, 1H), 7.16 (s, 1H), 7.07 (s, 1H), 6.86 (s, 1H), 6.12 (s, 1H), 4.80 (s, 1H), 4.53 (s, 1H), 4.34 (s, 1H), 3.21 (d, J =15.0Hz, 2H), 2.91(s, 1H), 2.51(d, J=9.5Hz, 2H), 2.01(s, 1H), 1.91(d, J=4.1Hz, 1H), 1. 76(s, 1H), 1.65(s, 1H), 1.58(s, 1H), 1.51(d, J=15.0Hz, 2H), 1.44(dd, J=8.0, 7.0Hz, 6H).

[0337] Example 262. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-chloro-7-azaindole-2-carboxamide (A262) 1 H NMR (500 MHz, chloroform) δ 8.71 (s, 1H), 8.52 (s, 1H), 8.09 (s, 1H), 7.29 (d, J = 15.0 Hz, 5H), 7.19 (s, 1H), 7.14 (s, 1H), 6.93 (s, 1H), 6.09 (s, 1H), 4.80 (s, 1H), 4.45 (s, 1H), 4.34 (s, 2H), 3.21 (d, J=15.0Hz, 2H), 2.90(s, 1H), 2.44(d, J=5.0Hz, 2H), 2.01(s, 1H), 1.91(d, J=1.4Hz, 1H), 1.76(s, 1H), 1.72(s, 1H), 1.59-1.48(m, 3H), 1.48-1.41(m, 4H), 1.36(s, 1H).

[0338] Example 263. N-((S)-1-(((S)-4-(4-chlorobenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A263) 1 H NMR (500 MHz, chloroform) δ 7.59 (s, 1H), 7.50 (s, 1H), 7.38 (d, J = 9.2 Hz, 5H), 7.28 (s, 1H), 7.22 (s, 1H), 7.16 (s, 1H), 6.86 (s, 1H), 6.12 (s, 1H), 4.80 (s, 1H), 4.53 (s, 1H), 4.34 (s, 2H), 3.21 (d, J = 15.0H z, 2H), 2.92(s, 1H), 2.51(d, J=13.5Hz, 2H), 2.01(s, 1H), 1.91(d, J=3.7Hz, 1H), 1.76( s, 1H), 1.65 (s, 1H), 1.58 (s, 1H), 1.51 (d, J=15.0Hz, 2H), 1.44 (dd, J=8.3, 6.7Hz, 6H).

[0339] Example 264. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-6-bromo-benzofuran-2-carboxamide (A264) 1 H NMR (500 MHz, chloroform) δ 7.50 (d, J = 32.8 Hz, 1H), 7.34-7.26 (m, 3H), 7.18 (s, 1H), 7.11 (s, 1H), 6.87 (s, 1H), 6.12 (s, 1H), 4.78 (s, 1H), 4.54 (s, 1H), 4.34 (s, 1H), 3.21 (d, J = 15.0 Hz, 1H), 2. 90(s, 2H), 2.54(d, J=18.2Hz, 1H), 2.01(s, 1H), 1.92(d, J=6.0Hz, 1H), 1.76(s, 2H) ), 1.65(s, 2H), 1.58(s, 2H), 1.51(d, J=15.0Hz, 1H), 1.44(dd, J=8.2, 6.8Hz, 3H).

[0340] Example 265. N-((S)-1-(((S)-4-(3,4-difluorobenzylamino)-3,4-dione-1-(2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A265) 1 H NMR (500MHz, chloroform) δ 7.53(d, J=44.9Hz, 1H), 7.34(s, 1H), 7.28-7.12(m, 2H), 7.05(s, 1H), 6. 84(s, 1H), 6.11(s, 1H), 4.79(s, 1H), 4.53(s, 1H), 4.33(s, 1H), 3.21(d, J =15.0Hz, 1H), 2.92(s, 1H), 2.50(d, J=17.5Hz, 1H), 2.01(s, 1H), 1.91(d, J=3.9Hz, 2H), 1.76(s, 1H), 1.65(s, 1H), 1.58(s, 1H), 1.55-1.41(m, 4H).

[0341] Example 266. N-((S)-1-(((S)-4-(2-chlorobenzylamino)-3,4-dione-1-(2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A266) 1 H NMR (500 MHz, chloroform) δ 7.66 (s, 1H), 7.44 (s, 1H), 7.23 (s, 1H), 7.15 (s, 1H), 6.88 (s, 1H), 6.44 (s, 1H), 6.11 (s, 1H), 4.95 (s, 1H), 4.76 (s, 1H), 4.54 (s, 1H), 3.21 (d, J = 15.0 Hz, 2H), 2.88 (s, 1H), 2.50 (d, J = 13.5 Hz, 1H), 2.19 (s, 2 H), 2.01(s, 1H), 1.91(d, J=0.5Hz, 1H), 1.84(s, 1H), 1.76(s, 1H), 1.59(dd, J=42.7, 19.7Hz, 5H), 1.5 3(s, 1H), 1.51(d, J=15.0Hz, 3H), 1.44(dd, J=9.2, 5.8Hz, 5H), 1.37(s, 3H), 1.31(s, 1H), 1.20(s, 2H).

[0342] Example 267. N-((S)-1-(((S)-4-(2-methoxybenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A267) 1 H NMR (500MHz, chloroform) δ 7.54(s, 1H), 7.30-7.20(m, 2H), 7.15(s, 1H), 6.95-6.82(m, 2H), 6.11( s, 1H), 4.78(s, 1H), 4.53(s, 1H), 4.23(s, 1H), 3.72(s, 1H), 3.21(d, J=1 5.0Hz, 1H), 2.89(s, 1H), 2.55(d, J=18.5Hz, 1H), 2.01(s, 1H), 1.91(d, J =5.9Hz, 1H), 1.76(s, 1H), 1.65(s, 1H), 1.58(s, 1H), 1.55-1.35(m, 4H).

[0343] Example 268. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-pyridazine-2-carboxamide (A268) 1 H NMR (500MHz, chloroform)δ 9.81(s, 1H), 8.52(s, 1H), 7.99(s, 1H), 7.33-7.26(m, 6H), 6.71(s, 1H), 6.06(s, 1H), 4.75(s, 1H), 4.45(s, 1H), 4.34(s, 2H), 3.21(d, J=15 .0Hz, 2H), 2.83(s, 1H), 2.65(s, 1H), 2.52(s, 1H), 2.01(s, 1H), 1.90(d, J=8.1Hz, 1H), 1.76(s, 1H), 1.65-1.28(m, 9H), 1.39-1.28(m, 1H).

[0344] Example 269. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-4,5 indole-2-carboxamide (A269) 1 H NMR (500 MHz, chloroform) δ 8.49 (s, 1H), 7.33-7.26 (m, 7H), 7.20 (s, 2H), 7.10 (s, 1H), 6.87 (s, 1H), 6.11 (s, 1H), 4.78 (s, 1H), 4.52 (s, 1H), 4.34 (s, 2H), 3.21 (d, J = 15.0 Hz, 2H), 2.92 (s, 1H), 2.54(d, J=17.0Hz, 3H), 2.01(s, 1H), 1.92(d, J=8.4Hz, 2H), 1.76(s, 1H), 1.64(s, 1H), 1.58(s, 1H), 1.51(d, J=15.0Hz, 4H), 1.44(dd, J=9.9, 5.2Hz, 6H).

