NEW GLUTAMINE ANALOGUES

Description

Cross Reference To Related Applications

[0001] The application claims the benefit of PCT application Ser. No. PCT / CN2020 / 121114 filed on Oct. 15, 2020; PCT application Ser. No. PCT / CN2021 / 072111 filed on Jan. 15, 2021; and PCT application Ser. No. PCT / CN2021 / 076491 filed on Feb. 10, 2021. Technical Field

[0002] The invention relates to a novel glutamine analogs, a composition containing the glutamine analogs and the use thereof.Background Art

[0003] Glutamine analogs, such as 6-diazo-5-oxo-L-norleucine (DON) have been shown to exhibit anticancer activities. However, the occurrence of severe toxicity (e.g., dose limiting GI toxicities, such as oral mucositis, gastric bleeding, nausea and vomiting, and abdominal pain) has hampered their clinical development when administering such glutamine antagonists at therapeutic dose levels.

[0004] WO2017 / 023774, WO2017 / 023787 and WO2019 / 071110 disclose glutamine antagonists.

[0005] Prior attempts to mitigate the severe toxicity associated with glutamine antagonists such as DON, have been unsuccessful. Therefore, it's needed to develop novel glutamine antagonists to meet the clinical needs.Summary of Invention

[0006] The invention is set out in the appended set of claims. Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, and VIII are not encompassed by the wording of the claims but are considered as useful for understanding the invention. The references to the methods of treatment by therapy or surgery or in vivo diagnosis methods of this description are to be interpreted as references to compounds, pharmaceutical compositions and medicaments of the present invention for use in those methods.

[0007] In one aspect, provided here is a compound of formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, and an isotopic substitution thereof: wherein, Z is OR 1 or SR 1 ; R 1 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-6 alkyl, C 1-6 alkoxy, -C 3-8 cycloalkyl, -C 0-6 alkylene-C 3-8 heterocyclyl, -C 0-6 alkylene-NH-C 0-6 alkylene C 6-10 aryl, -C 0-6 alkylene-NH-C 0-6 alkylene-5-12 membered heteroaryl, -C 0-6 alkylene-C 6-10 aryl and -C 0-6 alkylene-5-12 membered heteroaryl; and each of which can be optional substituted with one or more substituents independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , -NH-C 3-8 cycloalkyl, carboxyl, -CO-C 1-6 alkyl; each of the heteroaryl and heterocyclyl contains 1, 2 or 3 heteroatoms selected from N, O or S; X is selected from the group consisting of hydrogen, deuterium, C 1-6 alkyl, -C(=O)-G, -C(=O)-W-(CR X1 R X2 ) m -O-R X3 , -C(=O)-W-(CR X1 R X2 ) m -S-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO 2 -R X3 , -C(=O)-W-(CR X1 R X2 ) m -G, -C(=O)-W-(C RX1 R X2 ) m -NR 5 R 5 ', -P(=O)(OR 6 ) p (NHR 7 ) q , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-R 8 , -C(=O)-W-(CR X1 R X2 ) m -G-O-R 8 , -C(=O)-O-(CR X1 R X2 ) m -O-C(=O)-R 9 , - C(=O)-O-R 7 , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-G, and -C(=O)-W-(CR X1 R X2 ) m -G-NR 5 R 5 '; W is oxygen, CO or a bond; m is selected from 1, 2, 3, 4, 5, 6, 7 or 8; p and q are each independently selected from 0,1 or 2 provided that the sum of p and q is 2; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CN, OH, NH 2 , C 1-6 alkyl, C 1-6 alkoxy, C 4-10 cycloalkyl, -C(=O)-C 1-6 alkyl, C 5-12 aryl, -C 1-6 alkylene-C 5-12 aryl, -5-12 membered heteroaryl, and -C 1-6 alkylene-5-12 membered heteroaryl, and wherein said C 1-6 alkyl, said C 1-6 alkoxy, said C 4-10 cycloalkyl, said C 5-12 aryl, said-C 1-6 alkylene-C 5-12 aryl, said -5-12 membered heteroaryl, and said-C 1-6 alkylene-5-12 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , -S- C 1-6 alkyl, carboxyl; and each of the heteroaryl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; or R X1 and R X2 together with the carbon atom to which they are attached form C 3-10 carbocyclic ring, C 3-10 membered heterocyclyl, and each of the heterocyclyl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -NH 2 , -CN, -OH, -NO 2 , carbonyl, =O. oxo, carboxyl, C 1-6 alkoxy, C 1-6 alkyl; R X3 is independently selected from the group consisting of hydrogen, deuterium, C 1-6 alkyl, C 1-6 alkoxy, C 3-8 cycloalkyl, -C(=O)-C 1-6 alkyl, and -C 1-6 alkylenen-C 5-12 aryl, wherein said C 1-6 alkyl, said C 1-6 alkoxy, said C 3-8 cycloalkyl, said -C(=O)-C 1-6 alkyl, and said -C 1-6 alkylenen-C 5-12 aryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl, 4-8 membered heterocyclyl, -C 6-12 aryl, -C(=O)-C 1-6 alkyl, -NH-C(=O)-C 1-6 alkyl, -C(=O)-NH 2 , -C(=O)-NH-C 1-6 alkyl, and - C(=O)-N(C 1-6 alkyl) 2 ; or R X1 and R X3 together with the carbon atom and the oxygen atom to which they are attached respectively form a 5-12 membered heterocyclyl, wherein said 5-12 membered heterocyclyl can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; and each of the heterocyclyl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; R 5 and R 5 ' are each independently selected from the group consisting of hydrogen, deuterium, - C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, C 5-12 aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclyl, and wherein said -C 1-6 alkyl, said -C 1-6 alkoxy, said -C 3-8 cycloalkyl, said C 5-12 aryl, said 5-12 membered heteroaryl, said 5-12 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; each of R 6 is independently selected from the group consisting of hydrogen, deuterium, -C 1-6 alkyl, -C 3-8 cycloalkyl, 5-12 membered heterocyclyl ring, -C 1-6 alkenyl, and -C 3-8 cycloalkenyl, and wherein said -C 1-6 alkyl, said -C 3-8 cycloalkyl, said 5-12 membered heterocyclyl ring, said -C 1-6 alkenyl, and said -C 3-8 cycloalkenyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, - CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; or R 6 together with the oxygen atom to which it is attached forms a purine or pyrimidine nucleoside; each of R 7 is independent selected from the group consisting of hydrogen, deuterium, halogen, C 1-6 alkyl, C 3-8 cycloalkyl, 5-12 membered heterocyclyl ring, C 1-6 alkenyl, C 3-8 cycloalkenyl, C 5-12 aryl, and 5-12 membered heteroaryl, and wherein said C 1-6 alkyl, said C 3-8 cycloalkyl, said 5-12 membered heterocyclyl ring, said C 1-6 alkenyl, said C 3-8 cycloalkenyl, said C 5-12 aryl, and said 5-12 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; R 8 and R 9 are each independently selected from the group consisting of C 1-6 alkyl, C 3-8 cycloalkyl, monosaccharide, acylated monosaccharide, C 5-12 aryl, and 5-12 membered heteroaryl, and wherein said C 1-6 alkyl, said C 3-8 cycloalkyl, said monosaccharide, said acylated monosaccharide, said C 5-12 aryl, and said 5-12 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, - OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; G is C 5-12 aryl, or 5-12 membered heteroaryl, wherein C 5-12 aryl, and 5-12 membered heteroaryl can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; R 2 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl, and said C 1-6 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; R 3 and R 3 ' are each independently selected from the group consisting of hydrogen, deuterium, halogen, C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl, and said C 1-6 alkoxy can be optional substituted with one or more substituents, which are independently from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; Y is a bond, oxygen, or -(CR Y1 R Y2 ) n -; n is selected from 1, 2, 3, 4, 5, 6, 7 or 8; R Y1 and R Y2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl, and said C 1-6 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; R 4 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl, and said C 1-6 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; R 10 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl, and said C 1-6 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl.

[0008] In some embodiments of the compound of Formula I, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereofe of the present invention, wherein the compound is of formula I-A:

[0009] In some embodiments of the compound of Formula I, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereofe of the present invention, wherein the compound is of formula I-B:

[0010] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, C 1-3 alkoxy, -C 3-8 cycloalkyl, -C 0-3 alkylene-C 3-8 heterocyclyl, -C 0-3 alkylene-NH-C 0-3 alkylene C 6-10 aryl, -C 0-3 alkylene-NH-C 0-3 alkylene-5-12membered heteroaryl, -C 0-3 alkylene-C 6-10 aryl and -C 0-3 alkylene-5-12 membered heteroaryl; and each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, - C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -NH-C 3-8 cycloalkyl, -N(C 1-6 alkyl) 2 , carboxyl, -CO-C 1-6 alkyl; each of the heteroaryl and heterocyclyl contains 1 or 2 heteroatoms selected from N, O or S.

[0011] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, C 1-3 alkoxy, -C 3-8 cycloalkyl, -C 0-3 alkylene-C 3-8 heterocyclyl, -C 0-3 alkylene-NH-C 0-3 alkylene C 6-10 aryl, -C 0-3 alkylene-NH-C 0-3 alkylene-5-12 membered heteroaryl, -C 0-3 alkylene-C 6-10 aryl and -C 0-3 alkylene-5-12 membered heteroaryl; each of the heteroaryl and heterocyclyl contains 1 or 2 heteroatoms selected from N or O; and wherein each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, - C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -NH-C 3-6 cycloalkyl, -N(C 1-3 alkyl) 2 , carboxyl, -CO-C 1-3 alkyl; each of the heteroaryl and heterocyclyl contains 1 or 2 heteroatoms selected from N or O.

[0012] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, and each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -NH-C 3-6 cycloalkyl, -N(C 1-3 alkyl) 2 , carboxyl, -CO-C 1-3 alkyl.

[0013] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, and each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , -NH-cyclopropyl, -NH-cyclobutyl, -NH-cyclopentyl, -NH-cyclohexyl, carboxyl and -CO-tert-butyl.

[0014] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is seleted from hydrogen, deuterium, isopropyl, methyl, ethyl, -tert-butyl, -CF 3 , - CH 2 CF 3 , -CH(CH 3 )CF 3 , -CH(CH 3 )CH 2 CF 3 , -(CH 2 ) 2 CF 3 , -(CH 2 ) 2 -CH(CH 3 ) 2 , -C(CH 3 ) 2 CF 3 , - C(CH 3 ) 2 CH 2 CF 3 , -CN, -CH 2 CN,-CH(CH 3 )CN,-CH 2 CH 2 CN, -CH(CH 3 )CH 2 CN, -C(CH 3 ) 2 CN, - C(CH 3 ) 2 CH 2 CN,-CH 2 OH,-CH 2 -O-CH 3 , -CH 2 -O-CH 2 CH 3 , -CH 2 -O-CH(CH 3 ) 2 ,

[0015] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein X is selected from the group consisting of hydrogen, deuterium, C 1-6 alkyl, -C(=O)-G, -C(=O)-W-(CR X1 R X2 ) m -O-R X3 , -C(=O)-W-(CR X1 R X2 ) m -S-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO 2 -R X3 , -C(=O)-W-(CR X1 R X2 ) m -G, -C(=O)-W-(CR X1 R X2 ) m -NR 5 R 5 ', - P(=O)(OR 6 ) p (NHR 7 ) q , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-R 8 , -C(=O)-W-(CR X1 R X2 ) m -G-O-R 8 , - C(=O)-O-(CR X1 R X2 ) m -O-C(=O)-R 9 , -C(=O)-O-R 7 , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-G, and - C(=O)-W-(CR X1 R X2 ) m- G-NR 5 R 5 '; W is oxygen, CO or a bond; m is selected from 1, 2 or 3; p and q are each independently selected from 0, 1 or 2 provided that the sum of p and q is 2; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CN, OH, C 1-4 alkyl, C 1-3 alkoxy, C 4-8 cycloalkyl, -C(=O)-C 1-3 alkyl, C 5-10 aryl, -C 1-3 alkylene-C 5-10 aryl, 5-10 membered heteroaryl, and -C 1-3 alkylene-5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 1-3 alkoxy, said C 4-8 cycloalkyl, said C 5-10 aryl, said -C 1-3 alkylene-C 5-10 aryl, said 5-10 membered heteroaryl, and said -C 1-3 alkylene-5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , -S- C 1-6 alkyl or carboxyl; and each of the heteroaryl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; or R X1 and R X2 together with the carbon atom to which they are attached form C 4-8 carbocyclic ring, C 4-8 membered heterocyclyl, and each of the heterocyclyl independently optionally contains 1,2 or 3 heteroatoms selected from N, O or S; each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, - NH 2 , -CN, -OH, -NO 2 , carbonyl, =O, oxo, carboxyl, C 1-6 alkoxy, C 1-6 alkyl; R X3 is independently selected from the group consisting of hydrogen, deuterium, C 1-3 alkyl, C 1-3 alkoxy, C 3-6 cycloalkyl, -C(=O)-C 1-3 alkyl, and -C 1-3 alkylenen-C 5-10 aryl, wherein said C 1-3 alkyl, said C 1-3 alkoxy, said C 3-6 cycloalkyl, said -C(=O)-C 1-3 alkyl, and said -C 1-3 alkylenen-C 5-10 aryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , - NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl, 4-8 membered heterocyclyl, -C 6-12 aryl, -C(=O)-C 1-6 alkyl, -NH-C(=O)-C 1-6 alkyl, -C(=O)-NH 2 , -C(=O)-NH-C 1-6 alkyl, and -C(=O)-N(C 1-6 alkyl) 2 ; or R X1 and R X3 together with the carbon atom and the oxygen atom to which they are attached respectively form a 5-10 membered heterocyclyl, wherein said 5-10 membered heterocyclyl can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , - NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; and each of the heterocyclyl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; R 5 and R 5 ' are each independently selected from the group consisting of hydrogen, deuterium, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, C 5-10 aryl, 5-10 membered heteroaryl, 5-10 membered heterocyclyl, and wherein said -C 1-3 alkyl, -C 1-3 alkoxy, said -C 3-6 cycloalkyl, said C 5-10 aryl, said 5-10 membered heteroaryl, said 5-10 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; each of R 6 is independently selected from the group consisting of hydrogen, deuterium, -C 1-3 alkyl, - C 3-6 cycloalkyl, 5-10 membered heterocyclyl ring, -C 1-3 alkenyl, and -C 3-6 cycloalkenyl, and wherein said -C 1-3 alkyl, said -C 3-6 cycloalkyl, said 5-10 membered heterocyclyl ring, said -C 1-3 alkenyl, and said -C 3-6 cycloalkenyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; or R 6 together with the oxygen atom to which it is attached forms a purine or pyrimidine nucleoside; each of R 7 is independent selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, C 3-6 cycloalkyl, 5-10 membered heterocyclyl ring, C 1-3 alkenyl, C 3-6 cycloalkenyl, C 5-10 aryl, and 5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 3-6 cycloalkyl, said 5-10 membered heterocyclyl ring, said C 1-3 alkenyl, said C 3-6 cycloalkenyl, said C 5-10 aryl, and said 5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, - C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; R 8 and R 9 are each independently selected from the group consisting of C 1-3 alkyl, C 3-6 cycloalkyl, monosaccharide, acylated monosaccharide, C 5-10 aryl, and 5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 3-6 cycloalkyl, said monosaccharide, said acylated monosaccharide, said C 5-10 aryl, and said 5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl; or G is C 5-10 aryl, or 5-10 membered heteroaryl, wherein C 5-10 aryl, and 5-10 membered heteroaryl can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, - NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , carboxyl.

[0016] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein X is selected from the group consisting of hydrogen, deuterium, C 1-3 alkyl, -C(=O)-G, -C(=O)-W-(CR X1 R X2 ) m -O-R X3 , -C(=O)-W-(CR X1 R X2 ) m -S-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO 2 -R X3 , -C(=O)-W-(CR X1 R X2 ) m -G, -C(=O)-W-(CR X1 R X2 ) m -NR 5 R 5 ', - P(=O)(OR 6 ) p (NHR 7 ) q , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-R 8 , -C(=O)-W-(CR X1 R X2 ) m -G-O-R 8 , - C(=O)-O-(CR X1 R X2 ) m -O-C(=O)-R 9 , -C(=O)-O-R 7 , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-G, and - C(=O)-W-(CR X1 R X2 ) m -G-NR 5 R 5 '; W is oxygen or a bond; m is selected from 1, 2 or 3; p and q are each independently selected from 0,1 or 2 provided that the sum of p and q is 2; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CN, OH, C 1-4 alkyl, C 1-3 alkoxy, C 4-8 cycloalkyl, -C(=O)-C 1-3 alkyl, C 5-10 aryl, -C 1-3 alkylene-C 5-10 aryl, 5-10 membered heteroaryl, and -C 1-3 alkylene-5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 1-3 alkoxy, said C 4-8 cycloalkyl, said C 5-10 aryl, said-C 1-3 alkylene-C 5-10 aryl, said 5-10 membered heteroaryl, and said-C 1-3 alkylene-5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-3 alkyl) 2 , -S-C 1-3 alkyl carboxyl; and each of the heteroaryl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; or R X1 and R X2 together with the carbon atom to which they are attached form C 4-6 carbocyclic ring, C 4-6 membered heterocyclyl, and each of the heterocyclyl independently optionally contains 1,2 or 3 heteroatoms selected from N, O or S; each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, - NH 2 , -CN, -OH, -NO 2 , oxo, carboxyl, C 1-3 alkoxy, C 1-3 alkyl; R X3 is independently selected from the group consisting of hydrogen, deuterium, C 1-3 alkyl, C 1-3 alkoxy, C 3-6 cycloalkyl, -C(=O)-C 1-3 alkyl, and -C 1-3 alkylenen-C 5-10 aryl, wherein said C 1-3 alkyl, said C 1-3 alkoxy, said C 3-6 cycloalkyl, said -C(=O)-C 1-3 alkyl, and said -C 1-3 alkylenen-C 5-10 aryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , -S- C 1-3 alkyl carboxyl, 4-6 membered heterocyclyl, -C 6-10 aryl, -C(=O)-C 1-3 alkyl, -NH-C(=O)-C 1-3 alkyl, -C(=O)-NH 2 , -C(=O)-NH-C 1-3 alkyl, -C(=O)-N(C 1-3 alkyl) 2 ; or R X1 and R X3 together with the carbon atom and the oxygen atom to which they are attached respectively form a 5-10 membered heterocyclyl, wherein said 5-10 membered heterocyclyl can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; and each of the heterocyclyl independently optionally contains 1, 2 or 3 heteroatoms selected from N, O or S; R 5 and R 5 ' are each independently selected from the group consisting of hydrogen, deuterium, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, C 5-10 aryl, 5-10 membered heteroaryl, 5-10 membered heterocyclyl, and wherein said -C 1-3 alkyl, -C 1-3 alkoxy, said -C 3-6 cycloalkyl, said C 5-10 aryl, said 5-10 membered heteroaryl, said 5-10 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; each of R 6 is independently selected from the group consisting of hydrogen, deuterium, -C 1-3 alkyl, - C 3-6 cycloalkyl, 5-10 membered heterocyclyl ring, -C 1-3 alkenyl, and -C 3-6 cycloalkenyl, and wherein said -C 1-3 alkyl, said -C 3-6 cycloalkyl, said 5-10 membered heterocyclyl ring, said -C 1-3 alkenyl, and said -C 3-6 cycloalkenyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; or R 6 together with the oxygen atom to which it is attached forms a purine or pyrimidine nucleoside; each of R 7 is independent selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, C 3-6 cycloalkyl, 5-10 membered heterocyclyl ring, C 1-3 alkenyl, C 3-6 cycloalkenyl, C 5-10 aryl, and 5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 3-6 cycloalkyl, said 5-10 membered heterocyclyl ring, said C 1-3 alkenyl, said C 3-6 cycloalkenyl, said C 5-10 aryl, and said 5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; R 8 and R 9 are each independently selected from the group consisting of C 1-3 alkyl, C 3-6 cycloalkyl, monosaccharide, acylated monosaccharide, C 5-10 aryl, and 5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 3-6 cycloalkyl, said monosaccharide, said acylated monosaccharide, said C 5-10 aryl, and said 5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, - CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; or G is C 5-10 aryl, or 5-10 membered heteroaryl, wherein C 5-10 aryl, and 5-10 membered heteroaryl can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl.

[0017] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein X is selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, - C(=O)-G, -C(=O)-W-(CR X1 R X2 ) m -O-R X3 , -C(=O)-W-(CR X1 R X2 ) m -S-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO 2 -R X3 , -C(=O)-W-(CR X1 R X2 ) m -G, -C(=O)-W-(CR X1 R X2 ) m -NR 5 R 5 ', - P(=O)(OR 6 ) p (NHR 7 ) q , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-R 8 , -C(=O)-W-(CR X1 R X2 ) m -G-O-R 8 , - C(=O)-O-(CR X1 R X2 ) m -O-C(=O)-R 9 , -C(=O)-O-R 7 , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-G, and - C(=O)-W-(CR X1 R X2 ) m- G-NR 5 R 5 '; W is oxygen or a bond; m is selected from 1, 2 or 3; p and q are each independently selected from 0,1 or 2 provided that the sum of p and q is 2; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CN, OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butyl, sec-butyl, iso-butyl, tert-butyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 , -C(=O)-CH 2 CH 2 CH 3 , -C(=O)-CH(CH 3 ) 2 , C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, -CH 2 -C 5 aryl, -CH 2 -C 6 aryl, -CH 2 -C 7 aryl, -CH 2 -C 8 aryl, -CH 2 -C 9 aryl, -CH 2 -C 10 aryl, -(CH 2 ) 2 -C 5 aryl, -(CH 2 ) 2 -C 6 aryl, -(CH 2 ) 2 -C 7 aryl, -(CH 2 ) 2 -C 8 aryl, -(CH 2 ) 2 -C 9 aryl, -(CH 2 ) 2 -C 10 aryl, -(CH 2 ) 3 -C 5 aryl, - (CH 2 ) 3 -C 6 aryl, -(CH 2 ) 3 -C 7 aryl, -(CH 2 ) 3 -C 8 aryl, -(CH 2 ) 3 -C 9 aryl, -(CH 2 ) 3 -C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, 10 membered heteroaryl, -CH 2 -5 membered heteroaryl, -CH 2 -6 membered heteroaryl, - CH 2 -7 membered heteroaryl, -CH 2 -8 membered heteroaryl, -CH 2 -9 membered heteroaryl, -CH 2 -10 membered heteroaryl, -(CH 2 ) 2 -5 membered heteroaryl, -(CH 2 ) 2 -6 membered heteroaryl, -(CH 2 ) 2 -7 membered heteroaryl, -(CH 2 ) 2 -8 membered heteroaryl, -(CH 2 ) 2 -9 membered heteroaryl, -(CH 2 ) 2 -10 membered heteroaryl, -(CH 2 ) 3 -5 membered heteroaryl, -(CH 2 ) 3 -6 membered heteroaryl, -(CH 2 ) 3 -7 membered heteroaryl, -(CH 2 ) 3 -8 membered heteroaryl, -(CH 2 ) 3 -9 membered heteroaryl, and -(CH 2 ) 3 -10 membered heteroaryl,and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said -CH 2 -C 5 aryl, said -CH 2 -C 6 aryl, said -CH 2 -C 7 aryl, said -CH 2 -C 8 aryl, said -CH 2 -C 9 aryl, said -CH 2 -C 10 aryl, said -(CH 2 ) 2 -C 5 aryl, said -(CH 2 ) 2 -C 6 aryl, said -(CH 2 ) 2 -C 7 aryl, said -(CH 2 ) 2 -C 8 aryl, said -(CH 2 ) 2 -C 9 aryl, said -(CH 2 ) 2 -C 10 aryl, said -(CH 2 ) 3 -C 5 aryl, said - (CH 2 ) 3 -C 6 aryl, said -(CH 2 ) 3 -C 7 aryl, said -(CH 2 ) 3 -C 8 aryl, said -(CH 2 ) 3 -C 9 aryl, said -(CH 2 ) 3 -C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, said 10 membered heteroaryl, said -CH 2 -5 membered heteroaryl, said -CH 2 -6 membered heteroaryl, said -CH 2 -7 membered heteroaryl, said - CH 2 -8 membered heteroaryl, said -CH 2 -9 membered heteroaryl, said -CH 2 -10 membered heteroaryl, said -(CH 2 ) 2 -5 membered heteroaryl, said -(CH 2 ) 2 -6 membered heteroaryl, said -(CH 2 ) 2 -7 membered heteroaryl, said -(CH 2 ) 2 -8 membered heteroaryl, said -(CH 2 ) 2 -9 membered heteroaryl, said -(CH 2 ) 2 -10 membered heteroaryl, said -(CH 2 ) 3 -5 membered heteroaryl, said -(CH 2 ) 3 -6 membered heteroaryl, said -(CH 2 ) 3 -7 membered heteroaryl, said -(CH 2 ) 3 -8 membered heteroaryl, said -(CH 2 ) 3 -9 membered heteroaryl, and said -(CH 2 ) 3 -10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-3 alkyl) 2 , -S-C 1-3 alkyl, carboxyl; and each of the heteroaryl independently optionally contains 1 or 2 heteroatoms selected from N, O or S; or R X1 and R X2 together with the carbon atom to which they are attached form 3-membered carbocyclic ring, 4-membered carbocyclic ring, 5-membered carbocyclic ring, or 6-membered carbocyclic ring, 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, and each of the heterocyclyl independently optionally contains 1 or 2 heteroatoms selected from N or O; each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, -F, -Cl, -Br, -I, -NH 2 , -CN, -OH, -NO 2 , oxo, carboxyl, C 1-3 alkoxy, C 1-3 alkyl; R X3 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 , -C(=O)-CH 2 CH 2 CH 3 , -C(=O)-CH(CH 3 ) 2 , -CH 2 - C 5 aryl, -(CH 2 ) 2 - C 5 aryl, -(CH 2 ) 3 - C 5 aryl, -CH 2 - C 6 aryl, -(CH 2 ) 2 - C 6 aryl, -(CH 2 ) 3 -C 6 aryl, -CH 2 - C 7 aryl, -(CH 2 ) 2 - C 7 aryl, -(CH 2 ) 3 - C 7 aryl, -CH 2 - C 8 aryl, -(CH 2 ) 2 - C 8 aryl, -(CH 2 ) 3 -C 8 aryl, -CH 2 - C 9 aryl, -(CH 2 ) 2 - C 9 aryl, -(CH 2 ) 3 - C 9 aryl, -CH 2 - C 10 aryl, -(CH 2 ) 2 - C 10 aryl, -(CH 2 ) 3 -C 10 aryl, wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said C 3 cycloalkyl, said C 4 cycloalkyl, said C 5 cycloalkyl, said C 6 cycloalkyl, said -C(=O)-CH 3 , said -C(=O)-CH 2 CH 3 , said -C(=O)-CH 2 CH 2 CH 3 , said -C(=O)-CH(CH 3 ) 2 , said -CH 2 - C 5 aryl, said -(CH 2 ) 2 - C 5 aryl, said -(CH 2 ) 3 - C 5 aryl, said -CH 2 - C 6 aryl, said - (CH 2 ) 2 - C 6 aryl, said -(CH 2 ) 3 - C 6 aryl, said -CH 2 - C 7 aryl, said -(CH 2 ) 2 - C 7 aryl, said -(CH 2 ) 3 - C 7 aryl, said -CH 2 - C 8 aryl, said -(CH 2 ) 2 - C 8 aryl, said -(CH 2 ) 3 - C 8 aryl, said -CH 2 - C 9 aryl, said -(CH 2 ) 2 - C 9 aryl, said -(CH 2 ) 3 - C 9 aryl, said -CH 2 - C 10 aryl, said -(CH 2 ) 2 - C 10 aryl, and said -(CH 2 ) 3 - C 10 aryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl, 4-6 membered heterocyclyl, -C 6-10 aryl, - C(=O)-C 1-3 alkyl, -NH-C(=O)-C 1-3 alkyl, -C(=O)-NH 2 , -C(=O)-NH-C 1-3 alkyl, and -C(=O)-N(C 1-3 alkyl) 2 ; or R X1 and R X3 together with the carbon atom and the oxygen atom to which they are attached respectively form 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, 7 membered heterocyclyl, 8 membered heterocyclyl, 9 membered heterocyclyl, 10 membered heterocyclyl, wherein said 4 membered heterocyclyl, said 5 membered heterocyclyl, said 6 membered heterocyclyl, said 7 membered heterocyclyl, said 8 membered heterocyclyl, said 9 membered heterocyclyl, said 10 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; and each of the heterocyclyl independently optionally contains 1 or 2 heteroatoms selected from N, O or S; R 5 and R 5 ' are each independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, 10 membered heteroaryl, 5 membered heterocyclyl, 6 membered heterocyclyl, 7 membered heterocyclyl, 8 membered heterocyclyl, 9 membered heterocyclyl, 10 membered heterocyclyl, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said -C 3 cycloalkyl, said -C 4 cycloalkyl, said -C 5 cycloalkyl, said -C 6 cycloalkyl, said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, said 10 membered heteroaryl, said 5 membered heterocyclyl, said 6 membered heterocyclyl, said 7 membered heterocyclyl, said 8 membered heterocyclyl, said 9 membered heterocyclyl, said 10 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; each of R 6 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, 5 membered heterocyclyl ring, 6 membered heterocyclyl ring, 7 membered heterocyclyl ring, 8 membered heterocyclyl ring, 9 membered heterocyclyl ring, 10 membered heterocyclyl ring, vinyl, allyl, -C 3 cycloalkenyl, -C 4 cycloalkenyl, -C 5 cycloalkenyl, -C 6 cycloalkenyl, and wherein said methyl, said ethyl, said propyl, said isopropyl, said -C 3 cycloalkyl, said -C 4 cycloalkyl, said -C 5 cycloalkyl, said - C 6 cycloalkyl, said 5 membered heterocyclyl ring, said 6 membered heterocyclyl ring, said 7 membered heterocyclyl ring, said 8 membered heterocyclyl ring, said 9 membered heterocyclyl ring, said 10 membered heterocyclyl ring, said vinyl, said allyl, said -C 3 cycloalkenyl, said -C 4 cycloalkenyl, said -C 5 cycloalkenyl, said -C 6 cycloalkenyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; or R 6 together with the oxygen atom to which it is attached forms a purine or pyrimidine nucleoside; each of R 7 is independent selected from the group consisting of hydrogen, deuterium, halogen, methyl, ethyl, propyl, isopropyl, C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, 5-10 membered heterocyclyl ring, 5 membered heterocyclyl ring, 6 membered heterocyclyl ring, 7 membered heterocyclyl ring, 8 membered heterocyclyl ring, 9 membered heterocyclyl ring, 10 membered heterocyclyl ring, vinyl, allyl, C 3 cycloalkenyl, C 4 cycloalkenyl, C 5 cycloalkenyl, C 6 cycloalkenyl, C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, 10 membered heteroaryl, and wherein said methyl, said ethyl, said propyl, said isopropyl, said C 3 cycloalkyl, said C 4 cycloalkyl, said C 5 cycloalkyl, said C 6 cycloalkyl, said 5-10 membered heterocyclyl ring, said 5 membered heterocyclyl ring, said 6 membered heterocyclyl ring, said 7 membered heterocyclyl ring, said 8 membered heterocyclyl ring, said 9 membered heterocyclyl ring, said 10 membered heterocyclyl ring, said vinyl, said allyl, said C 3 cycloalkenyl, said C 4 cycloalkenyl, said C 5 cycloalkenyl, said C 6 cycloalkenyl, said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, said 10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl; R 8 and R 9 are each independently selected from the group consisting of C 1-3 alkyl, C 3-6 cycloalkyl, monosaccharide, acylated monosaccharide, C 5-10 aryl, and 5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 3-6 cycloalkyl, said monosaccharide, said acylated monosaccharide, said C 5-10 aryl, and said 5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, - CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , or carboxyl; or G is C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, or 10 membered heteroaryl, wherein said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, or said 10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxyl.