[0345] Example 270. N-((S)-1-(((S)-4-(3,5-difluorobenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A270) 1 H NMR (500 MHz, chloroform) δ 7.54 (d, J = 45.0 Hz, 1H), 7.35 (s, 1H), 7.27 (s, 1H), 7.21 (s, 1H), 7.15 (s, 2H), 6.85 (d, J = 1.8 Hz, 5H), 6.79 (s, 1H), 6.11 (s, 2H), 4.79 (s, 1H), 4.53 (s, 1H), 4.33 (s, 3H). H), 3.21(d, J=15.0Hz, 4H), 2.91(s, 1H), 2.52(s, 2H), 2.48(s, 2H), 2.01(s, 1H), 1.91(d, J=3.5Hz, 2H), 1.76(s, 2H), 1.65(s, 2H), 1.58(s, 2H), 1.55-1.41(m, 7H).

[0346] Example 271. N-((S)-1-(((S)-4-(4-methoxybenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A271) 1 H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 8.13(t, J=5.7Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.76(d, J=2.0Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H) ), 7.43-7.34(m, 2H), 7.19(dt, J=8.4, 1.0Hz, 2H), 6.87-6.82(m, 2H), 6.26(t, J=4.0Hz, 1H), 4.50(ddt, J=5.8, 3.7, 1.1Hz, 2H), 4.44(dt, J=9.2, 7.4Hz, 1H), 4.26(dt, J=9.9, 6.7Hz, 1H), 3.78(s, 2H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2. 13(ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 631.31[M+H] + .

[0347] Example 272. N-((S)-1-(((S)-4-(4-methylbenzylmethylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A272) 1H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 7.85(d, J=9.7Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H), 7.43-7.34 (m, 2H), 7.14(dt, J=8.0, 1.1Hz, 2H), 7.10(dq, J=7.3, 0.7Hz, 2H), 6.26(t, J=4.0Hz, 1H), 4.55-4.48(m, 2H), 4.50-4.4 3(m, 1H), 4.26(dt, J=9.9, 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.99(s, 2H), 2.61(tdd, J=8.7, 6.8, 4.1Hz, 1H), 2.16(ddd, J =15.0, 8.8, 7.6Hz, 1H), 1.94(ddd, J=15.0, 8.8, 7.6Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 629.33[M+H] + .

[0348] Example 273. N-((S)-1-(((S)-4-(4-nitrobenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A273) 1H NMR (500MHz, chloroform-d)δ 8.21-8.13(m, 3H), 8.10(t, J=5.8Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60(q, J=1.1 Hz, 1H), 7.60-7.52(m, 2H), 7.43-7.34(m, 2H), 6.26(t, J=4.0Hz, 1H), 4.50(ddt, J=5.6, 4.6, 0.9Hz, 2H), 4.44(dt, J=9.2, 7.4Hz, 1H), 4.26(dt, J=9.9, 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J=15.0, 8.8, 7. 3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.71(m, 4H), 1.74-1.59(m, 3H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 646.28[M+H] + .

[0349] Example 274. N-((S)-1-(((S)-4-(2,4,6-trimethylbenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A274) 1H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.80-7.75(m, 2H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H), 7.43-7 .34(m, 2H), 6.78(s, 2H), 6.26(t, J=4.0Hz, 1H), 4.50(dd, J=6.0, 2.9Hz, 2H), 4.44(dt, J=9.2, 7.4Hz, 1H), 4.26 (dt, J=9.9, 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.23(s, 2H), 2.13(ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 643.34[M+H] + .

[0350] Example 275. N-((S)-1-(((S)-4-(4-phenylbenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A275) 1H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 8.13(t, J=5.7Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.62-7.49(m , 5H), 7.48-7.41(m, 2H), 7.43-7.34(m, 3H), 7.30(dt, J=8.4, 1.0Hz, 2H), 6.26(t, J=4.0Hz, 1H), 4.49(ddt, J=5.7, 2.1, 1.0H z, 2H), 4.44 (dt, J=9.2, 7.4Hz, 1H), 4.26 (dt, J=9.9, 6.7Hz, 1H), 3.27-3.14 (m, 2H), 2.61 (tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13 (ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 677.33[M+H] + .

[0351] Example 276. N-((S)-1-(((S)-4-(2,4,6-trimethylbenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A276) 1H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.79-7.72(m, 2H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H), 7.43-7 .34(m, 2H), 7.08(dd, J=8.1, 7.1Hz, 1H), 7.00-6.95(m, 2H), 6.26(t, J=4.0Hz, 1H), 4.53-4.44(m, 2H), 4.46-4.3 9(m, 1H), 4.26(dt, J=9.9, 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J=15.0 , 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 629.33[M+H] + .

[0352] Example 277. N-((S)-1-(((S)-4-(4-cyanobenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A277) 1H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 8.13(t, J=5.7Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.62- 7.56(m, 2H), 7.59-7.52(m, 1H), 7.44-7.34(m, 4H), 6.26(t, J=4.0Hz, 1H), 4.49(ddt, J=5.7, 2.1, 0.9Hz, 2H), 4.44(d t, J=9.2, 7.4Hz, 1H), 4.26(dt, J=9.9, 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J =15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 626.29[M+H] + .

[0353] Example 278. N-((S)-1-(((S)-4-(4-trifluoromethoxybenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A278) 1H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 8.13(t, J=5.7Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.52(m , 1H), 7.43-7.34(m, 2H), 7.23(dt, J=8.3, 1.1Hz, 2H), 7.17-7.11(m, 2H), 6.26(t, J=4.0Hz, 1H), 4.50(ddt, J=5.8, 3.6, 1.0H z, 2H), 4.44 (dt, J=9.2, 7.4Hz, 1H), 4.26 (dt, J=9.9, 6.7Hz, 1H), 3.27-3.14 (m, 2H), 2.61 (tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13 (ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 685.27[M+H] + .

[0354] Example 279. N-((S)-1-(((S)-4-(2 cyanobenzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A279) 1H NMR (500MHz, chloroform-d)δ 8.23-8.16(m, 2H), 7.89(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.64-7.58(m, 1H), 7.61 -7.52(m, 1H), 7.43-7.32(m, 5H), 6.26(t, J=4.0Hz, 1H), 4.56(dd, J=5.7, 1.0Hz, 2H), 4.44(dt, J=9.2, 7.4Hz, 1H), 4.26(dt, J=9.9, 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J=15.0, 8 .8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 626.30[M+H] + .

[0355] Example 280. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-7 azaindole-2-carboxamide (A280) 1H NMR (500MHz, chloroform-d)δ 8.69(dd, J=3.8, 1.8Hz, 1H), 8.48(d, J=8.2Hz, 1H), 8.28(dt, J=7.3, 1.9Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.89(d, J=9.3 Hz, 1H), 7.54(d, J=2.2Hz, 1H), 7.40-7.32(m, 1H), 7.34-7.30(m, 1H), 7.32-7.27(m, 2H), 7.30-7.22(m, 2H), 6.26(t, J= 4.0Hz, 1H), 4.48(t, J=1.0Hz, 1H), 4.49-4.39(m, 3H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 601.31[M+H] + .