[0018] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein X is selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, - C(=O)-G, -C(=O)-W-(CR X1 R X2 ) m -O-R X3 , -C(=O)-W-(CR X1 R X2 ) m -S-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO-R X3 , C(=O)-W-(CR X1 R X2 ) m -SO 2 -R X3 , -C(=O)-W-(CR X1 R X2 ) m -G, -C(=O)-W-(CR X1 R X2 ) m -NR 5 R 5 ', - P(=O)(OR 6 ) p (NHR 7 ) q , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-R 8 , -C(=O)-W-(CR X1 R X2 ) m -G-O-R 8 , - C(=O)-O-(CR X1 R X2 ) m -O-C(=O)-R 9 , -C(=O)-O-R 7 , -C(=O)-W-(CR X1 R X2 ) m -G-O-C(=O)-G, and - C(=O)-W-(CR X1 R X2 ) m -G-NR 5 R 5 '; W is oxygen or a bond; m is selected from 1, 2 or 3; p and q are each independently selected from 0,1 or 2 provided that the sum of p and q is 2; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CN, OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butyl, sec-butyl, iso-butyl, tert-butyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 , -C(=O)-CH 2 CH 2 CH 3 , -C(=O)-CH(CH 3 ) 2 , C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, -CH 2 -C 5 aryl, -CH 2 -C 6 aryl, -CH 2 -C 7 aryl, -CH 2 -C 8 aryl, -CH 2 -C 9 aryl, -CH 2 -C 10 aryl, -(CH 2 ) 2 -C 5 aryl, -(CH 2 ) 2 -C 6 aryl, -(CH 2 ) 2 -C 7 aryl, -(CH 2 ) 2 -C 8 aryl, -(CH 2 ) 2 -C 9 aryl, -(CH 2 ) 2 -C 10 aryl, -(CH 2 ) 3 -C 5 aryl, - (CH 2 ) 3 -C 6 aryl, -(CH 2 ) 3 -C 7 aryl, -(CH 2 ) 3 -C 8 aryl, -(CH 2 ) 3 -C 9 aryl, -(CH 2 ) 3 -C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, 10 membered heteroaryl, -CH 2 -5 membered heteroaryl, -CH 2 -6 membered heteroaryl, - CH 2 -7 membered heteroaryl, -CH 2 -8 membered heteroaryl, -CH 2 -9 membered heteroaryl, -CH 2 -10 membered heteroaryl, -(CH 2 ) 2 -5 membered heteroaryl, -(CH 2 ) 2 -6 membered heteroaryl, -(CH 2 ) 2 -7 membered heteroaryl, -(CH 2 ) 2 -8 membered heteroaryl, -(CH 2 ) 2 -9 membered heteroaryl, -(CH 2 ) 2 -10 membered heteroaryl, -(CH 2 ) 3 -5 membered heteroaryl, -(CH 2 ) 3 -6 membered heteroaryl, -(CH 2 ) 3 -7 membered heteroaryl, -(CH 2 ) 3 -8 membered heteroaryl, -(CH 2 ) 3 -9 membered heteroaryl, and -(CH 2 ) 3 -10 membered heteroaryl,and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said -CH 2 -C 5 aryl, said -CH 2 -C 6 aryl, said -CH 2 -C 7 aryl, said -CH 2 -C 8 aryl, said -CH 2 -C 9 aryl, said -CH 2 -C 10 aryl, said -(CH 2 ) 2 -C 5 aryl, said -(CH 2 ) 2 -C 6 aryl, said -(CH 2 ) 2 -C 7 aryl, said -(CH 2 ) 2 -C 8 aryl, said -(CH 2 ) 2 -C 9 aryl, said -(CH 2 ) 2 -C 10 aryl, said -(CH 2 ) 3 -C 5 aryl, said - (CH 2 ) 3 -C 6 aryl, said -(CH 2 ) 3 -C 7 aryl, said -(CH 2 ) 3 -C 8 aryl, said -(CH 2 ) 3 -C 9 aryl, said -(CH 2 ) 3 -C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, said 10 membered heteroaryl, said -CH 2 -5 membered heteroaryl, said -CH 2 -6 membered heteroaryl, said -CH 2 -7 membered heteroaryl, said - CH 2 -8 membered heteroaryl, said -CH 2 -9 membered heteroaryl, said -CH 2 -10 membered heteroaryl, said -(CH 2 ) 2 -5 membered heteroaryl, said -(CH 2 ) 2 -6 membered heteroaryl, said -(CH 2 ) 2 -7 membered heteroaryl, said -(CH 2 ) 2 -8 membered heteroaryl, said -(CH 2 ) 2 -9 membered heteroaryl, said -(CH 2 ) 2 -10 membered heteroaryl, said -(CH 2 ) 3 -5 membered heteroaryl, said -(CH 2 ) 3 -6 membered heteroaryl, said -(CH 2 ) 3 -7 membered heteroaryl, said -(CH 2 ) 3 -8 membered heteroaryl, said -(CH 2 ) 3 -9 membered heteroaryl, and said -(CH 2 ) 3 -10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , -NHcyclopropyl, -NH-cyclobutyl, -NH-cyclopentyl, -NH-cyclohexyl, -S-methyl and carboxyl; and each of the heteroaryl independently optionally contains 1 or 2 heteroatoms selected from N, O or S; or R X1 and R X2 together with the carbon atom to which they are attached form 3-membered carbocyclic ring, 4-membered carbocyclic ring, 5-membered carbocyclic ring, 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, and each of the heterocyclyl independently optionally contains 1 or 2 heteroatoms selected from N or O; each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, -F, -Cl, -Br, -I, -NH 2 , -CN, -OH, -NO 2 , oxo, carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy; R X3 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 , -C(=O)-CH 2 CH 2 CH 3 , -C(=O)-CH(CH 3 ) 2 , -CH 2 - C 5 aryl, -(CH 2 ) 2 - C 5 aryl, -(CH 2 ) 3 - C 5 aryl, -CH 2 - C 6 aryl, -(CH 2 ) 2 - C 6 aryl, -(CH 2 ) 3 -C 6 aryl, -CH 2 - C 7 aryl, -(CH 2 ) 2 - C 7 aryl, -(CH 2 ) 3 - C 7 aryl, -CH 2 - C 5 aryl, -(CH 2 ) 2 - C 8 aryl, -(CH 2 ) 3 -C 8 aryl, -CH 2 - C 9 aryl, -(CH 2 ) 2 - C 9 aryl, -(CH 2 ) 3 - C 9 aryl, -CH 2 - C 10 aryl, -(CH 2 ) 2 - C 10 aryl, -(CH 2 ) 3 -C 10 aryl, wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said C 3 cycloalkyl, said C 4 cycloalkyl, said C 5 cycloalkyl, said C 6 cycloalkyl, said -C(=O)-CH 3 , said -C(=O)-CH 2 CH 3 , said -C(=O)-CH 2 CH 2 CH 3 , said -C(=O)-CH(CH 3 ) 2 , said -CH 2 - C 5 aryl, said -(CH 2 ) 2 - C 5 aryl, said -(CH 2 ) 3 - C 5 aryl, said -CH 2 - C 6 aryl, said - (CH 2 ) 2 - C 6 aryl, said -(CH 2 ) 3 - C 6 aryl, said -CH 2 - C 7 aryl, said -(CH 2 ) 2 - C 7 aryl, said -(CH 2 ) 3 - C 7 aryl, said -CH 2 - C 8 aryl, said -(CH 2 ) 2 - C 8 aryl, said -(CH 2 ) 3 - C 8 aryl, said -CH 2 - C 9 aryl, said -(CH 2 ) 2 - C 9 aryl, said -(CH 2 ) 3 - C 9 aryl, said -CH 2 - C 10 aryl, said -(CH 2 ) 2 - C 10 aryl, and said -(CH 2 ) 3 - C 10 aryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, -C 6 aryl, - C(=O)-CH 3 , -NH-C(=O)-CH 3 , -C(=O)-NH 2 , -C(=O)-NH-CH 3 , -C(=O)-N(CH 3 ) 2 , -NH 2 , -NHCH 3 , - NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , - N(CH(CH 3 ) 2 ) 2 , and carboxyl; or R X1 and R X3 together with the carbon atom and the oxygen atom to which they are attached respectively form 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, 7 membered heterocyclyl, 8 membered heterocyclyl, 9 membered heterocyclyl, 10 membered heterocyclyl, wherein said 4 membered heterocyclyl, said 5 membered heterocyclyl, said 6 membered heterocyclyl, said 7 membered heterocyclyl, said 8 membered heterocyclyl, said 9 membered heterocyclyl, said 10 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl; and each of the heterocyclyl independently optionally contains 1 or 2 heteroatoms selected from N, O or S; R 5 and R 5 ' are each independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, 10 membered heteroaryl, 5 membered heterocyclyl, 6 membered heterocyclyl, 7 membered heterocyclyl, 8 membered heterocyclyl, 9 membered heterocyclyl, 10 membered heterocyclyl, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said -C 3 cycloalkyl, said -C 4 cycloalkyl, said -C 5 cycloalkyl, said -C 6 cycloalkyl, said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, said 10 membered heteroaryl, said 5 membered heterocyclyl, said 6 membered heterocyclyl, said 7 membered heterocyclyl, said 8 membered heterocyclyl, said 9 membered heterocyclyl, said 10 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl; each of R 6 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, 5 membered heterocyclyl ring, 6 membered heterocyclyl ring, 7 membered heterocyclyl ring, 8 membered heterocyclyl ring, 9 membered heterocyclyl ring, 10 membered heterocyclyl ring, vinyl, allyl, -C 3 cycloalkenyl, -C 4 cycloalkenyl, -C 5 cycloalkenyl, -C 6 cycloalkenyl, and wherein said methyl, said ethyl, said propyl, said isopropyl, said -C 3 cycloalkyl, said -C 4 cycloalkyl, said -C 5 cycloalkyl, said - C 6 cycloalkyl, said 5 membered heterocyclyl ring, said 6 membered heterocyclyl ring, said 7 membered heterocyclyl ring, said 8 membered heterocyclyl ring, said 9 membered heterocyclyl ring, said 10 membered heterocyclyl ring, said vinyl, said allyl, said -C 3 cycloalkenyl, said -C 4 cycloalkenyl, said -C 5 cycloalkenyl, said -C 6 cycloalkenyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl; or R 6 together with the oxygen atom to which it is attached forms a purine or pyrimidine nucleoside; each of R 7 is independent selected from the group consisting of hydrogen, deuterium, halogen, methyl, ethyl, propyl, isopropyl, C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, 5-10 membered heterocyclyl ring, 5 membered heterocyclyl ring, 6 membered heterocyclyl ring, 7 membered heterocyclyl ring, 8 membered heterocyclyl ring, 9 membered heterocyclyl ring, 10 membered heterocyclyl ring, vinyl, allyl, C 3 cycloalkenyl, C 4 cycloalkenyl, C 5 cycloalkenyl, C 6 cycloalkenyl, C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, 10 membered heteroaryl, and wherein said methyl, said ethyl, said propyl, said isopropyl, said C 3 cycloalkyl, said C 4 cycloalkyl, said C 5 cycloalkyl, said C 6 cycloalkyl, said 5-10 membered heterocyclyl ring, said 5 membered heterocyclyl ring, said 6 membered heterocyclyl ring, said 7 membered heterocyclyl ring, said 8 membered heterocyclyl ring, said 9 membered heterocyclyl ring, said 10 membered heterocyclyl ring, said vinyl, said allyl, said C 3 cycloalkenyl, said C 4 cycloalkenyl, said C 5 cycloalkenyl, said C 6 cycloalkenyl, said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, said 10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , - NHCH 3 , -NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , - N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl; R 8 and R 9 are each independently selected from the group consisting of C 1-3 alkyl, C 3-6 cycloalkyl, monosaccharide, acylated monosaccharide, C 5-10 aryl, and 5-10 membered heteroaryl, and wherein said C 1-3 alkyl, said C 3-6 cycloalkyl, said monosaccharide, said acylated monosaccharide, said C 5-10 aryl, and said 5-10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, - CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , - NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl; or G is C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, or 10 membered heteroaryl, wherein said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, or said 10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , - N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl.

[0019] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein X is -C(=O)-W-(CR X1 R X2 ) m -O-R X3 ; W is a bond; m is 1 or 2; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CN, OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butyl, sec-butyl, iso-butyl, tert-butyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 , -C(=O)-CH 2 CH 2 CH 3 , -C(=O)-CH(CH 3 ) 2 , C 5 aryl, C 6 aryl, C 7 aryl, C 8 aryl, C 9 aryl, C 10 aryl, -CH 2 -C 5 aryl, -CH 2 -C 6 aryl, -CH 2 -C 7 aryl, -CH 2 -C 8 aryl, -CH 2 -C 9 aryl, -CH 2 -C 10 aryl, -(CH 2 ) 2 -C 5 aryl, -(CH 2 ) 2 -C 6 aryl, -(CH 2 ) 2 -C 7 aryl, -(CH 2 ) 2 -C 8 aryl, -(CH 2 ) 2 -C 9 aryl, -(CH 2 ) 2 -C 10 aryl, -(CH 2 ) 3 -C 5 aryl, - (CH 2 ) 3 -C 6 aryl, -(CH 2 ) 3 -C 7 aryl, -(CH 2 ) 3 -C 8 aryl, -(CH 2 ) 3 -C 9 aryl, -(CH 2 ) 3 -C 10 aryl, 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl, 10 membered heteroaryl, -CH 2 -5 membered heteroaryl, -CH 2 -6 membered heteroaryl, - CH 2 -7 membered heteroaryl, -CH 2 -8 membered heteroaryl, -CH 2 -9 membered heteroaryl, -CH 2 -10 membered heteroaryl, -(CH 2 ) 2 -5 membered heteroaryl, -(CH 2 ) 2 -6 membered heteroaryl, -(CH 2 ) 2 -7 membered heteroaryl, -(CH 2 ) 2 -8 membered heteroaryl, -(CH 2 ) 2 -9 membered heteroaryl, -(CH 2 ) 2 -10 membered heteroaryl, -(CH 2 ) 3 -5 membered heteroaryl, -(CH 2 ) 3 -6 membered heteroaryl, -(CH 2 ) 3 -7 membered heteroaryl, -(CH 2 ) 3 -8 membered heteroaryl, -(CH 2 ) 3 -9 membered heteroaryl, and -(CH 2 ) 3 -10 membered heteroaryl,and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said C 5 aryl, said C 6 aryl, said C 7 aryl, said C 8 aryl, said C 9 aryl, said C 10 aryl, said -CH 2 -C 5 aryl, said -CH 2 -C 6 aryl, said -CH 2 -C 7 aryl, said -CH 2 -C 8 aryl, said -CH 2 -C 9 aryl, said -CH 2 -C 10 aryl, said -(CH 2 ) 2 -C 5 aryl, said -(CH 2 ) 2 -C 6 aryl, said -(CH 2 ) 2 -C 7 aryl, said -(CH 2 ) 2 -C 8 aryl, said -(CH 2 ) 2 -C 9 aryl, said -(CH 2 ) 2 -C 10 aryl, said -(CH 2 ) 3 -C 5 aryl, said - (CH 2 ) 3 -C 6 aryl, said -(CH 2 ) 3 -C 7 aryl, said -(CH 2 ) 3 -C 8 aryl, said -(CH 2 ) 3 -C 9 aryl, said -(CH 2 ) 3 -C 10 aryl, said 5 membered heteroaryl, said 6 membered heteroaryl, said 7 membered heteroaryl, said 8 membered heteroaryl, said 9 membered heteroaryl, said 10 membered heteroaryl, said -CH 2 -5 membered heteroaryl, said -CH 2 -6 membered heteroaryl, said -CH 2 -7 membered heteroaryl, said - CH 2 -8 membered heteroaryl, said -CH 2 -9 membered heteroaryl, said -CH 2 -10 membered heteroaryl, said -(CH 2 ) 2 -5 membered heteroaryl, said -(CH 2 ) 2 -6 membered heteroaryl, said -(CH 2 ) 2 -7 membered heteroaryl, said -(CH 2 ) 2 -8 membered heteroaryl, said -(CH 2 ) 2 -9 membered heteroaryl, said -(CH 2 ) 2 -10 membered heteroaryl, said -(CH 2 ) 3 -5 membered heteroaryl, said -(CH 2 ) 3 -6 membered heteroaryl, said -(CH 2 ) 3 -7 membered heteroaryl, said -(CH 2 ) 3 -8 membered heteroaryl, said -(CH 2 ) 3 -9 membered heteroaryl, and said -(CH 2 ) 3 -10 membered heteroaryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , -NHcyclopropyl, -NH-cyclobutyl, -NH-cyclopentyl, -NH-cyclohexyl, -S-methyl and carboxyl; and each of the heteroaryl independently optionally contains 1 or 2 heteroatoms selected from N, O or S; or R X1 and R X2 together with the carbon atom to which they are attached form 3-membered carbocyclic ring, 4-membered carbocyclic ring, 5-membered carbocyclic ring, 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, and each of the heterocyclyl independently optionally contains 1 or 2 heteroatoms selected from N or O; each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy; or R X3 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 , -C(=O)-CH 2 CH 2 CH 3 , -C(=O)-CH(CH 3 ) 2 , -CH 2 - C 5 aryl, -(CH 2 ) 2 - C 5 aryl, -(CH 2 ) 3 - C 5 aryl, -CH 2 - C 6 aryl, -(CH 2 ) 2 - C 6 aryl, -(CH 2 ) 3 -C 6 aryl, -CH 2 - C 7 aryl, -(CH 2 ) 2 - C 7 aryl, -(CH 2 ) 3 - C 7 aryl, -CH 2 - C 8 aryl, -(CH 2 ) 2 - C 8 aryl, -(CH 2 ) 3 -C 8 aryl, -CH 2 - C 9 aryl, -(CH 2 ) 2 - C 9 aryl, -(CH 2 ) 3 - C 9 aryl, -CH 2 - C 10 aryl, -(CH 2 ) 2 - C 10 aryl, -(CH 2 ) 3 -C 10 aryl, wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, said isopropoxy, said C 3 cycloalkyl, said C 4 cycloalkyl, said C 5 cycloalkyl, said C 6 cycloalkyl, said -C(=O)-CH 3 , said -C(=O)-CH 2 CH 3 , said -C(=O)-CH 2 CH 2 CH 3 , said -C(=O)-CH(CH 3 ) 2 , said -CH 2 - C 5 aryl, said -(CH 2 ) 2 - C 5 aryl, said -(CH 2 ) 3 - C 5 aryl, said -CH 2 - C 6 aryl, said - (CH 2 ) 2 - C 6 aryl, said -(CH 2 ) 3 - C 6 aryl, said -CH 2 - C 7 aryl, said -(CH 2 ) 2 - C 7 aryl, said -(CH 2 ) 3 - C 7 aryl, said -CH 2 - C 8 aryl, said -(CH 2 ) 2 - C 8 aryl, said -(CH 2 ) 3 - C 8 aryl, said -CH 2 - C 9 aryl, said -(CH 2 ) 2 - C 9 aryl, said -(CH 2 ) 3 - C 9 aryl, said -CH 2 - C 10 aryl, said -(CH 2 ) 2 - C 10 aryl, and said -(CH 2 ) 3 - C 10 aryl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, -C 6 aryl, - C(=O)-CH 3 , -NH-C(=O)-CH 3 , -C(=O)-NH 2 , -C(=O)-NH-CH 3 , -C(=O)-N(CH 3 ) 2 , -NH 2 , -NHCH 3 , - NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , - N(CH(CH 3 ) 2 ) 2 , and carboxyl; or R X1 and R X3 together with the carbon atom and the oxygen atom to which they are attached respectively form 4 membered heterocyclyl, 5 membered heterocyclyl, 6 membered heterocyclyl, 7 membered heterocyclyl, 8 membered heterocyclyl, 9 membered heterocyclyl, 10 membered heterocyclyl, wherein said 4 membered heterocyclyl, said 5 membered heterocyclyl, said 6 membered heterocyclyl, said 7 membered heterocyclyl, said 8 membered heterocyclyl, said 9 membered heterocyclyl, said 10 membered heterocyclyl, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl; and each of the heterocyclyl independently optionally contains 1 or 2 heteroatoms selected from N, O or S.

[0020] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein X is -C(=O)-W-(CR X1 R X2 ) m -O-R X3 ; W is a bond; m is 1 or 2; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, CN, CF 3 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butyl, sec-butyl, iso-butyl, tert-butyl, cyclobutyl, cyclopentyl, -C(=O)-CH 3 , and each of which is independently optionally subsitituted with deuterium, -F, -Cl, -Br, -I, -NH 2 , -CN, -OH, oxo, carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -NHmethyl, -NHethyl, -NHpropyl, -NHcyclopropyl, -NHisopropyl, -N(CH 3 ) 2 , -NH-cyclobutyl, - NH-cyclopentyl, -NH-cyclohexyl, or -S-methyl; or R X1 and R X2 together with the carbon atom to which they are attached form or R X3 is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, tert-butyl, -CD 3 , -C(=O)-CH 2 -CN, -C(=O)-C(CH 3 ) 3 , -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 , -C(=O)-NH-CH 3 , - C(=O)-CH 2 -N(CH 3 ) 2 , -CH 2 -C(=O)-CH 3 , -CH 2 -C(=O)-NHCH 3 , -CH 2 -C(=O)-N(CH 3 ) 2 , -CH 2 -NH 2 , - CH 2 -NH-CH 3 , -CH 2 CH 2 -OH, -CH 2 CH 2 -CN, -CH 2 -CN, -CH 2 CH 2 -C(=O)-NH 2 , -CH 2 CH 2 - C(=O)-NH-CH 3 , -CH 2 CH 2 -NH-C(=O)-CH 3 , or R X1 and R X3 together with the carbon atom and the oxygen atom to which they are attached respectively form

[0021] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein X is -C(=O)-CR X1 R X2 -O-R X3 ; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, CN, CF 3 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butyl, sec-butyl, iso-butyl, tert-butyl, cyclobutyl, cyclopentyl, -C(=O)-CH 3 , -CH 2 - cyclopropyl, -CH 2 - cyclobutyl, -CH 2 -cyclopentyl, -CH 2 -cyclohexyl, or R X3 is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, tert-butyl,-CD 3 , -C(=O)-CH 2 -CN, -C(=O)-C(CH 3 ) 3 , -C(=O)-CH 3 , -C(=O)-CH 2 CH 3 ,

[0022] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 2 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , and carboxyl.

[0023] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 2 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , and carboxyl.

[0024] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 2 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), - N(C 1-3 alkyl) 2 , and carboxyl.

[0025] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 2 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -Cs cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , -N(CH(CH 3 ) 2 ) 2 , and carboxyl. Preferably, R 2 is selected from hydrogen or deuterium.

[0026] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 3 and R 3 ' are each independently selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , and carboxyl.

[0027] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 3 and R 3 ' are each independently selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), - N(C 1-3 alkyl) 2 , and carboxyl.

[0028] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 3 and R 3 ' are each independently selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, - NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , and carboxyl.

[0029] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 3 and R 3 ' are each independently selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -Cs cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , - N(CH(CH 3 ) 2 ) 2 , and carboxyl. Preferably, R 3 and R 3 ' are each independently selected from hydrogen or deuterium.

[0030] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein Y is a bond, or -(CR Y1 R Y2 ) n -; n is selected from 1, 2, or 3; R Y1 and R Y2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , and carboxyl.

[0031] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein Y is a bond, or -(CR Y1 R Y2 ) n -; n is selected from 1, 2, or 3; R Y1 and R Y2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , and carboxyl.

[0032] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein Y is a bond, or -(CR Y1 R Y2 ) n -; n is selected from 1, 2, or 3; R Y1 and R Y2 are each independently selected from the group consisting of F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , and carboxyl.

[0033] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein Y is a bond, or -(CR Y1 R Y2 ) n -; n is selected from 1, 2, or 3; R Y1 and R Y2 are each independently selected from the group consisting of F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , - NHCH 3 , -NHCH 2 CH 3 , -NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , and -N(CH(CH 3 ) 2 ) 2 , and carboxyl.

[0034] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein Y is -CH 2 -.

[0035] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 4 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , and carboxyl.

[0036] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 4 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , and carboxyl.

[0037] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 4 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), - N(C 1-3 alkyl) 2 , and carboxyl.

[0038] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 4 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , and -N(CH(CH 3 ) 2 ) 2 , and carboxyl. Preferably, R 4 is selected from hydrogen or deuterium.

[0039] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 10 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, halogen, -OH, oxo, -CN, -C 1-6 alkyl, -C 1-6 alkoxy, -C 3-8 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-6 alkyl) 2 , and carboxyl.

[0040] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 10 is selected from the group consisting of hydrogen, deuterium, halogen, C 1-3 alkyl, and C 1-3 alkoxy, and wherein said C 1-3 alkyl, and said C 1-3 alkoxy can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, - OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , and carboxyl.

[0041] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 10 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), - N(C 1-3 alkyl) 2 , and carboxyl.

[0042] In some embodiments of the compound of Formula I, I-A, I-B, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 10 is selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy, and wherein said methyl, said ethyl, said propyl, said isopropyl, said methoxy, said ethoxy, said propoxy, and said isopropoxy, can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -C 3 cycloalkyl, -C 4 cycloalkyl, -C 5 cycloalkyl, -C 6 cycloalkyl, -NH 2 , -NHCH 3 , -NHCH 2 CH 3 , - NHCH 2 CH 2 CH 3 , -NHCH(CH 3 ) 2 , -N(CH 3 ) 2 , -N(CH 2 CH 3 ) 2 , -N(CH 2 CH 2 CH 3 ) 2 , and -N(CH(CH 3 ) 2 ) 2 , and carboxyl. Preferably, R 10 is hydrogen or deuterium.

[0043] A compound of Formula I-C, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, and an isotopic substitution thereof: wherein Q is O, S, SO, or SO 2 ; Z, R X1 , R X2 , R X3 , and m are the same as defined herein.

[0044] A compound of Formula II, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, and an isotopic substitution thereof: wherein Z, R X1 , R X2 , R X3 , and m are the same as defined herein.

[0045] In some embodiments of the compound of Formula I, I-A, I-B, I-C, or II, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, the compound is of Formula III: wherein R 1 , R X1 , R X2 , R X3 , and m are the same as defined herein.

[0046] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, or III, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, the compound is of Formula IV:

[0047] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, or IV, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, the compound is of Formula V:

[0048] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, or IV, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, the compound is of Formula VI:

[0049] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, or IV, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, the compound is of Formula VII:

[0050] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, or IV, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, the compound is of Formula VIII and a pharmaceutically acceptable salt thereof, a stereoisomer thereof,a tautomer thereof, an isotopic substitution thereof: wherein R 1 , R X1 , R X2 , R X3 , and m are the same as defined herein

[0051] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, or VIII, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein one or more hydrogen is optionally substitued with deuterium.

[0052] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, or VIII, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein one or more hydrogen in R1 or RX3 is substitued with deuterium, preferably, all hydrogens on one or more methyl groups, methylene groups, or methane groups are substituted with deuterium.

[0053] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, or VIII, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is selected from the group consisting of hydrogen, deuterium, hydrogen, deuterium, C 1-3 alkyl, C 1-3 alkoxy, and each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, CN, OH, C 1-4 alkyl, C 1-3 alkoxy, each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-6 alkyl), -N(C 1-3 alkyl) 2 , -S-C 1-3 alkyl; or R X3 is independently selected from the group consisting of hydrogen, deuterium, C 1-3 alkyl, C 1-3 alkoxy, each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, -C 1-3 alkyl, -C 1-3 alkoxy, -C 3-6 cycloalkyl, -NH 2 , -NH(C 1-3 alkyl), -N(C 1-3 alkyl) 2 , carboxy, -S- C 1-3 alkyl.

[0054] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, or VIII, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is selected from the group consisting of hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy; and each of which can be optional substituted with one or more substituents, which are independently selected from the group consisting of deuterium, F, Cl, Br, I, -OH, oxo, -CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy; R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, CN, CF 3 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butyl, sec-butyl, iso-butyl, tert-butyl, and each of which is independently optionally subsitituted with deuterium, -F, -Cl, - Br, -I, -NH 2 , -CN, -OH, oxo, carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy; or R X3 is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, tert-butyl, each of which can be substituted with deuterium.