[0356] Example 281. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-chloro-benzofuran-2-carboxamide (A281) 1H NMR (500MHz, chloroform-d)δ 8.19-8.08(m, 2H), 7.89(d, J=9.3Hz, 1H), 7.83(t, J=2.1Hz, 1H), 7.75(d, J=2.1Hz, 1H), 7.69(d, J=8.4Hz, 1H ), 7.48(dd, J=8.4, 2.0Hz, 1H), 7.35-7.22(m, 5H), 6.26(t, J=4.0Hz, 1H), 4.50-4.39(m, 3H), 4.26(dt, J=9.9 , 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99 (ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.74(m, 3H), 1.77-1.59(m, 4H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 635.26[M+H] + .

[0357] Example 282. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-methoxy-benzofuran-2-carboxamide (A282) 1H NMR (500MHz, chloroform-d)δ 8.16(d, J=9.9Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.67(d, J=2.1Hz, 1H), 7.51(d, J=8.4Hz, 1H), 7.35-7.22(m , 5H), 7.16(t, J=2.0Hz, 1H), 7.08(dd, J=8.4, 1.8Hz, 1H), 6.26(t, J=4.0Hz, 1H), 4.47(dt, J=5.7, 1.0Hz, 2H), 4.44(dt, J=9.2, 7 .4Hz, 1H), 4.26(dt, J=9.9, 6.7Hz, 1H), 3.82(s, 2H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J=15.0, 8 .8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.71(m, 4H), 1.75-1.59(m, 3H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 631.31[M+H] + .

[0358] Example 283. N-((R)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A283) 1H NMR (500MHz, chloroform-d)δ 8.19(d, J=9.9Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H), 7.43-7.35(m, 2H), 7.35-7.22(m, 5H), 6.26(t, J=4.0Hz, 1H), 4.50-4.39(m, 3H), 4 .26(dt, J=9.9, 6.7Hz, 1H), 3.27-3.14(m, 2H), 2.61(tdd, J=8.9, 6.9, 4.2Hz, 1H), 2.13(ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.86-1.59(m, 7H), 1.57-1.34(m, 8H), 1.32-1.20(m, 2H). ESI-MS m / z 601.29[M+H] + .

[0359] Example 284. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A284) 1H NMR (500MHz, chloroform-d)δ 8.37(d, J=9.7Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.83(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H), 7.43-7.35(m, 2H), 7.35-7.22(m, 6H), 7.01(td, J=7.8, 1.9Hz, 2H), 6.96(dtt, J=7.9, 1.9, 1.0Hz, 1H), 6.26(t, J=4.0Hz, 1 H), 4.78(dt, J=9.7, 6.2Hz, 1H), 4.54-4.46(m, 1H), 4.48(s, 1H), 4.47(t, J=0.9Hz, 1H), 3.27-3.14(m, 2H), 3.05-2.93(m, 2H), 2.61 (tdd, J=8.9, 6.9, 4.3Hz, 1H), 2.13 (ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99 (ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.81-1.61 (m, 4H). ESI-MS m / z 613.24[M+H] + .

[0360] Example 285. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-phenyl-1-oxopropan-2-yl)-5-fluoro-indole-2-carboxamide (A285) 1H NMR (500MHz, chloroform-d)δ 9.91(s, 1H), 8.35(d, J=8.1Hz, 1H), 7.83(d, J=9.3Hz, 1H), 7.63(dt, J=8.0, 2.5Hz, 1H), 7.50(dd, J=7.2, 5.0Hz, 1H), 7.30-7.14(m, 7H), 7.08(ddd, J=8.1, 7.1, 2.7Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.78(dt, J=8.1, 6.2Hz, 1H), 4.44(dt, J =9.3, 7.3Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 3.08-3.01(m, 1H), 3.04-2.97(m, 1H), 2.68(tdd, J=7.7, 5.7 , 3.9Hz, 1H), 2.17-2.08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.82(dtd, J=12.2, 3.7, 2.3Hz, 1H). ESI-MS m / z 564.25[M+H] + .

[0361] Example 286. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-methoxy-indole-2-carboxamide (A286) 1H NMR (500MHz, chloroform-d)δ 9.91(s, 1H), 8.32(d, J=8.2Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.48(d, J=8.2Hz, 1H), 7.37-7.3 1(m, 2H), 6.82(dd, J=7.3, 2.4Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.49-4.36(m, 2H), 3.83(s, 2H) , 3.67(dp, J=8.2, 4.9Hz, 1H), 3.33-3.22(m, 2H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.13(d t, J=15.2, 7.5Hz, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.33(m, 21H), 1.31-1.20(m, 2H). ESI-MS m / z 608.34[M+H] + .

[0362] Example 287. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-phenyl-1-oxopropan-2-yl)-1-methyl-indole-2-carboxamide (A287) 1H NMR (500MHz, chloroform-d)δ 8.18(d, J=7.7Hz, 1H), 7.85-7.75(m, 2H), 7.48(d, J=8.2Hz, 1H), 7.43(dd, J=8.3, 1.2Hz, 1H), 7.31-7.15(m, 8H), 6.13(t, J=3.1H) z, 1H), 4.75(dt, J=7.5, 6.2Hz, 1H), 4.41(dt, J=9.2, 7.4Hz, 1H), 3.93(s, 2H), 3.67(dp, J=8.2, 4.9Hz, 1H), 3.33-3.26(m, 1H), 3.2 9-3.22(m, 1H), 3.02(ddt, J=6.2, 3.2, 1.0Hz, 2H), 2.67(tdd, J=7.8, 5.7, 3.9Hz, 1H), 2.13(dt, J=15.3, 7.5Hz, 1H), 2.02(dt, J=1 5.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.82(dtd, J=12.2, 3.7, 2.3Hz, 1H), 1.75-1.40(m, 8H), 1.43-1.36(m, 2H), 1.40-1.33(m, 1H). ESI-MS m / z 586.29[M+H] + .

[0363] Example 288. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-phenyl-1-oxopropan-2-yl)-5-fluoro-indole-2-carboxamide (A288) 1H NMR (500MHz, chloroform-d)δ 9.91(s, 1H), 8.35(d, J=8.0Hz, 1H), 7.83(d, J=9.3Hz, 1H), 7.63(dt, J=7.9, 2.5Hz, 1H), 7.53-7.46(m, 2H), 7.30-7.14(m, 5H), 7. 08(ddd, J=8.1, 7.1, 2.7Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.78(dt, J=8.1, 6.2Hz, 1H), 4.41(dt, J=9.2, 7.4Hz, 1H), 3.67(dp, J=8.2 , 4.9Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 3.02(ddt, J=6.2, 3.2, 1.0Hz, 2H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.13(d t, J=15.2, 7.5Hz, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.82(dtd, J=12.2, 3.7, 2.3Hz, 1H), 1.75-1.33(m, 11H). ESI-MS m / z 590.27[M+H] + .

[0364] Example 289. N-((R)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A289) 1H NMR (500MHz, chloroform-d)δ 8.37(d, J=9.7Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.83(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.5 2(m, 1H), 7.43-7.35(m, 2H), 7.38-7.22(m, 8H), 7.07-7.00(m, 2H), 6.26(t, J=4.0Hz, 1H), 4.75(dt, J=9.7, 6.2Hz, 1H), 4 .54-4.46(m, 1H), 4.50-4.45(m, 1H), 4.47(t, J=0.9Hz, 1H), 3.27-3.14(m, 2H), 3.08(ddt, J=6.2, 2.9, 1.1Hz, 2H), 2.61( tdd, J=8.9, 6.9, 4.3Hz, 1H), 2.13(ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.81-1.61(m, 4H). ESI-MS m / z 613.24[M+H] + .