[0055] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, or VIII, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is seleted from hydrogen, deuterium, isopropyl, methyl, ethyl, -tert-butyl, isopentyl, -CD 3 , -CH 2 CD 3 , -CD 2 CD 3 , -CD(CD 3 ) 2 , -CH(CD 3 ) 2 , R X1 and R X2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, CN, OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butyl, sec-butyl, iso-butyl, tert-butyl, R X3 is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, tert-butyl, -CD 3 , -CH 2 CD 3 , -CD 2 CD 3 .

[0056] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, or VIII, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention, wherein R 1 is selected from -CD 3 , -CH 2 CD 3 , -CD 2 CD 3 , - CD(CD 3 ) 2 , -CH(CD 3 ) 2 , the deuterated R X3 is selected from -CD 3 , -CH 2 CD 3 , -CD 2 CD 3

[0057] In some embodiments of the compound of Formula I, I-A, I-B, I-C, II, III, IV, V, VI, VII, or VIII, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present disclosure, wherein the compound is selected from: 1isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate2isopropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(7-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate4isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate5isopropyl (S)-6-diazo-2-(2-methoxyacetamido)-5-oxohexanoate6isopropyl (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate7isopropyl (S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate8isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-phenylpropanamido)-5-oxohexanoate9isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-phenylpropanamido)-5-oxohexanoate10isopropyl (S)-6-diazo-2-((S)-2-hydroxy-4-methylpentanamido)-5-oxohexanoate11isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-phenylacetamido)-5-oxohexanoate12isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-phenylacetamido)-5-oxohexanoate13isopropyl (S)-2-((S)-2-(2-cyanoacetoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate14isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(pivaloyloxy)propanamido)-6-diazo-5-oxohexanoate15isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-1-yl)propanamido)-5-oxohexanoate16isopropyl (S)-6-diazo-2-((S)-2-(4-fluorophenyl)-2-hydroxyacetamido)-5-oxohexanoate17isopropyl (S)-6-diazo-2-(2-((4-fluorobenzyl)oxy)acetamido)-5-oxohexanoate18isopropyl (S)-2-((S)-3-(7-cyano-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate19isopropyl (S)-2-((S)-3-(6-cyano-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate20isopropyl (S)-2-((S)-3-(5-cyano-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate21isopropyl (S)-2-((S)-3-(4-cyano-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate22isopropyl (S)-2-((S)-3-(7-cyano-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-5-oxohexanoate23isopropyl (S)-2-((S)-3-(6-cyano-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-5-oxohexanoate24isopropyl (S)-2-((S)-3-(5-cyano-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-5-oxohexanoate25isopropyl (S)-2-((S)-3-(4-cyano-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-5-oxohexanoate26isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(6-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate27isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(5-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate28isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(4-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate29isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(6-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate30isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(5-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate31isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(4-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate32isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(7-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate33isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1-methyl-1H-imidazol-4-yl)propanamido)-5-oxohexanoate34isopropyl (2S)-6-diazo-2-(2-hydroxy-3-(1H-indol-3-yl)-2-methylpropanamido)-5-oxohexanoate35isopropyl (S)-6-diazo-2-((S)-3-(6-fluoro-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate36isopropyl (S)-6-diazo-2-((S)-3-(5-fluoro-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate37isopropyl (S)-6-diazo-2-((S)-3-(4-fluoro-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate38isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate39isopropyl (S)-6-diazo-2-((S)-3-(6-fluoro-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate40isopropyl (S)-6-diazo-2-((S)-3-(5-fluoro-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate41isopropyl (S)-6-diazo-2-((S)-3-(4-fluoro-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate42isopropyl (S)-2-((S)-3-(7-chloro-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate43isopropyl (S)-2-((S)-3-(6-chloro-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate44isopropyl (S)-2-((S)-3-(5-chloro-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate45isopropyl (S)-2-((S)-3-(4-chloro-1H-indol-3-yl)-2-hydroxypropanamido)-6-diazo-5-oxohexanoate46isopropyl (S)-2-((S)-3-(7-chloro-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-3-oxohexanoate47isopropyl (S)-2-((S)-3-(6-chloro-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-5-oxohexanoate48isopropyl (S)-2-((S)-3-(5-chloro-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-3-oxohexanoate49isopropyl (S)-2-((S)-3-(4-chloro-1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-3-oxohexanoate50isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(7-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate51isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(6-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate52isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(5-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate53isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(4-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate54isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(7-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate55isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(6-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate56isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(5-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate57isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(4-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate58isopropyl (S)-6-diazo-2-((S)-3-(7-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate59isopropyl (S)-6-diazo-2-((S)-3-(6-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate60isopropyl (S)-6-diazo-2-((S)-3-(5-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate61isopropyl (S)-6-diazo-2-((S)-3-(4-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate62isopropyl (S)-6-diazo-2-((S)-3-(7-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate63isopropyl (S)-6-diazo-2-((S)-3-(6-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate64isopropyl (S)-6-diazo-2-((S)-3-(5-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate65isopropyl (S)-6-diazo-2-((S)-3-(4-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanamido)-5-oxohexanoate66S-isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanethioate67isopropyl (S)-6-diazo-2-((S)-2-ethoxypropanamido)-5-oxohexanoate68isopropyl (S)-6-diazo-2-((S)-2-isopropoxypropanamido)-5-oxohexanoate69isopropyl (S)-2-((S)-2-cyclopropoxypropanamido)-6-diazo-5-oxohexanoate70isopropyl (S)-6-diazo-2-(2-hydroxyacetamido)-5-oxohexanoate71isopropyl (5)-2-(2-cyclopropoxyacetamido)-6-diazo-5-oxohexanoate72isopropyl (S)-6-diazo-2-((S)-2-hydroxybutanamido)-5-oxohexanoate73isopropyl (S)-6-diazo-2-((S)-2-methoxybutanamido)-5-oxohexanoate74isopropyl (S)-6-diazo-2-((S)-2-ethoxybutanamido)-5-oxohexanoate75isopropyl (S)-6-diazo-2-((S)-2-isopropoxybutanamido)-5-oxohexanoate76isopropyl (S)-2-((S)-2-cyclopropoxybutanamido)-6-diazo-5-oxohexanoate77isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate78isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-methylbutanamido)-5-oxohexanoate79isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-methylbutanamido)-5-oxohexanoate80isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3-methylbutanamido)-5-oxohexanoate81isopropyl (S)-2-((S)-2-cyclopropoxy-3-methylbutanamido)-6-diazo-5-oxohexanoate82isopropyl (S)-6-diazo-2-((2S,3R)-2-hydroxy-3-methylpentanamido)-5-oxohexanoate83isopropyl (S)-6-diazo-2-((2S,3R)-2-methoxy-3-methylpentanamido)-5-oxohexanoate84isopropyl (S)-6-diazo-2-((2S,3R)-2-ethoxy-3-methylpentanamido)-5-oxohexanoate85isopropyl (S)-6-diazo-2-((2S,3R)-2-isopropoxy-3-methylpentanamido)-5-oxohexanoate86isopropyl (S)-2-((2S,3R)-2-cyclopropoxy-3-methylpentanamido)-6-diazo-5-oxohexanoate87isopropyl (S)-6-diazo-2-((S)-2-hydroxypentanamido)-5-oxohexanoate88isopropyl (S)-6-diazo-2-((S)-2-methoxypentanamido)-5-oxohexanoate89isopropyl (S)-6-diazo-2-((S)-2-ethoxypentanamido)-5-oxohexanoate90isopropyl (S)-6-diazo-2-((S)-2-isopropoxypentanamido)-5-oxohexanoate91isopropyl (S)-2-((S)-2-cyclopropoxypentanamido)-6-diazo-5-oxohexanoate92isopropyl (S)-6-diazo-2-((S)-2-methoxy-4-methylpentanamido)-5-oxohexanoate93isopropyl (S)-6-diazo-2-((S)-2-ethoxy-4-methylpentanamido)-5-oxohexanoate94isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-4-methylpentanamido)-5-oxohexanoate95isopropyl (S)-2-((S)-2-cyclopropoxy-4-methylpentanamido)-6-diazo-5-oxohexanoate96isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3,3-dimethylbutanamido)-5-oxohexanoate97isopropyl (S)-6-diazo-2-((S)-2-methoxy-3,3-dimethylbutanamido)-5-oxohexanoate98isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3,3-dimethylbutanamido)-5-oxohexanoate99isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3,3-dimethylbutanamido)-5-oxohexanoate100isopropyl (S)-2-((S)-2-cyclopropoxy-3,3-dimethylbutanamido)-6-diazo-5-oxohexanoate101isopropyl (S)-6-diazo-2-((S)-2-hydroxyhexanamido)-5-oxohexanoate102isopropyl (S)-6-diazo-2-((S)-2-methoxyhexanamido)-5-oxohexanoate103isopropyl (S)-6-diazo-2-((S)-2-ethoxyhexanamido)-5-oxohexanoate104isopropyl (S)-6-diazo-2-((S)-2-isopropoxyhexanamido)-5-oxohexanoate105isopropyl (S)-2-((S)-2-cyclopropoxyhexanamido)-6-diazo-5-oxohexanoate106isopropyl (S)-2-((S)-2-cyclopentyl-2-hydroxyacetamido)-6-diazo-5-oxohexanoate107isopropyl (S)-2-((S)-2-cyclopentyl-2-methoxyacetamido)-6-diazo-5-oxohexanoate108isopropyl (S)-2-((S)-2-cyclopentyl-2-ethoxyacetamido)-6-diazo-5-oxohexanoate109isopropyl (S)-2-((S)-2-cyclopentyl-2-isopropoxyacetamido)-6-diazo-5-oxohexanoate110isopropyl (S)-2-((S)-2-cyclopentyl-2-cyclopropoxyacetamido)-6-diazo-5-oxohexanoate111isopropyl (S)-2-((S)-3-cyclopentyl-2-hydroxypropanamido)-6-diazo-5-oxohexanoate112isopropyl (S)-2-((S)-3-cyclopentyl-2-methoxypropanamido)-6-diazo-5-oxohexanoate113isopropyl (S)-2-((S)-3-cyclopentyl-2-ethoxypropanamido)-6-diazo-5-oxohexanoate114isopropyl (S)-2-((S)-3-cyclopentyl-2-isopropoxypropanamido)-6-diazo-5-oxohexanoate115isopropyl (S)-2-((S)-3-cyclopentyl-2-cyclopropoxypropanamido)-6-diazo-5-oxohexanoate116isopropyl (S)-2-((S)-2-cyclohexyl-2-hydroxyacetamido)-6-diazo-5-oxohexanoate117isopropyl (S)-2-((S)-2-cyclohexyl-2-methoxyacetamido)-6-diazo-5-oxohexanoate118isopropyl (S)-2-((S)-2-cyclohexyl-2-ethoxyacetamido)-6-diazo-5-oxohexanoate119isopropyl (S)-2-((S)-2-cyclohexyl-2-isopropoxyacetamido)-6-diazo-5-oxohexanoate120isopropyl (S)-2-((S)-2-cyclohexyl-2-cyclopropoxyacetamido)-6-diazo-5-oxohexanoate121isopropyl (S)-6-diazo-2-((S)-2-ethoxy-2-phenylacetamido)-5-oxohexanoate122isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-2-phenylacetamido)-5-oxohexanoate123isopropyl (S)-2-((S)-2-cyclopropoxy-2-phenylacetamido)-6-diazo-5-oxohexanoate124isopropyl (S)-6-diazo-2-((S)-2-(4-fluorophenyl)-2-methoxyacetamido)-5-oxohexanoate125isopropyl (S)-2-((S)-2-(4-chlorophenyl)-2-methoxyacetamido)-6-diazo-5-oxohexanoate126isopropyl (S)-2-((S)-2-(4-chlorophenyl)-2-hydroxyacetamido)-6-diazo-5-oxohexanoate127isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(4-methoxyphenyl)acetamido)-5-oxohexanoate128isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(4-methoxyphenyl)acetamido)-5-oxohexanoate129isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(4-hydroxyphenyl)acetamido)-5-oxohexanoate130isopropyl (S)-6-diazo-2-((S)-2-(4-hydroxyphenyl)-2-methoxyacetamido)-5-oxohexanoate131isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(p-tolyl)acetamido)-5-oxohexanoate132isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(p-tolyl)acetamido)-5-oxohexanoate133isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-phenylpropanamido)-5-oxohexanoate134isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3-phenylpropanamido)-5-oxohexanoate135isopropyl (S)-2-((S)-2-cyclopropoxy-3-phenylpropanamido)-6-diazo-5-oxohexanoate136isopropyl (5)-6-diazo-2-((S)-3-(4-fluorophenyl)-2-hydroxypropanamido)-3-oxohexanoate137isopropyl (S)-6-diazo-2-((S)-3-(4-fluorophenyl)-2-methoxypropanamido)-5-oxohexanoate138isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(4-fluorophenyl)propanamido)-5-oxohexanoate139isopropyl (S)-6-diazo-2-((S)-3-(4-fluorophenyl)-2-isopropoxypropanamido)-5-oxohexanoate140isopropyl (S)-2-((S)-2-cyclopropoxy-3-(4-fluorophenyl)propanamido)-6-diazo-5-oxohexanoate141isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(4-hydroxyphenyl)propanamido)-5-oxohexanoate142isopropyl (S)-6-diazo-2-((S)-3-(4-hydroxyphenyl)-2-methoxypropanamido)-5-oxohexanoate143isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(4-hydroxyphenyl)propanamido)-5-oxohexanoate144isopropyl (S)-6-diazo-2-((S)-3-(4-hydroxyphenyl)-2-isopropoxypropanamido)-5-oxohexanoate145isopropyl (S)-2-((S)-2-cyclopropoxy-3-(4-hydroxyphenyl)propanamido)-6-diazo-5-oxohexanoate146isopropyl (S)-6-diazo-2-(1-hydroxycyclobutane-1-carboxamido)-5-oxohexanoate147isopropyl (S)-6-diazo-2-(1-methoxycyclobutane-1-carboxamido)-5-oxohexanoate148isopropyl (S)-6-diazo-2-(3-hydroxyoxetane-3-carboxamido)-5-oxohexanoate149isopropyl (S)-6-diazo-2-(3-methoxyoxetane-3-carboxamido)-5-oxohexanoate150isopropyl (S)-6-diazo-2-(1-hydroxycyclopentane-1-carboxamido)-5-oxohexanoate151isopropyl (S)-6-diazo-2-(1-methoxycyclopentane-1-carboxamido)-5-oxohexanoate152isopropyl (2S)-6-diazo-2-(3-hydroxytetrahydrofuran-3-carboxamido)-5-oxohexanoate153isopropyl (2S)-6-diazo-2-(3-methoxytetrahydrofuran-3-carboxamido)-5-oxohexanoate154isopropyl (S)-6-diazo-2-(1-hydroxycyclohexane-1-carboxamido)-5-oxohexanoate155isopropyl (S)-6-diazo-2-(1-methoxycyclohexane-1-carboxamido)-5-oxohexanoate156isopropyl (S)-6-diazo-2-(4-hydroxy-1-methylpiperidine-4-carboxamido)-5-oxohexanoate157isopropyl (S)-6-diazo-2-(4-methoxy-1-methylpiperidine-4-carboxamido)-5-oxohexanoate158isopropyl (2S)-6-diazo-5-oxo-2-(tetrahydrofuran-2-carboxamido)hexanoate159isopropyl (2S)-6-diazo-5-oxo-2-(tetrahydro-2H-pyran-2-carboxamido)hexanoate or160isopropyl (2S)-6-diazo-2-(hexahydro-1H-cyclopenta[c]furan-1-carboxamido)-5-oxohexanoate.161isopropyl (S)-2-(2-(cyclopropylmethoxy)acetamido)-6-diazo-5-oxohexanoate162isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-phenylpropanamido)-5-oxohexanoate163isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-phenylpropanamido)-5-oxohexanoate164isopropyl (S)-2-((S)-2-(2-cyanoacetoxy)-3-(7-fluoro-1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate165isopropyl (S)-2-((S)-2-acetoxy-3-(7-fluoro-1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate166isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-(isobutyryloxy)propanamido)-5-oxohexanoate167(S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoic acid168methyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate1691-methylpiperidin-4-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate170isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydrofuran-2-carboxamido)hexanoate171isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydro-2H-pyran-2-carboxamido)hexanoate172isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydrofuran-3-carboxamido)hexanoate173isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydro-2H-pyran-3-carboxamido)hexanoate174isopropyl (S)-6-diazo-2-(3-methoxy-2-oxopropanamido)-5-oxohexanoate175isopropyl (S)-6-diazo-2-(3-hydroxy-2-oxopropanamido)-5-oxohexanoate176ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate177cyclopropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate178cyclobutyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate179cyclopentyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate1802-(pyrrolidin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate181(pivaloyloxy)methyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate182isopentyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate183isopropyl (S)-6-diazo-2-(3-hydroxypropanamido)-5-oxohexanoate184isopropyl (S)-6-diazo-2-((S)-3-hydroxybutanamido)-5-oxohexanoate185isopropyl (S)-6-diazo-2-(3-methoxypropanamido)-5-oxohexanoate186isopropyl (S)-6-diazo-2-((S)-3-methoxybutanamido)-5-oxohexanoate187isopropyl (S)-6-diazo-2-((S)-3-hydroxy-2-methylpropanamido)-5-oxohexanoate188isopropyl (S)-6-diazo-2-((S)-3-methoxy-2-methylpropanamido)-5-oxohexanoate189isopropyl (S)-6-diazo-2-((S)-oxetane-2-carboxamido)-5-oxohexanoate190isopropyl (S)-6-diazo-2-((2S,3R)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate191isopropyl (S)-6-diazo-2-((2S,3R)-3-metlioxy-2-methylbutanamido)-5-oxohexanoate192isopropyl (S)-6-diazo-2-((2R,3R)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate193isopropyl (S)-6-diazo-2-((2R,3R)-3-methoxy-2-methylbutanamido)-5-oxohexanoate194isopropyl (S)-6-diazo-2-((2R,3S)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate195isopropyl (S)-6-diazo-2-((2R,3S)-3-methoxy-2-methylbutanamido)-5-oxohexanoate196isopropyl (S)-6-diazo-2-((R)-3-hydroxybutanamido)-5-oxohexanoate197isopropyl (S)-6-diazo-2-((2S,3S)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate198isopropyl (S)-6-diazo-2-((2S,3S)-3-methoxy-2-methylbutanamido)-5-oxohexanoate199isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydrofuran-2-carboxamido)hexanoate200isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydro-2H-pyran-2-carboxamido)hexanoate201isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydrofuran-3-carboxamido)hexanoate202isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydro-2H-pyran-3-carboxamido)hexanoate203isopropyl (S)-6-diazo-2-((R)-3-methoxybutanamido)-5-oxohexanoate204isopropyl (S)-6-diazo-5-oxo-2-((R)-3,3,3-trifluoro-2-methoxypropanamido)hexanoate205isopropyl (S)-6-diazo-5-oxo-2-((R)-3,3,3-trifluoro-2-hydroxypropanamido)hexanoate206isopropyl (S)-6-diazo-5-oxo-2-((S)-3,3,3-trifluoro-2-methoxypropanamido)hexanoate207isopropyl (S)-6-diazo-5-oxo-2-((S)-3,3,3-trifluoro-2-hydroxypropanamido)hexanoate208isopropyl (S)-6-diazo-2-((R)-oxetane-2-carboxamido)-5-oxohexanoate209isopropyl (S)-6-diazo-2-(oxetane-3-carboxamido)-5-oxohexanoate210isopropyl (S)-6-diazo-2-((R)-3-hydroxy-2-methylpropanamido)-5-oxohexanoate211isopropyl (S)-6-diazo-5-oxo-2-(tetrahydro-2H-pyran-4-carboxamido)hexanoate212isopropyl (2S)-6-diazo-5-oxo-2-((1S)-tetrahydro-1H,3H-furo[3,4-c]furan-1-carboxamido)hexanoate213isopropyl (2S)-6-diazo-5-oxo-2-((1R)-tetrahydro-1H,3H-furo[3,4-c]furan-1-carboxamido)hexanoate214isopropyl (S)-2-((S)-2-cyano-2-hydroxyacetamido)-6-diazo-5-oxohexanoate215isopropyl (S)-2-((S)-2-cyano-2-methoxyacetamido)-6-diazo-5-oxohexanoate216isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-oxobutanamido)-5-oxohexanoate217isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-oxobutanamido)-5-oxohexanoate218isopropyl (S)-6-diazo-2-((R)-3-methoxy-2-methylpropanamido)-5-oxohexanoate219isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate220isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate221isopropyl (S)-2-((R)-2-cyano-2-hydroxyacetamido)-6-diazo-5-oxohexanoate222isopropyl (S)-2-((R)-2-cyano-2-methoxyacetamido)-6-diazo-5-oxohexanoate223isopropyl (S)-6-diazo-2-((R)-2-methoxy-3-oxobutanamido)-5-oxohexanoate224isopropyl (S)-6-diazo-2-((R)-2-hydroxy-3-oxobutanamido)-5-oxohexanoate225isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate226isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate227isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate228isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate229isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate230isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate231isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate232isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate233isopropyl (S)-6-diazo-2-((S)-2-(furan-2-yl)-2-methoxyacetamido)-5-oxohexanoate234isopropyl (S)-6-diazo-2-((S)-2-(furan-3-yl)-2-methoxyacetamido)-5-oxohexanoate235isopropyl (S)-6-diazo-2-((S)-2-(furan-2-yl)-2-hydroxyacetamido)-5-oxohexanoate236isopropyl (S)-6-diazo-2-((S)-2-(furan-3-yl)-2-hydroxyacetamido)-5-oxohexanoate237isopropyl (S)-2-((S)-2-(1H-imidazol-4-yl)-2-methoxyacetamido)-6-diazo-5-oxohexanoate238isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-imidazol-4-yl)acetamido)-5-oxohexanoate239isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate240isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate241isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate242isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate243isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate244isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate245isopropyl (S)-6-diazo-2-((R)-2-(furan-2-yl)-2-methoxyacetamido)-5-oxohexanoate246isopropyl (S)-6-diazo-2-((R)-2-(furan-3-yl)-2-methoxyacetamido)-5-oxohexanoate247isopropyl (S)-6-diazo-2-((R)-2-(furan-2-yl)-2-hydroxyacetamido)-5-oxohexanoate248isopropyl (S)-6-diazo-2-((R)-2-(furan-3-yl)-2-hydroxyacetamido)-5-oxohexanoate249isopropyl (S)-2-((R)-2-(1H-imidazol-4-yl)-2-methoxyacetamido)-6-diazo-5-oxohexanoate250isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-imidazol-4-yl)acetamido)-5-oxohexanoate251isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate252isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate253isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate254isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate255isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate256isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate257isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-5-oxohexanoate258isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-5-oxohexanoate259isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate260isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate261isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate262isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate263isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate264isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate265isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate266isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate267isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate268isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate269isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate270isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate271isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate272isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate273isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-5-oxohexanoate274isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-3-oxohexanoate275isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiazol-5-yl)acetamido)-5-oxohexanoate276isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiazol-5-yl)acetamido)-5-oxohexanoate277isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1-methyl-1H-imidazol-5-yl)acetamido)-5-oxohexanoate278isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1-methyl-1H-imidazol-5-yl)acetamido)-5-oxohexanoate279isopropyl (S)-2-((R)-2-(1H-imidazol-2-yl)-2-methoxyacetamido)-6-diazo-5-oxohexanoate280isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-imidazol-2-yl)acetamido)-5-oxohexanoate281isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(oxazol-5-yl)acetamido)-5-oxohexanoate282isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(oxazol-5-yl)acetamido)-5-oxohexanoate283isopropyl (S)-2-((S)-2-(1H-imidazol-5-yl)-2-methoxyacetamido)-6-diazo-5-oxohexanoate284isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-imidazol-5-yl)acetamido)-5-oxohexanoate285isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate286isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate287isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate288isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate289isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate290isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate291isopropyl (S)-6-diazo-2-((S)-2-(3-fluoropyridin-4-yl)-2-methoxyacetamido)-5-oxohexanoate292isopropyl (S)-6-diazo-2-((S)-2-(3-fluoropyridin-4-yl)-2-hydroxyacetamido)-5-oxohexanoate293isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-2-yl)-2-methoxyacetamido)-5-oxohexanoate294isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-2-yl)-2-hydroxyacetamido)-5-oxohexanoate295isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-3-yl)-2-methoxyacetamido)-5-oxohexanoate296isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-3-yl)-2-hydroxyacetamido)-5-oxohexanoate297isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(3-methoxypyridin-4-yl)acetamido)-3-oxohexanoate298isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(3-methoxypyridin-4-yl)acetamido)-5-oxohexanoate299isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(5-methoxypyridin-2-yl)acetamido)-3-oxohexanoate300isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(5-methoxypyridin-2-yl)acetamido)-5-oxohexanoate301isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(5-methoxypyridin-3-yl)acetamido)-3-oxohexanoate302isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(5-methoxypyridin-3-yl)acetamido)-3-oxohexanoate303isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(5-methoxypyridin-2-yl)acetamido)-5-oxohexanoate304isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(5-methoxypyridin-2-yl)acetamido)-3-oxohexanoate305isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(5-methoxypyridin-3-yl)acetamido)-5-oxohexanoate306isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(5-methoxypyridin-3-yl)acetamido)-3-oxohexanoate307isopropyl (S)-2-((R)-2-(1H-imidazol-5-yl)-2-methoxyacetamido)-6-diazo-5-oxohexanoate308isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-imidazol-5-yl)acetamido)-5-oxohexanoate309isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate310isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate311isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate312isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate313isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate314isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate315isopropyl (S)-6-diazo-2-((R)-2-(3-fluoropyridin-4-yl)-2-methoxyacetamido)-5-oxohexanoate316isopropyl (S)-6-diazo-2-((R)-2-(3-fluoropyridin-4-yl)-2-hydroxyacetamido)-5-oxohexanoate317isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-2-yl)-2-methoxyacetamido)-5-oxohexanoate318isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-2-yl)-2-hydroxyacetamido)-5-oxohexanoate319isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-3-yl)-2-methoxyacetamido)-5-oxohexanoate320isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-3-yl)-2-hydroxyacetamido)-5-oxohexanoate321isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(3-methoxypyridin-4-yl)acetamido)-5-oxohexanoate322isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(3-methoxypyridin-4-yl)acetamido)-3-oxohexanoate323tert-butyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate324phenyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate325benzyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate326cyclohexyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate327cycloheptyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate328cyclooctyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate329cyclooctyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate330tert-butyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate331phenyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate332benzyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate333cyclohexyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate334cycloheptyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3351-methylpiperidin-4-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate336pyridin-4-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate337pyridin-4-ylmethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate338tetrahydro-2H-pyran-4-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate339piperidin-4-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate340(R)-oxepan-4-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate341(S)-oxepan-4-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate342oxocan-5-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate343pyridin-4-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate344pyridin-4-ylmethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate345tetrahydro-2H-pyran-4-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate346piperidin-4-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate347(R)-oxepan-4-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate348(S)-oxepan-4-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate349oxocan-5-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate350trifluoromethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3512,2,2-trifluoroethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate352(S)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3533,3,3-trifluoropropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate354(S)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3551,1,1-trifluoro-2-methylpropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3564,4,4-trifluoro-2-methylbutan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate357cyanic (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoic anhydride358cyanomethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate359(S)-1-cyanoethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3602-cyanoethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3611-cyanopropan-2-yl (2S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3622-cyanopropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3631-cyano-2-methylpropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate364hydroxymethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate365methoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate366ethoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate367isopropoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate368cyclopropoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate369cyclobutoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate370trifluoromethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3712,2,2-trifluoroethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate372(S)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate373(R)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate374(R)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate375(R)-1-cyanoethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate376(R)-1-cyanopropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate377(R)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3783,3,3-trifluoropropyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate379(S)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate380(R)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3811,1,1-trifluoro-2-methylpropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3824,4,4-trifluoro-2-methylbutan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate383cyanic (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoic anhydride384cyanomethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate385(S)-1-cyanoethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate386(R)-1-cyanoethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3872-cyanoethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate388(S)-1-cyanopropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate389(R)-1-cyanopropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3902-cyanopropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3911-cyano-2-methylpropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate392hydroxymethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate393methoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate394ethoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate395isopropoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate396cyclopropoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate397cyclobutoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3982-(pyrrolidin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate3992-methoxyethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4002-ethoxyethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4012-isopropoxyethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4022-aminoethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4032-(methylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4042-(dimethylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4052-(ethylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4062-(isopropylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4072-(cyclopropylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4082-(cyclobutylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4092-(cyclopentylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4102-(cyclohexylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4112-(azetidin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4122-(piperidin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4132-(azepan-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4142-(azocan-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4152-morpholinoethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4162-(phenylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4172-(pyridin-4-ylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4182-(benzylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4192-((pyridin-4-ylmethyl)amino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4202-(4-methylpiperazin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4212-methoxyethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4222-ethoxyethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4232-isopropoxyethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4242-aminoethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4252-(methylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4262-(dimethylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4272-(ethylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4282-(isopropylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4292-(cyclopropylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4302-(cyclobutylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4312-(cyclopentylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4322-(cyclohexylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4332-(azetidin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4342-(piperidin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4352-(azepan-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4362-(azocan-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4372-morpholinoethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4382-(phenylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4392-(pyridin-4-ylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4402-(benzylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4412-((pyridin-4-ylmethyl)amino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate4422-(4-methylpiperazin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate443isopropyl (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate444isopropyl (S)-6-diazo-2-(2-hydroxy-2-methylpropanamido)-5-oxohexanoate445methyl (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate446methyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate447methyl (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate448methyl (S)-6-diazo-2-(2-isopropoxyacetamido)-5-oxohexanoate449(S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoic acid450isopropyl (S)-2-((S)-2-acetoxy-3-(1H-indol-3-yl)propanatnido)-6-diazo-5-oxohexanoate451isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-methoxypropanamido)-6-diazo-5-oxohexanoate452isopropyl (S)-6-diazo-2-(2-isopropoxyacetamido)-5-oxohexanoate453isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate454isopropyl (S)-6-diazo-2-((R)-2-methoxy-3-(1-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate455isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate456methyl (S)-6-diazo-2-((S)-2-hydroxy-2-phenylacetamido)-5-oxohexanoate457methyl (S)-6-diazo-2-((S)-2-methoxy-2-phenylacetamido)-5-oxohexanoate458methyl (S)-6-diazo-2-(2-methoxyacetamido)-5-oxohexanoate459S-isopropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate460(S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoic acid461isopropyl (2S)-2-(2-acetoxy-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate462isopropyl (2S)-2-(2-(2-cyanoacetoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate463isopropyl (2S)-6-diazo-2-(2-((dimethylglycyl)oxy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate464isopropyl (2S)-2-(3-(1H-indol-3-yl)-2-(2-(2-oxopyrrolidin-1-yl)acetoxy)propanamido)-6-diazo-5-oxohexanoate465isopropyl (2S)-6-diazo-2-(2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate466isopropyl (S)-6-diazo-2-((S)-2-(2-hydroxyethoxy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate467isopropyl (S)-2-((S)-2-(2-acetamidoethoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate468isopropyl (S)-2-((S)-2-(2-cyanoethoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate469isopropyl (S)-2-((S)-2-(cyanomethoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate470isopropyl (S)-6-diazo-2-((S)-2-(2-(dimethylamino)-2-oxoethoxy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate471isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(2-(methylamino)-2-oxoethoxy)propanamido)-6-diazo-5-oxohexanoate472isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(2-oxopropoxy)propanamido)-6-diazo-5-oxohexanoate473isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-((tetrahydro-2H-pyran-4-yl)oxy)propanamido)-6-diazo-5-oxohexanoate474isopropyl (S)-2-((S)-2-(3-amino-3-oxopropoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate475isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(3-(methylamino)-3-oxopropoxy)propanamido)-6-diazo-5-oxohexanoate476isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate477isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1H-pyrrolo[3,2-b]pyridin-3-yl)propanamido)-5-oxohexanoate478isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanamido)-5-oxohexanoate479isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)propanamido)-5-oxohexanoate480isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamido)-5-oxohexanoate481isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(7-fluoro-1H-indol-3-yl)propanamido)-5-oxohexanoate482isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-isopropoxypropanamido)-5-oxohexanoate483isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-phenoxypropanamido)-6-diazo-5-oxohexanoate484isopropyl (2S)-2-(3-(1H-indol-3-yl)-2-((methylglycyl)oxy)propanamido)-6-diazo-5-oxohexanoate485isopropyl (2S)-6-diazo-2-(2-(glycyloxy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate486isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate487(S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoic acid488methyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate489ethyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate490S-isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate491isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoate492methyl-d3 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate493ethyl-2,2,2-d3 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate494isopropyl (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate495isopropyl (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate496ethyl-d5 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate497propan-2-yl-d7 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate498propan-2-yl-d7 (S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate499propan-2-yl-d7 (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate500propan-2-yl-d7 (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate501S-(propan-2-yl-d7) (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate502propan-2-yl-d7 (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate503methyl-d3 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate504ethyl-2,2,2-d3 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate505ethyl-d5 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate506propan-2-yl-d7 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate507propan-2-yl-d7 (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate508S-(propan-2-yl-d7) (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate509propan-2-yl-d7 (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoate510propan-2-yl-d7 (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate511methyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate-2-d512ethyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate-2-d513isopropyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate-2-d514isopropyl 6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate-2-d515S-isopropyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate-2-d516isopropyl 6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate-2-d517isopropyl 6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate-2-d518isopropyl 6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate-2-d519propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate520propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate521S-(propan-2-yl-1,1,1,3,3,3-d6) (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate522propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoate523propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate524propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate525propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate526propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate527propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate528S-(propan-2-yl-1,1,1-d3) (2S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate529propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoate530propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate531propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate532propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate533propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate534propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate535S-(propan-2-yl-1,1,1,3,3,3-d6) (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate536propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate537propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate538propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate539S-(propan-2-yl-1,1,1-d3) (2S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate540propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate541methyl (S)-6-diazo-2-((S)-2-(methylthio)propanamido)-5-oxohexanoate542ethyl (S)-6-diazo-2-((S)-2-(methylthio)propanamido)-5-oxohexanoate543isopropyl (S)-6-diazo-2-((S)-2-(methylthio)propanamido)-5-oxohexanoate544isopropyl (S)-6-diazo-2-((S)-2-mercaptopropanamido)-5-oxohexanoate545isopropyl (S)-6-diazo-2-((S)-2-mercapto-3-methylbutanamido)-5-oxohexanoate546isopropyl (S)-6-diazo-2-(2-(ethylthio)acetamido)-5-oxohexanoate547S-isopropyl (S)-6-diazo-2-((S)-2-(methylthio)propanamido)-5-oxohexanethioate548isopropyl (S)-2-((S)-2,4-bis(methylthio)butanamido)-6-diazo-5-oxohexanoate549isopropyl (S)-6-diazo-2-((S)-2-(ethylthio)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate550isopropyl (S)-2-((S)-2-(acetylthio)-4-(methylthio)butanamido)-6-diazo-5-oxohexanoate551isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(methylthio)propanamido)-6-diazo-5-oxohexanoate552isopropyl (S)-6-diazo-2-(2-(isopropylthio)acetamido)-5-oxohexanoate553isopropyl (S)-6-diazo-2-((S)-2-(methylthio)-3-phenylpropanamido)-5-oxohexanoate554isopropyl (S)-6-diazo-2-((S)-2-(methylthio)-2-phenylacetamido)-5-oxohexanoate555isopropyl (S)-6-diazo-2-((S)-2-(methylthio)butanamido)-5-oxohexanoate556isopropyl (S)-6-diazo-2-((S)-3-methyl-2-(methylthio)butanamido)-5-oxohexanoate557cyclopentyl (S)-6-diazo-2-((S)-2-(methylthio)propanamido)-5-oxohexanoate558isopropyl (S)-6-diazo-5-oxo-2-((S)-thietane-2-carboxamido)hexanoate559methyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)propanamido)-5-oxohexanoate560ethyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)propanamido)-5-oxohexanoate561isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)propanamido)-5-oxohexanoate562isopropyl (2S)-6-diazo-2-(2-(ethylsulfinyl)acetamido)-5-oxohexanoate563S-isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)propanamido)-5-oxohexanethioate564isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)-4-(methylthio)butanamido)-5-oxohexanoate565isopropyl (2S)-6-diazo-2-((2S)-2-(ethylsulfinyl)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate566isopropyl (2S)-2-((2S)-3-(1H-indol-3-yl)-2-(methylsulfinyl)propanamido)-6-diazo-5-oxohexanoate567isopropyl (2S)-6-diazo-2-(2-(isopropylsulfinyl)acetamido)-5-oxohexanoate568isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)-3-phenylpropanamido)-5-oxohexanoate569isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)-2-phenylacetamido)-5-oxohexanoate570isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)butanamido)-5-oxohexanoate571isopropyl (2S)-6-diazo-2-((2S)-3-methyl-2-(methylsulfinyl)butanamido)-5-oxohexanoate572cyclopentyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)propanamido)-5-oxohexanoate573methyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)propanamido)-5-oxohexanoate574ethyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)propanamido)-5-oxohexanoate575isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)propanamido)-5-oxohexanoate576isopropyl (S)-6-diazo-2-(2-(ethylsulfonyl)acetamido)-5-oxohexanoate577S-isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)propanamido)-5-oxohexanethioate578isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)-4-(methylthio)butanamido)-5-oxohexanoate579isopropyl (S)-6-diazo-2-((S)-2-(ethylsulfonyl)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate580isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(methylsulfonyl)propanamido)-6-diazo-5-oxohexanoate581isopropyl (S)-6-diazo-2-(2-(isopropylsulfonyl)acetamido)-5-oxohexanoate582isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)-3-phenylpropanamido)-5-oxohexanoate583isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)-2-phenylacetamido)-5-oxohexanoate584isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)butanamido)-5-oxohexanoate585isopropyl (S)-6-diazo-2-((S)-3-methyl-2-(methylsulfonyl)butanamido)-5-oxohexanoate586cyclopentyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)propanamido)-5-oxohexanoate