[0365] Example 290. N-((R)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A290) 1H NMR (500MHz, chloroform-d)δ 8.37(d, J=9.7Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.83(d, J=9.3Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.5 2(m, 1H), 7.43-7.35(m, 2H), 7.35-7.22(m, 5H), 7.10-7.03(m, 1H), 7.03-6.96(m, 2H), 6.26(t, J=4.0Hz, 1H), 4.78(dt, J= 9.7, 6.2Hz, 1H), 4.54-4.46(m, 1H), 4.50-4.45(m, 1H), 4.47(t, J=0.9Hz, 1H), 3.27-3.14(m, 2H), 3.07-2.95(m, 2H), 2.61 (tdd, J=8.9, 6.9, 4.3Hz, 1H), 2.13 (ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99 (ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.81-1.61 (m, 4H). ESI-MS m / z 631.23[M+H] + .

[0366] Example 291. N-((S)-1-(((S)-4-(t-butylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-phenyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A291) 1H NMR (500MHz, chloroform-d)δ 8.37(d, J=9.7Hz, 1H), 7.83(d, J=9.2Hz, 1H), 7.76(d, J=2.2Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H) , 7.43-7.34(m, 2H), 7.30-7.16(m, 6H), 6.13(t, J=3.1Hz, 1H), 4.70(dt, J=9.7, 6.2Hz, 1H), 4.44(dt, J=9. 3, 7.3Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 3.08-2.97(m, 2H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H) , 2.17-2.08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.82(dtd, J=12.2, 3.7, 2.3Hz, 1H). ESI-MS m / z 547.25[M+H] + .

[0367] Example 292. N-((S)-1-(((S)-4-(cyclohexylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,3-dihydrobenzo[b]1,4-dioxine-6-carboxamide (A292) 1H NMR (500MHz, chloroform-d)δ 7.95-7.87(m, 2H), 7.54-7.46(m, 2H), 7.40(d, J=2.1Hz, 1H), 6.89(d, J=8.5Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.40(dt, J=9.3, 7.3Hz, 1H), 4. 36-4.29(m, 1H), 4.29(dd, J=4.8, 2.4Hz, 2H), 4.27(ddd, J=4.7, 3.0, 2.2Hz, 2H), 3.67(dp, J=8.2, 4.9Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22 (m, 1H), 2.67(tdd, J=7.8, 5.7, 3.9Hz, 1H), 2.13(dt, J=15.2, 7.5Hz, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.77(m, 2) H), 1.80-1.66(m, 4H), 1.68-1.61(m, 1H), 1.64-1.58(m, 1H), 1.61-1.49(m, 2H), 1.53-1.38(m, 10H), 1.41-1.33(m, 2H), 1.31-1.20(m, 2H). ESI-MS m / z 597.33[M+H] + .

[0368] Example 293. N-((S)-1-(((S)-4-((R)-1-phenyl-ethyl)-amino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A293) 1H NMR (500MHz, chloroform-d)δ 8.39-8.32(m, 2H), 8.20(d, J=8.3Hz, 1H), 8.07-8.01(m, 1H), 7.97-7.91(m, 1H), 7.89(d, J=9.3Hz, 1H), 7.73(td, J=7.9, 1.1Hz, 1H), 7.53(td, J=7.8, 1.2Hz, 1H), 7.36-7.29(m, 2H), 7.32-7.22(m, 4H), 6.13(t, J=3.1Hz, 1H), 5.01(dtdd, J=8.4, 6.1, 5.1, 1.1Hz, 1H), 4.48-4.37(m, 2H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.17- 2.08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.68(m, 4H), 1.57-1.34(m, 12H), 1.31-1.20(m, 2H). ESI-MS m / z 612.31[M+H] + .

[0369] Example 294. N-((S)-1-(((S)-4-morpholinyl-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A294) 1H NMR (500MHz, chloroform-d) δ 8.39-8.32(m, 2H), 8.20(d, J=8.3Hz, 1H), 8.07-8.01(m, 1H), 7.94(dt, J=8. 0, 0.8Hz, 1H), 7.84(d, J=9.7Hz, 1H), 7.73(td, J=7.9, 1.1Hz, 1H), 7.53(td, J =7.9, 1.2Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.52(dt, J=9.7, 7.7Hz, 1H), 4.41( dt, J=9.3, 6.6Hz, 1H), 3.71(ddd, J=9.7, 6.3, 3.6Hz, 4H), 3.63(dd, J=6.4, 3. 6Hz, 2H), 3.55(dd, J=6.4, 3.6Hz, 2H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H) , 2.64(tdd, J=7.8, 5.7, 3.9Hz, 1H), 2.16(dt, J=15.3, 7.6Hz, 1H), 2.01(dt, J =15.1, 7.7Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.80(m, 1H), 1.82-1.77(m, 1H), 1.80-1.75(m, 1H), 1.77-1.68(m, 1H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 578.29[M+H] + .

[0370] Example 295. N-((S)-1-(((S)-4-((S)-1-phenyl-ethyl)-amino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A295) 1H NMR (500MHz, chloroform-d)δ 8.39-8.32(m, 2H), 8.20(d, J=8.3Hz, 1H), 8.07-8.01(m, 1H), 7.97-7.91(m, 1H), 7.89(d, J=9.3Hz, 1H), 7.73(td, J=7.9 , 1.1Hz, 1H), 7.53(td, J=7.8, 1.2Hz, 1H), 7.36-7.29(m, 2H), 7.32-7.22(m, 4H), 6.13(t, J=3.1Hz, 1H), 5.03(dqt, J=8. 1, 6.1, 1.1Hz, 1H), 4.48-4.37(m, 2H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.17-2 .08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.68(m, 4H), 1.57-1.34(m, 12H), 1.31-1.20(m, 2H). ESI-MS m / z 612.31[M+H] + .

[0371] Example 296. N-((S)-1-(((S)-4-diethylamino-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A296) 1H NMR (500MHz, chloroform-d)δ 8.39-8.32(m, 2H), 8.20(d, J=8.3Hz, 1H), 8.07-8.01(m, 1H), 7.97-7.91(m, 1H), 7.85(d, J=9.7Hz, 1H), 7.73(td, J=7.9, 1.1 Hz, 1H), 7.53(td, J=7.8, 1.2Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.52(dt, J=9.7, 7.7Hz, 1H), 4.41(dt, J=9.3, 6.6Hz, 1H), 3.45(q , J=7.3Hz, 4H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.67(tdd, J=7.9, 5.7, 3.9Hz, 1H), 2.17(dt, J=15.3, 7.7Hz, 1H), 2.01 (dt, J=15.1, 7.6Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.70(m, 4H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H), 1.20(t, J=7.3Hz, 6H). ESI-MS m / z 564.31[M+H] + .

[0372] Example 297. N-((S)-1-(((S)-4-(4-fluorobenzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-quinoline-2-carboxamide (A297) 1H NMR (500MHz, chloroform-d)δ 8.39-8.32(m, 2H), 8.20(d, J=8.2Hz, 1H), 8.13(t, J=5.7Hz, 1H), 8.07-8.01(m, 1H), 7.97-7.91(m, 1H), 7.89(d, J=9.3Hz, 1H), 7.73(td, J=7) .9, 1.1Hz, 1H), 7.53(td, J=7.7, 1.1Hz, 1H), 7.32(ddt, J=7.5, 5.0, 1.0Hz, 2H), 7.11-7.03(m, 2H), 6.13(t, J=3.1Hz, 1H), 4.55-4.45(m, 3H) , 4.41(dt, J=9.3, 6.6Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.67(tdd, J=7.8, 5.7, 3.9Hz, 1H), 2.13(dt, J=15.2, 7.5Hz, 1H), 2.02( dt. ESI-MS m / z 616.28[M+H] + .