[0058] It is noted that all compounds in compounds 1-586 that are not encompassed by the wording of the claims are considered as useful for understanding the invention. Only the compounds covered by the claims are part of the invention.METHODS OF PREPRATION (embodiment useful for understanding the invention)

[0059] The compounds of the present invention can be prepared in a number ways well known to one skilled in the art of organic synthesis using the methods described below or variations thereon as appreciated by those skilled in the art.

[0060] The methods of synthesis described herein after are intended as an illustration of the invention, without restricting its subject matter and the scope of the compounds claimed to these examples. Where the preparation of starting compounds is not described, they are commercially obtainable or may be prepared analogously to known compounds or methods described herein. Compounds of any of the formulae desctribed herein may be synthesized by reference to methods illustrated in the following schemes. As shown herein, the end compound is a product having the same structural formula depicted as any of formulaes. It will be understood that any compound of the formulaes may be prepared by the suitable selection of reagents with appropriate substitution. Solvents, temperature, pressures, and other reaction conditions may be readily selected by one of ordinary skill in the art.

[0061] For illustrative purposes, Scheme 1 and Scheme 2 show general synthetic methods for preparing the compounds described herein. For a more detailed description of the individual reaction steps, see the Examples section below. Those skilled in the art will appreciate that other synthetic routes may be used to synthesize the compounds. In addition, many of the compounds prepared by the methods described below can be further modified in light of this disclosure using conventional chemistry well known those skilled in the art.

[0062] General routes to compounds illustrated in the invention is described in Scheme 1 and Scheme 2, where the Z, R X1 , R X2 , R X3 , and m etc. substituents are defined previously in the text or a functional group that can be converted to the desired final substituent.

[0063] As depicted in Scheme 1 and Scheme 2, condensation reaction of the acid i with the amine ii gives iii using orgnic base and condensation reagents. Hydrolysis reaction of iii can provide iv using LiOH, NaOH, etc. Under orgnic base and condensation reagents, condensation reaction between iv and alcohols or mercaptans gives iii as a different ester or thioester.

[0064] Wherein the orgnic base is preferably DIPEA, NMM, 1-Methylimidazole, 2,4,6-Collidine and so on. The condensation reagents is preferably HATU, TCFH, XtalFluor-E, N,N'-Diisopropylcarbodiimide and so on.

[0065] It will be appreciated that other synthetic routes may be available for practice of the present invention.

[0066] In another aspect, provided here is a pharmaceutical composition comprising the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention; and a pharmaceutically acceptable carrier, diluent or excipient.

[0067] In another aspect, provided here is a method for treating a disease or a condition, the method comprising administering to a subject in need of treatment of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof; or a pharmaceutical composition thereof, in an amount effective for treating the disease or condition. In still other aspects, the presently disclosed subject matter provides the use of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof, for treating a disease or condition. In some embodiments, the disease or condition is selected from the group consisting of an infection, cancer, an autoimmune disease, an inflammatory disease, and a neurodegenerative or neurological disease.

[0068] As used herein, a "cancer" in a patient refers to the presence of cells possessing characteristics typical of cancer-causing cells, for example, uncontrolled proliferation, loss of specialized functions, immortality, significant metastatic potential, significant increase in anti-apoptotic activity, rapid growth and proliferation rate, and certain characteristic morphology and cellular markers. In some circumstances, cancer cells will be in the form of a tumor; such cells may exist locally within an animal, or circulate in the blood stream as independent cells, for example, leukemic cells. A "tumor," as used herein, refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all precancerous and cancerous cells and tissues. A "solid tumor," as used herein, is an abnormal mass of tissue that generally does not contain cysts or liquid areas. A solid tumor may be in the brain, colon, breasts, prostate, liver, kidneys, lungs, esophagus, head and neck, ovaries, cervix, stomach, colon, rectum, bladder, uterus, testes, and pancreas, as non-limiting examples. In some embodiments, the solid tumor regresses or its growth is slowed or arrested after the solid tumor is treated with the presently disclosed methods. In other embodiments, the solid tumor is malignant. In some embodiments, the cancer comprises Stage 0 cancer. In some embodiments, the cancer comprises Stage I cancer. In some embodiments, the cancer comprises Stage II cancer. In some embodiments, the cancer comprises Stage III cancer. In some embodiments, the cancer comprises Stage IV cancer. In some embodiments, the cancer is refractory and / or metastatic. For example, the cancer may be refractory to treatment with radiotherapy, chemotherapy or monotreatment with immunotherapy. Cancer as used herein includes newly diagnosed or recurrent cancers, including without limitation, acute lymphoblastic leukemia, acute myelogenous leukemia, advanced soft tissue sarcoma, brain cancer, metastatic or aggressive breast cancer, breast carcinoma, bronchogenic carcinoma, choriocarcinoma, chronic myelocytic leukemia, colon carcinoma, colorectal carcinoma, Ewing's sarcoma, gastrointestinal tract carcinoma, glioma, glioblastoma multiforme, head and neck squamous cell carcinoma, hepatocellular carcinoma, Hodgkin's disease, intracranial ependymoblastoma, large bowel cancer, leukemia, liver cancer, lung carcinoma, Lewis lung carcinoma, lymphoma, malignant fibrous histiocytoma, a mammary tumor, melanoma, mesothelioma, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, a pontine tumor, premenopausal breast cancer, prostate cancer, rhabdomyosarcoma, reticulum cell sarcoma, sarcoma, small cell lung cancer, a solid tumor, stomach cancer, testicular cancer, and uterine carcinoma.

[0069] In yet another aspect, provided here is a method of treating a subject having a cancer, said method comprising administering to the subject a therapeutically effective amount of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention; or the pharmaceutical composition of the present invention.

[0070] In some embodiments, the cancer is selected from lung cancer, pancreatic cancer, liver cancer, breast cancer, colon cancer, leukemia, glioblastoma or head and neck cancer.

[0071] In another aspect, provided here is use of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention; or the pharmaceutical composition of the present invention for the manufacture of a medicament for the treatment of a cancer.

[0072] In some embodiments, the cancer is selected from lung cancer, pancreatic cancer, liver cancer, breast cancer, colon cancer, leukemia, glioblastoma or head and neck cancer.

[0073] In some embodiments, the medicament is used as a glutamine antagonist.

[0074] As used herein, the term "glutamine antagonist" refers to a glutamine analog that interfers with a glutamine metabolic pathway, e.g., the inhibition or blocking of a metabolic pathway downstream of glutamine in which glutamine acts as a precursor of one or more non-glutamine compounds. Examples of such metabolic pathways are well known (see, e.g., Hensley et al, "Glutamine and cancer: cell biology, physiology, and clinical opportunities" J Clin Invest. 2013; 123(9):3678-3684; DeBerardinis et al, "Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer" Oncogene. 2009; 29(3):313-324; and Medina et al, "Relevance of glutamine metabolism to tumor cell growth" Mol Cell Biochem. 1992; 113(1): 1 -15). In some contexts, the term glutamine antagonist also includes glutamine analogs that inhibit glutamine uptake by cells, thereby reducing its biological activity. Diseases or conditions wherein excess and / or aberrant glutamine.