[0373] Example 298. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-bromoimidazo[1,2-a]pyridine-2-carboxamide (A298) 1H NMR (500MHz, chloroform-d)δ 8.39-8.32(m, 2H), 8.20(d, J=8.2Hz, 1H), 8.13(t, J=5.7Hz, 1H), 8.07-8.01(m, 1H), 7.94(dt, J=8.0, 0.8Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.73(td, J=7.9, 1.1Hz, 1H), 7.53(td, J=7.9, 1.2Hz, 1H), 7.19(dt, J=8.4, 1.0Hz, 2H), 6.87-6.82(m, 2H), 6.13(t, J=3.1Hz, 1H), 4.55-4 .49(m, 1H), 4.52-4.44(m, 2H), 4.41(dt, J=9.3, 6.6Hz, 1H), 3.78(s, 2H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.67(tdd, J=7.8, 5.7, 3 .9Hz, 1H), 2.13(dt, J=15.2, 7.5Hz, 1H), 2.07-1.99(m, 1H), 1.94-1.86(m, 1H), 1.86-1.68(m, 4H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 628.31[M+H] + .

[0374] Example 299. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-bromoimidazo[1,2-a]pyridine-2-carboxamide (A299) 1H NMR (500MHz, chloroform-d)δ 9.03(d, J=6.6Hz, 1H), 8.11(t, J=5.8Hz, 1H), 8.01(t, J=1.6Hz, 1H), 7.92(dd, J=23.3, 8.9Hz, 2H), 7.79(dd, J=7.4, 1.6Hz , 1H), 7.44(s, 0H), 7.35-7.17(m, 6H), 6.69(dd, J=3.3, 2.0Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.54-4.46(m, 1H), 4.47(dd, J=5 .8, 0.9Hz, 2H), 4.33(dt, J=8.4, 6.7Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.1 7-2.08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.69(m, 4H), 1.57-1.34(m, 9H), 1.31-1.20(m, 2H). ESI-MS m / z 586.30[M+H] + .

[0375] Example 300. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-bromoimidazo[1,2-a]pyridine-2-carboxamide (A300) 1H NMR (500MHz, chloroform-d)δ 8.74-8.70(m, 1H), 8.58(d, J=9.3Hz, 1H), 8.47(s, 1H), 8.11(t, J=5.8Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.52(dd, J=8.8, 1.3 Hz, 1H), 7.42(d, J=8.8Hz, 1H), 7.35-7.22(m, 5H), 6.13(t, J=3.1Hz, 1H), 4.54-4.46(m, 1H), 4.48(d, J=0.9Hz, 1H), 4.47(t , J=0.9Hz, 1H), 4.41(dt, J=9.3, 6.6Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.1 7-2.08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.68(m, 4H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 665.20[M+H] + .

[0376] Example 301. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-7-bromo-quinoline-2-carboxamide (A301) 1H NMR (500MHz, chloroform-d)δ 8.36-8.30(m, 2H), 8.19(d, J=2.1Hz, 1H), 8.15(d, J=8.2Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.94-7.86(m, 2H), 7.62(dd, J=8 .5, 2.3Hz, 1H), 7.35-7.22(m, 5H), 6.13(t, J=3.1Hz, 1H), 4.54-4.45(m, 3H), 4.41(dt, J=9.3, 6.6Hz, 1H), 3.33-3.26(m, 1 H), 3.29-3.22(m, 1H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.17-2.08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m , 1H), 1.86-1.80(m, 1H), 1.82-1.77(m, 1H), 1.80-1.75(m, 1H), 1.77-1.68(m, 1H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 676.20[M+H] + .

[0377] Example 302. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-2,3-dihydrobenzo[b]1,4-dioxine-6-carboxamide (A302) 1H NMR (500MHz, chloroform-d)δ 8.11(t, J=5.8Hz, 1H), 7.95-7.87(m, 2H), 7.52(dd, J=8.4, 2.2Hz, 1H), 7.40(d, J=2.1Hz, 1H), 7.35-7.22(m, 5H), 6.89(d, J=8. 5Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.54-4.46(m, 1H), 4.48(d, J=0.9Hz, 1H), 4.47(t, J=0.9Hz, 1H), 4.36-4.29(m, 1H), 4.29(dd, J=4.8, 2.4Hz, 2H), 4.27(ddd, J=4.7, 3.0, 2.2Hz, 2H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H) , 2.17-2.08(m, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1.86-1.69(m, 4H), 1.57-1.34(m, 9H), 1.31-1.20(m, 2H). ESI-MS m / z 605.29[M+H] + .

[0378] Example 303. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-methyl-isoxazole-2-carboxamide (A303) 1H NMR (500MHz, chloroform-d)δ 8.36(d, J=9.3Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.89(d, J=9.3Hz, 1H), 7.35-7.22(m, 5H), 6.50(s, 1H), 6.13(t, J=3 .1Hz, 1H), 4.47(dt, J=5.4, 0.9Hz, 2H), 4.48-4.37(m, 2H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 2.67(tdd, J=7. 8, 5.7, 3.9Hz, 1H), 2.52(s, 2H), 2.13(dt, J=15.2, 7.5Hz, 1H), 2.02(dt, J=15.0, 7.5Hz, 1H), 1.94-1.86(m, 1H), 1 .86-1.80(m, 1H), 1.82-1.77(m, 1H), 1.80-1.75(m, 1H), 1.77-1.68(m, 1H), 1.57-1.34(m, 8H), 1.31-1.20(m, 2H). ESI-MS m / z 552.27[M+H] + .

[0379] Example 304. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(2fluorophenyl)-1-oxopropan-2-yl)-quinoline-2-carboxamide (A304) 1H NMR (500MHz, chloroform-d) δ 8.43-8.32(m, 2H), 8.20(d, J=8.2Hz, 1H), 8.11(t, J=5.8Hz, 1H), 8.04(dd , J=8.1, 1.2Hz, 1H), 7.97-7.91(m, 1H), 7.83(d, J=9.1Hz, 1H), 7.73(td, J= 7.9, 1.1Hz, 1H), 7.53(td, J=7.7, 1.2Hz, 1H), 7.36-7.15(m, 7H), 7.10(td, J=7.9, 1.2Hz, 1H), 6.13(t, J=3.1Hz, 1H), 4.80(dt, J=9.2, 7.3Hz, 1H), 4.5 4-4.46(m, 1H), 4.47(dd, J=5.8, 0.9Hz, 2H), 3.33-3.22(m, 2H), 3.21(ddd, J=15.8, 7.4, 0.9Hz, 1H), 3.09(ddd, J=15.9, 7.3, 0.7Hz, 1H), 2.68(tdd, J= 7.7, 5.7, 3.9Hz, 1H), 2.13(dt, J=15.2, 7.5Hz, 1H), 2.07-1.99(m, 1H), 1.9 0(dddd, J=12.1, 6.1, 3.8, 2.5Hz, 1H), 1.82(dtd, J=12.2, 3.7, 2.3Hz, 1H). ESI-MS m / z 610.24[M+H] + .

[0380] Example 305. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3-fluorophenyl)-1-oxopropan-2-yl)-quinoline-2-carboxamide (A305) 1H NMR (500MHz, chloroform-d) δ 8.43(d, J=9.1Hz, 1H), 8.35(d, J=8.3Hz, 1H), 8.20(d, J=8.2Hz, 1H), 8.11( t, J=5.8Hz, 1H), 8.04(dd, J=8.1, 1.2Hz, 1H), 7.97-7.91(m, 1H), 7.83(d, J= 9.3Hz, 1H), 7.73(td, J=7.9, 1.1Hz, 1H), 7.53(td, J=7.7, 1.2Hz, 1H), 7.35- 7.22(m, 6H), 7.01(td, J=7.8, 1.9Hz, 2H), 6.96(dtt, J=7.9, 1.9, 1.0Hz, 1H) , 6.13(t, J=3.1Hz, 1H), 4.80(dt, J=9.3, 6.3Hz, 1H), 4.54-4.46(m, 1H), 4. 47(dd, J=5.8, 0.9Hz, 2H), 3.33-3.22(m, 2H), 3.05-2.93(m, 2H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.13(dt, J=15.2, 7.5Hz, 1H), 2.07-1.99(m, 1H), 1. 90 (dddd, J=12.1, 6.1, 3.8, 2.4Hz, 1H), 1.82 (dtd, J=12.3, 3.7, 2.3Hz, 1H). ESI-MS m / z 610.23[M+H] + .

[0381] Example 306. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-quinoline-2-carboxamide (A306) 1H NMR (500MHz, chloroform-d)δ 8.43(d, J=9.1Hz, 1H), 8.35(d, J=8.2Hz, 1H), 8.20(d, J=8.3Hz, 1H), 8.11(t, J=5.8Hz, 1H), 8.07-8.01(m, 1H), 7.97-7.91(m, 1H), 7.83(d, J= 9.3Hz, 1H), 7.73(td, J=7.9, 1.1Hz, 1H), 7.53(td, J=7.8, 1.2Hz, 1H), 7.35-7.22(m, 7H), 7.07-7.00(m, 2H), 6.13(t, J=3.1Hz, 1H), 4.77(dt, J=9.2, 6.2Hz, 1H), 4.54-4.46(m, 1H), 4.48(d, J=0.9Hz, 1H), 4.47(t, J=0.9Hz, 1H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 3.13-3.01(m, 2H) , 2.67(tdd, J=7.8, 5.7, 3.9Hz, 1H), 2.13(dt, J=15.2, 7.5Hz, 1H), 2.07-1.99(m, 1H), 1.94-1.86(m, 1H), 1.82(dtd, J=12.2, 3.7, 2.2Hz, 1H). ESI-MS m / z 610.24[M+H] + .

[0382] Example 307. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-quinoline-2-carboxamide (A307) 1H NMR (500MHz, chloroform-d)δ 8.43(d, J=9.1Hz, 1H), 8.35(d, J=8.2Hz, 1H), 8.20(d, J=8.3Hz, 1H), 8.11(t, J=5.8Hz, 1H), 8.07-8.01(m, 1H), 7.97-7.91(m, 1H), 7.83(d, J=9 .3Hz, 1H), 7.73(td, J=7.9, 1.1Hz, 1H), 7.53(td, J=7.8, 1.2Hz, 1H), 7.35-7.22(m, 5H), 7.10-7.03(m, 1H), 7.03-6.96(m, 2H), 6.13(t, J=3.1Hz) , 1H), 4.80(dt, J=9.3, 6.3Hz, 1H), 4.54-4.46(m, 1H), 4.47(dd, J=5.7, 0.9Hz, 2H), 3.33-3.26(m, 1H), 3.29-3.22(m, 1H), 3.00(ddt, J=6.2, 2. 8, 1.0Hz, 2H), 2.68(tdd, J=7.7, 5.7, 3.9Hz, 1H), 2.17-2.08(m, 1H), 2.07-1.99(m, 1H), 1.94-1.86(m, 1H), 1.82(dtd, J=12.2, 3.7, 2.2Hz, 1H). ESI-MS m / z 628.23[M+H] + .

[0383] Example 308. N-((S)-1-(((S)-4-(benzylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(2-fluorophenyl)-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A308) 1H NMR (500MHz, chloroform-d)δ 8.33(d, J=9.7Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.83(d, J=9.1Hz, 1H), 7.76(d, J=1.9Hz, 1H), 7.75-7.68(m, 1H), 7.60-7.52(m, 1H), 7.43- 7.34(m, 2H), 7.37-7.26(m, 5H), 7.29-7.23(m, 1H), 7.26-7.18(m, 1H), 7.21-7.17(m, 1H), 7.10(td, J=7.9, 1.2Hz, 1H), 6.26(t, J=4.0Hz) , 1H), 4.77(dt, J=9.7, 7.3Hz, 1H), 4.54-4.46(m, 1H), 4.48(s, 1H), 4.47(t, J=0.9Hz, 1H), 3.27-3.14(m, 3H), 3.09(ddd, J=15.9, 7.3, 0. 8Hz, 1H), 2.61(tdd, J=8.9, 6.9, 4.3Hz, 1H), 2.13(ddd, J=15.0, 8.8, 7.3Hz, 1H), 1.99(ddd, J=15.2, 8.8, 7.3Hz, 1H), 1.81-1.61(m, 4H). ESI-MS m / z 613.23[M+H] + .

[0384] Example 309. N-((S)-1-(((S)-4-(cyclopropylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A309) 1H NMR (500MHz, DMSO-d6)δ 8.71(d, J=5.1Hz, 1H), 8.57(t, J=8.4Hz, 2H), 7.81-7.75(m, 1H), 7.68(dd, J=8.4, 1.0Hz, 1H), 7.63(d, J=1.0Hz, 1H), 7.47(m, 2H), 7.37-7.30(m, 1H), 5.08(m, 1H), 4.59(m, 1H), 3. 10(m, 2H), 2.72(m, 1H), 2.28(m, 1H), 2.11(m, 1H), 1.90(m, 1H), 1.77-1.49(m, 6H), 1.45- 1.34(m, 2H), 1.29-1.06(m, 3H), 0.97-0.87(m, 2H), 0.74-0.59(m, 2H), 0.59-0.26(m, 2H). ESI-MS m / z 551.27[M+H] + .

[0385] Example 310. N-((S)-1-(((S)-4-(cyclopropylamino)-3,4-dione-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-benzofuran-2-carboxamide (A310) 1 H NMR (500MHz, DMSO-d6)δ 8.78-8.63(m, 3H), 7.76(d, J=7.8Hz, 1H), 7.65(d, J=8.4Hz, 1H), 7.55(s, 1H), 7.49-7.43( m, 2H), 7.41-7.35(m, 2H), 7.32(t, J=7.8Hz, 1H), 7.07(t, J=8.4Hz, 2H), 5.13(m, 1H), 4.78( m, 1H), 3.16-3.06(m, 3H), 3.06-2.97(m, 1H), 2.73(m, 1H), 2.27(m, 1H), 2.14(m, 1H), 2.08- 1.89(m, 1H), 1.73(m, 2H), 1.56(m, 1H), 1.42(m, 1H), 0.71-0.60(m, 2H), 0.60-0.42(m, 2H). ESI-MS m / z 563.22[M+H] + .

[0386] Activity test example 1: Evaluation of 2019 novel coronavirus 3CL protease inhibitory activity 2019 novel coronavirus 3CL protease (2019-nCoV 3CL pro Measurement of the inhibitory activity of compounds against 3C protease: Fluorescence resonance energy transfer (FRET) technology is used to measure the inhibitory activity of the enzyme level of inhibitors against 3C protease. In a 96-well plate, add 27.5 μl of buffer (20 mM Tris, 100 mM NaCl, 1 mM EDTA, pH 7.4) to each well, and add 2.5 μl of compound (final concentration is 2 μM, 4 μM, 6 μM, 8 μM, 10 μM, 12 μM, 14 μM, 16 μM, 18 μM, 20 μM, respectively) and 5 μl of EV713Cpro (final concentration is 3 μM). Incubate at 37°C for 15 minutes. Then add 15 μl of fluorescent substrate (final concentration is 20 μM) diluted with buffer. Fluorescence parameters are measured using a Gen5 fluorescence spectrometer, excitation wavelength and emission wavelength are 340nM and 490nM, respectively, maintained at 37℃, and data is read after 10 minutes. A negative control is used, where no compound is added to the control, and the rest is the same. The obtained data is processed with the software GraphPad Prism 5, and the experimental results are as shown in Table 1.

[0387] [Table 2]

[0388] The experimental results showed that most of the compounds had good inhibitory activity against 2019-nCoV 3CL protease, where the inhibitory activity IC of compounds A13 (DC403113) and A42 (DC404001) against 2019-nCoV 3CL protease 50 reaches 2.4 μM and 3.0 μM.

[0389] Activity Test Example 2: Evaluation of human cathepsin L inhibitory activity Measurement of compound inhibitory activity against human cathepsin L (CatL): Fluorescence resonance energy transfer (FRET) technology is used to measure the enzyme-level inhibitory activity against cathepsin L. In a 96-well plate, 10 μl of buffer (50 mM CH3COONa, pH 5.5, 1 mM DTT, 2 mM EDTA) is added to each well, and at the same time, 0.2 μl of compound (final concentrations are 100 nM, 10 nM, 1 nM, 0.1 nM and 0.01 nM, respectively) and 10 μl of cathepsin L are added. Incubate at 25°C for 15 minutes. Then add 10 μl of fluorescent substrate (Z-Phe-Arg-AMC, final concentration is 20 μM) diluted with buffer. Fluorescence parameters are measured using Tecan Infinite 200pro fluorescence spectrometer, excitation wavelength and emission wavelength are 360nM and 465nM, respectively, maintained at 25℃, and data is read after 30 minutes. A negative control is used, where the control does not add compound, and the rest is the same. The obtained data is processed with software GraphPad Prism 8.0, and the experimental results are as shown in Table 2.

[0390] [Table 3]

[0391] The experimental results showed that the test compound had excellent inhibitory activity against human cathepsin L and IC 50 reaches nanomolar levels below 1 nM (e.g., compounds A5, A284, A289, A290, A309, A310).

[0392] Activity Test Example 3: Evaluation of compound 2019 novel coronavirus replication inhibitory activity Measurement of the inhibitory activity of compounds against the replication of each 2019 novel coronavirus (2019-nCov): Add 100 μl / well of gradient concentration of compounds to 96 wells, then add 50 μl / well of virus buffer, and immediately add 50 μl / well of cultured rhabdomyosarcoma cells, and culture at 37°C for 3-4 days until the maximum cytopathic effect is observed. Aspirate the medium, add 75 μl of 5% MTS phenol red medium, and culture at 37°C and 5% CO2 for 1.5 hours. Measure the fluorescence value of each well at 498 nM wavelength, create a curve diagram of compound concentration and cell response, and use the software customized by Accelrys to calculate the EC value of the compound for virus inhibition. 50 Calculate.

[0393] The test results are shown in Figures 1 and 2.

[0394] The results show that the ketoamide compounds of the present invention can effectively inhibit the replication of the 2019 novel coronavirus (Figure 1), and have certain inhibition against different isolated viral strains.

[0395] At present, the positive compound against 2019-nCoV is CQ, which inhibits 2019-nCoV viral replication with its inhibition rate EC 50 =1.13μM. The results show that, using CQ as a positive control, the patented compounds were tested under various concentration gradients, and compounds A13 (3113, DC403113), A42 (4001, DC404001), and A289 (6009, DC406009) all have excellent inhibitory virus activity. Here, the EC 50 The EC50 of 6009 and 4001 was 9237 nM, and the EC50 of 6009 and 4001 was 296.5 nM and 580.5 nM, respectively, indicating that 6009 and 4001 had superior inhibition rates against 2019-nCoV at the virus level to the positive control CQ, indicating superior anti-2019-nCoV potential (Figure 2).

[0396] Activity Test Example 4: DC406009: Toxicity test of repeated intravenous injections for 14 days in SD rats The purpose of this study is to observe the potential toxicity to the body after intravenous injection of DC406009 in SD rats for 7 consecutive days and to determine the possible toxicity target period. To provide non-toxic and / or toxic response doses to serve as a reference for subsequent toxicity study design and clinical trial design. To evaluate the exposure level of the drug in vivo, an accompanying toxicokinetic evaluation will be performed.

[0397] Thirty-six SD rats were divided into eight groups (toxicity test groups, 5 groups in total, 3 males and 3 females in each group, and toxicological satellite groups, 3 groups in total, 1 male and 1 female), and were intravenously injected with the solvent (5% DMSO / 5% EtOH / 40% PEG300 / 50% NaCl), 0.9% sodium chloride injection, and DC406009 (5, 15, 30 mg / kg / day) once a day for seven consecutive days, and all animals were euthanized and dissected on the eighth day. During the test period, the following indicators were evaluated: toxicity (sample collection only), clinical observation, body weight, food intake, clinical pathology (hematology, blood coagulation, plasma biochemistry), and anatomical macroscopic morphological observation. The results show that under the test conditions, SD rats were intravenously injected with DC406009 (5, 15, 30 mg / kg / day) once a day for 7 consecutive days, and all animals were able to tolerate it, with the maximum tolerated dose (MTD) exceeding 30 mg / kg / day, indicating that compound DC406009 has a good safety profile.

[0398] All documents mentioned in the present invention are incorporated by reference in this application as if each document was incorporated by reference individually. Furthermore, after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalents are also included in the scope defined by the appended claims of this application.

Claims

1. A pharmaceutical composition for use as a 3CL protease inhibitor and a human cathepsin L inhibitor, and for treating and / or preventing and alleviating associated diseases caused by 2019 novel coronavirus (2019-nCov) infection, comprising: The pharmaceutical composition comprises: (a) a ketoamide compound represented by formula (A), or a pharma- ceutically acceptable salt, enantiomer, diastereomer, or racemate thereof; and (b) a pharma- ceutically acceptable vector; Formula (A): 【Chemistry 1】 Where: * denotes that the stereochemical isomerism of the carbon atoms is, independently, R and / or S; R1 is selected from the group consisting of substituted or unsubstituted C1-C4 alkyl groups, substituted or unsubstituted C3-C6 cycloalkyl groups, substituted or unsubstituted C3-C6 cycloalkyl C1 alkylene groups, and substituted or unsubstituted C6 aryl C1 alkylene groups; R 2 is selected from the group consisting of hydrogen, a C1 alkyl group; R ３ is selected from the group consisting of a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 cycloalkyl C1-C5 alkylene group, a substituted or unsubstituted C6-C10 aryl group, and a substituted or unsubstituted C6-C10 aryl C1-C5 alkylene group; R ４ is a substituted or unsubstituted quinoxalinyl group, a substituted or unsubstituted quinazolinyl group, a substituted or unsubstituted cinnolinyl group, a substituted or unsubstituted indolyl group, a substituted or unsubstituted isoindolyl group, a substituted or unsubstituted benzimidazolyl group, a substituted or unsubstituted indazolyl group, a substituted or unsubstituted imidazo[1,2-A]pyridyl group, a substituted or unsubstituted imidazo[1,5-A]pyridyl group, a substituted or unsubstituted quinolyl group, a substituted or unsubstituted substituted isoquinolyl group, substituted or unsubstituted benzothienyl group, substituted or unsubstituted benzofuranyl group, where substituted refers to the replacement of a hydrogen atom on the group by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, hydroxyl group, C1-C6 alkyl group, halogenated C1-C6 alkyl group, C1-C6 alkoxy group, halogenated C1-C6 alkoxy group, and C1-C6 alkylthio group; R ６ is hydrogen, -NR ５ adjacent to it is —(C═O)—CH ２ When forming a ring with -, R ５ is -(CH ２ ) ｎ -, n is 2 or 3, -NR ５ adjacent to it is —(C═O)—CH ２ When R does not form a ring with -, ５ is selected from the group consisting of hydrogen, a C1-C6 alkyl group, and a C3-C8 cycloalkyl group; Here, R １ and R3, "substituted" refers to being substituted by 1, 2, 3 or 4 substituents each independently selected from the group consisting of a halogen, a cyano group, a C1-C6 alkyl group, and a halogenated C1-C6 alkyl group; Pharmaceutical compositions.

2. The pharmaceutical composition of claim 1, wherein the associated disease caused by the 2019 novel coronavirus infection is selected from the group consisting of respiratory infections, pneumonia and its complications, and combinations thereof.

3. R1 is selected from the group consisting of a C1-C4 alkyl group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkyl C1 alkylene group, and a C6 aryl C1 alkylene group; R 2 is selected from the group consisting of hydrogen, a C1 alkyl group; R ３ is selected from the group consisting of a C1-C6 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl C1-C5 alkylene group, and a substituted or unsubstituted C6-C10 aryl C1-C5 alkylene group; where R and R ３ In the formula, "substituted" refers to substitution with 1, 2 or 3 substituents, each of which is independently selected from the group consisting of halogen and C1-C6 alkyl groups; The pharmaceutical composition of claim 1.

4. The pharmaceutical composition according to claim 1, wherein R 1 is selected from the group consisting of a C3-C6 cycloalkyl group and a C6 aryl C1 alkylene group.

5. The pharmaceutical composition according to claim 1, wherein R 3 is selected from the group consisting of a C3-C8 cycloalkyl C1-C5 alkylene group, and a substituted or unsubstituted C6-C10 aryl C1-C5 alkylene group.

6. -NR ５ and adjacent -(C=O)-CH ２ - forms a ring, and R ５ is -(CH ２ ) ｎ - and n is 2 or 3.

7. R ４ teeth, a substituted or unsubstituted quinoxalinyl group, a substituted or unsubstituted indolyl group; a substituted or unsubstituted benzimidazolyl group; a substituted or unsubstituted imidazo[1,2-a]pyridyl group; a substituted or unsubstituted quinolyl group; a substituted or unsubstituted benzothienyl group, Substituted or unsubstituted benzofuranyl groups is selected from the group consisting of Here, the term "substitution" refers to the substitution of a hydrogen atom on the group with one, two or three substituents selected from the group consisting of F, Cl, Br, I, a hydroxyl group, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group, a C1-C6 alkoxy group, a halogenated C1-C6 alkoxy group, and a C1-C6 alkylthio group; The pharmaceutical composition of claim 1.

8. The compound is selected from the group consisting of: 【Table 1-1】 【Table 1-2】 【Table 1-3】 【Table 1-4】 【Table 1-5】 【Table 1-6】 【Table 1-7】 【Table 1-8】 【Table 1-9】 【Table 1-10】 【Table 1-11】 【Table 1-12】 【Table 1-13】 【Table 1-14】 【Table 1-15】 【Table 1-16】 【Table 1-17】 【Table 1-18】 【Table 1-19】 【Table 1-20】 【Table 1-21】 【Table 1-22】 【Table 1-23】 【Table 1-24】 【Table 1-25】 【Table 1-26】 【Table 1-27】 【Table 1-28】 【Table 1-29】 【Table 1-30】 【Table 1-31】 【Table 1-32】 【Table 1-33】 【Table 1-34】 【Table 1-35】 【Table 1-36】 【Table 1-37】 The pharmaceutical composition of claim 1.

9. A compound of formula (A) or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate thereof, Formula (A): 【Chemistry 2】 Where: * denotes that the stereochemical isomerism of the carbon atoms is, independently, R and / or S; R1 is selected from the group consisting of substituted or unsubstituted C1-C4 alkyl groups, substituted or unsubstituted C3-C6 cycloalkyl groups, substituted or unsubstituted C3-C6 cycloalkyl C1 alkylene groups, and substituted or unsubstituted C6 aryl C1 alkylene groups; R 2 is selected from the group consisting of hydrogen, a C1 alkyl group; R ３ is selected from the group consisting of a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 cycloalkyl C1-C5 alkylene group, a substituted or unsubstituted C6-C10 aryl group, and a substituted or unsubstituted C6-C10 aryl C1-C5 alkylene group; R ４ is a substituted or unsubstituted quinoxalinyl group, a substituted or unsubstituted quinazolinyl group, a substituted or unsubstituted cinnolinyl group, a substituted or unsubstituted indolyl group, a substituted or unsubstituted isoindolyl group, a substituted or unsubstituted benzimidazolyl group, a substituted or unsubstituted indazolyl group, a substituted or unsubstituted imidazo[1,2-A]pyridyl group, a substituted or unsubstituted imidazo[1,5-A]pyridyl group, a substituted or unsubstituted quinolyl group, a substituted or unsubstituted substituted isoquinolyl group, substituted or unsubstituted benzothienyl group, substituted or unsubstituted benzofuranyl group, where substituted refers to the replacement of a hydrogen atom on the group by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, hydroxyl group, C1-C6 alkyl group, halogenated C1-C6 alkyl group, C1-C6 alkoxy group, halogenated C1-C6 alkoxy group, and C1-C6 alkylthio group; R ６ is hydrogen, -NR ５ adjacent to it is —(C═O)—CH ２ When forming a ring with -, R ５ is -(CH ２ ) ｎ -, n is 2 or 3, -NR ５ adjacent to it is —(C═O)—CH ２ When R does not form a ring with -, ５ is selected from the group consisting of hydrogen, a C1-C6 alkyl group, and a C3-C8 cycloalkyl group; Here, R １ and R3, "substituted" refers to being substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, cyano group, C1-C6 alkyl group, and halogenated C1-C6 alkyl group; The compound is not one of the compounds A1-A253 defined in claim 8. A compound of formula (A) or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate thereof.

10. The compound according to claim 9, characterized in that the compound is compound A254-A257, A259-A261, A263-A267, A269-A272, A274, A276-A279, A281-A291, A293, A295-A298, A300-A301, A304-A310 as defined in claim 8, or a pharma- ceutically acceptable salt, enantiomer, diastereomer or racemate thereof.

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