[0075] In yet another aspect, provided here is the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention; or the pharmaceutical composition of the present invention for use in therapy.

[0076] In yet another aspect, provided here is the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention; or the pharmaceutical composition of the present invention for use as a medicament.

[0077] In yet another aspect, provided here is the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention; or the pharmaceutical composition of the present invention, for use in treating the disease or condition. In some embodiments, the disease or condition is selected from the group consisting of an infection, cancer, an autoimmune disease, an inflammatory disease, and a neurodegenerative or neurological disease.

[0078] In yet another aspect, provided here is the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof of the present invention; or the pharmaceutical composition of the present invention for use in the treatment of a cancer.

[0079] In some embodiments, the cancer is selected from lung cancer, pancreatic cancer, liver cancer, breast cancer, colon cancer, leukemia, glioblastoma or head and neck cancer.

[0080] The compounds provided herein used as active ingredient, are characterized by improved solubility, improved stability, improved safety, improved pKa properties, and high pharmacokinetics.Brief description of the Drawings

[0081] Figure 1 shows the plasma stability of compounds after incubation for 4 hours in the presence of dog, monkey, swine and human plasma. Figure 2 shows the body weight changes following administration of Reference compound A and Compound 2 in C57BL / 6 mice bearing MC38 tumors. Figure 3 shows the anti-tumor efficacy of Reference compound A and Compound 2 in C57BL / 6 mice bearing MC38 tumors. Figure 4 shows the body weight changes following administration of Reference compound A and Compound 2 in CES1- / - mice bearing MC38 tumors.. Figure 5 shows the anti-tumor efficacy of Reference compound A and Compound 2 in CES1- / - mice bearing MC38 tumors. Figure 6 shows the body weight changes following administration of Compound 2, compound 3, compound 81, compound 443 and compound 459 in C57BL / 6 mice bearing MC38 tumors. Figure 7 shows the anti-tumor efficacy of Compound 2, compound 3, compound 81, compound 443 and compound 459 in C57BL / 6 mice bearing MC38 tumors. Definition

[0082] The term "halogen", as used herein, unless otherwise indicated, means fluoro, chloro, bromo or iodo. The preferred halogen groups include F, Cl and Br. The terms "haloC 1-6 alkyl", "haloC 2-6 alkenyl", "haloC 2- 6 alkynyl" and "haloC 1-6 alkoxy" mean a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 1-6 alkoxy in which one or more (in particular, 1 to 3) hydrogen atoms have been replaced by halogen atoms, especially fluorine or chlorine atoms. In some embodiment, preferred are fluoroC 1-6 alkyl, fluoroC 2-6 alkenyl, fluoroC 2-6 alkynyl and fluoroC 1-6 alkoxy groups, in particular fluoroC 1-3 alkyl, for example, CF 3 , CHF 2 , CH 2 F, CH 2 CH 2 F, CH 2 CHF 2 , CH 2 CF 3 and fluoroC 1-3 alkoxy groups, for example, OCF 3 , OCHF 2 , OCH 2 F, OCH 2 CH 2 F, OCH 2 CHF 2 or OCH 2 CF 3 , and most especially CF 3 , OCF 3 and OCHF 2 .

[0083] The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight branched or cyclic moieties. For example, alkyl radicals include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, cyclobutyl, 3-(2-methyl)butyl, 2-pentyl, 2-methylbutyl, neopentyl, cyclopentyl, n-hexyl, 2-hexyl, 2-methylpentyl and cyclohexyl. Similary, C 1-6 , as in C 1-6 alkyl is defined to identify the group as having 1, 2, 3, 4, 5 or 6 carbon atoms in a linear or branched arrangement.

[0084] The term "alkylene" means a difunctional group obtained by removal of a hydrogen atom from an alkyl group that is defined above. For example, methylene (i.e., -CH 2 -), ethylene (i.e., -CH 2 -CH 2 - or - CH(CH 3 )-) and propylene (i.e., -CH 2 -CH 2 - CH 2 -, -CH(-CH 2 -CH 3 )- or -CH 2 -CH(CH 3 )-).

[0085] The term "alkenyl" means a straight or branch-chained hydrocarbon radical containing one or more double bonds and typically from 2 to 20 carbon atoms in length. For example, "C 2-6 alkenyl" contains from 2 to 6 carbon atoms. Alkenyl group include, but are not limited to, for example, ethenyl, propenyl, butenyl, 2-methyl-2-buten-1-yl, hepetenyl, octenyl and the like.

[0086] The term "alkynyl" contains a straight or branch-chained hydrocarbon radical containing one or more triple bonds and typically from 2 to 20 carbon atoms in length. For example, "C 2-6 alkynyl" contains from 2 to 6 carbon atoms. Representative alkynyl groups include, but are not limited to, for example, ethynyl, 1-propynyl, 1-butynyl, heptynyl, octynyl and the like.

[0087] The term "alkoxy" radicals are oxygen ethers formed from the previously described alkyl groups.

[0088] The term "aryl", as used herein, unless otherwise indicated, refers to an unsubstituted or substituted mono or polycyclic aromatic ring system containing carbon ring atoms. The preferred aryls are mono cyclic or bicyclic 6-10 membered aromatic ring systems. Phenyl and naphthyl are preferred aryls.

[0089] The term "heterocyclyl", as used herein, unless otherwise indicated, refers to unsubstituted and substituted mono or polycyclic non-aromatic ring system containing one or more heteroatoms, which comprising moncyclic heterocyclic ring, bicyclic heterocyclic ring, bridged heterocyclic ring, fused heterocyclic ring or sipro heterocyclic ring. Preferred heteroatoms include N, O, and S, including N-oxides, sulfur oxides, and dioxides. Preferably the ring is three to ten membered and is either fully saturated or has one or more degrees of unsaturation. Multiple degrees of substitution, preferably one, two or three, are included within the present definition. Examples of such heterocyclic groups include, but are not limited to azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxopiperazinyl, oxopiperidinyl, oxoazepinyl, azepinyl, tetrahydrofuranyl, dioxolanyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydrooxazolyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone and oxadiazolyl.

[0090] The term "heteroaryl", as used herein, unless otherwise indicated, represents an aromatic ring system containing carbon(s) and at least one heteroatom. Heteroaryl may be monocyclic or polycyclic, substituted or unsubstituted. A monocyclic heteroaryl group may have 1 to 4 heteroatoms in the ring, while a polycyclic heteroaryl may contain 1 to 10 hetero atoms. A polycyclic heteroaryl ring may contain fused, spiro or bridged ring junction, for example, bycyclic heteroaryl is a polycyclic heteroaryl. Bicyclic heteroaryl rings may contain from 8 to 12 member atoms. Monocyclic heteroaryl rings may contain from 5 to 8 member atoms (cabons and heteroatoms). Examples of heteroaryl groups include, but are not limited to thienyl, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, triazolyl, pyridyl, pyridazinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, benzofuranyl, benzothienyl, benzisoxazolyl, benzoxazolyl, benzopyrazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl adeninyl, quinolinyl or isoquinolinyl.

[0091] The term "cycloalkyl" refers to a substituted or unsubstituted monocyclic ring, bicyclic ring bridged ring, fused ring, sipiro ring non-aromatic ring system onle containing carbon atoms. Examplary "cycloalkyl" groups includes but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and so on. wherein the term "substituted" refers to a group mentioned above in which one or more (preferably 1-6, more preferably 1-3) hydrogen atoms are each independently replaced with the same or different substituent(s). Typical substituents include, but are not limited to, T, C 1 - 6 alkyl, C 1 - 6 alkoxy, C 3-20 cycloalkyl, -OR 13 , SR 13 , =O, =S, -C(O)R 13 , -C(S)R 13 , =NR 13 , -C(O)OR 13 , -C(S)OR 13 , -NR 13 R 14 , - C(O)NR 13 R 14 , cyano, nitro, -S(O) 2 R 13 , -OS(O 2 )OR 13 , -OS(O) 2 R 13 , or -OP(O)(OR 13 )(OR 14 ); wherein each T is independently a halogen (F, Cl, Br or I), and R 13 and R 14 is independently selected from -H, C 1-6 alkyl and C 1-6 haloalkyl. In some embodiments, the substituent(s) is independently selected from the group consisting of -F, -Cl, -Br, -I, -OH, trifluromethoxy, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, CHF 2 , methoxy, ethoxy, propyloxy, iso-propyloxy, n-butyloxy, isobutyloxy, t-butyloxy, -SCH 3 , -SC 2 H 5 , formaldehyde group, -C(OCH 3 ), cyano, nitro,CF 3 ,-OCF 3 , amino, dimethylamino, methyl thio, sulfonyl and acetyl. Particularly preferred substituent(s) is -F, -Cl or -Br.

[0092] The term "composition", as used herein, is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combinations of the specified ingredients in the specified amounts. Accordingly, pharmaceutical compositions containing the compounds of the present invention as the active ingredient as well as methods of preparing the instant compounds are also part of the present invention. Furthermore, some of the crystalline forms for the compounds may exist as polymorphs. In addition, some of the compounds may form solvates with water (i.e., hydrates) or common organic solvents.

[0093] The compounds of the present invention may also be present in the form of pharmaceutically acceptable salt(s). For use in medicine, the salts of the compounds of this invention refer to non-toxic "pharmaceutically acceptable salt(s)". The pharmaceutically acceptable salt forms include pharmaceutically acceptable acidic / anionic or basic / cationic salts. The pharmaceutically acceptable acidic / anionic salt generally takes a form in which the basic nitrogen is protonated with an inorganic or organic acid. Representative organic or inorganic acids include hydrochloric, hydrobromic, hydriodic, perchloric, sulfuric, nitric, phosphoric, acetic, propionic, glycolic, lactic, succinic, maleic, fumaric, malic, tartaric, citric, benzoic, mandelic, methanesulfonic, hydroxyethanesulfonic, benzenesulfonic, oxalic, pamoic, 2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic, saccharinic or trifluoroacetic. Pharmaceutically acceptable basic / cationic salts include, and are not limited to aluminum, calcium, chloroprocaine, choline, diethanolamine, ethylenediamine, lithium, magnesium, potassium, sodium and zinc.

[0094] The present disclosure also provides the prodrugs of the compounds of this invention (not encompassed by the wording of the claims). In general, such prodrugs will be functional derivatives of the compounds that are readily converted in vivo into the required compound. Thus, in the methods of treatment of the present invention, the term "administering" shall encompass the treatment of the various disorders described with the compound specifically disclosed or with a compound which may not be specifically disclosed, but which converts to the specified compound in vivo after administration to the subject. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985.

[0095] It is intended that the definition of any substituent or variable at a particular location in a molecule be independent of its definitions elsewhere in that molecule. It is understood that substituents and substitution patterns on the compounds of this invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques know in the art as well as those methods set forth herein.

[0096] The present invention includes compounds described can contain one or more asymmetric centers and may thus give rise to diastereomers and optical isomers. The present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and pharmaceutically acceptable salts thereof.

[0097] The present invention includes all stereoisomers of the compound and pharmaceutically acceptable salts thereof. Further, mixtures of stereoisomers as well as isolated specific stereoisomers are also included. During the course of the synthetic procedures used to prepare such compounds or in using racemization or epimerization procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers.

[0098] The term "stereoisomer" as used in the present invention refers to an isomer in which atoms or groups of atoms in the molecule are connected to each other in the same order but differ in spatial arrangement, including conformational isomers and conformational isomers. The configuration isomers include geometric isomers and optical isomers, and optical isomers mainly include enantiomers and diastereomers. The invention includes all possible stereoisomers of the compound.

[0099] The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include deuterium and tritium. The isotopes of hydrogen can be denoted as 1< H(hydrogen), 2< H(deuterium) and 3< H(tritium). They are also commonly denoted as D for deuterium and T for tritium. In the application, CD 3 denotes a methyl group wherein all of the hydrogen atomsare deuterium. Isotopes of carbon include 13< C and 14< C.Isotopically-labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described herein, using an appropriate isotopically-labeled reagent in place of the non-labeled reagent.

[0100] When a tautomer of the compound exists, the present invention includes any possible tautomers and pharmaceutically acceptable salts thereof, and mixtures thereof, except where specifically stated otherwise.

[0101] When the compound and pharmaceutically acceptable salts thereof exist in the form of solvates or polymorphic forms, the present invention includes any possible solvates and polymorphic forms. A type of a solvent that forms the solvate is not particularly limited so long as the solvent is pharmacologically acceptable. For example, water, ethanol, propanol, acetone or the like can be used.

[0102] The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids. When the compound of the present invention is acidic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic bases, including inorganic bases and organic bases. When the compound of the present invention is basic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Since the compounds are intended for pharmaceutical use they are preferably provided in substantially pure form, for example at least 60% pure, more suitably at least 75% pure, especially at least 98% pure (% are on a weight for weight basis).

[0103] The pharmaceutical compositions of the present invention comprise a compound (or a pharmaceutically acceptable salt thereof) as an active ingredient, a pharmaceutically acceptable carrier and optionally other therapeutic ingredients or adjuvants. The compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions may be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.

[0104] In practice, the compounds or a prodrug or a metabolite or pharmaceutically acceptable salts thereof, of this invention can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g. oral or parenteral (including intravenous). Thus, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient. Further, the compositions can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion or as a water-in- oil liquid emulsion. In addition to the common dosage forms set out above, the compound or a pharmaceutically acceptable salt thereof, may also be administered by controlled release means and / or delivery devices. The compositions may be prepared by any of the methods of pharmacy. In general, such methods include a step of bringing into association the active ingredient with the carrier that constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both. The product can then be conveniently shaped into the desired presentation.

[0105] Thus, the pharmaceutical compositions of this invention may include a pharmaceutically acceptable carrier and a compound or a pharmaceutically acceptable salt. The compounds or pharmaceutically acceptable salts thereof, can also be included in pharmaceutical compositions in combination with one or more other therapeutically active compounds.

[0106] The pharmaceutical carrier employed can be, for example, a solid, liquid or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. In preparing the compositions for oral dosage form, any convenient pharmaceutical media may be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like may be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets may be coated by standard aqueous or nonaqueous techniques.

[0107] A tablet containing the composition of this invention may be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets may be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. Each tablet preferably contains from about 0.05mg to about 5g of the active ingredient and each cachet or capsule preferably containing from about 0.05mg to about 5g of the active ingredient. For example, a formulation intended for the oral administration to humans may contain from about 0.5mg to about 5g of active agent, compounded with an appropriate and convenient amount of carrier material which may vary from about 0.05 to about 95 percent of the total composition. Unit dosage forms will generally contain between from about 0.01mg to about 2g of the active ingredient, typically 0.01mg, 0.02mg, 1mg, 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, 10mg, 25mg, 50mg, 100mg, 200mg, 300mg, 400mg, 500mg, 600mg, 800mg or 1000mg.

[0108] Pharmaceutical compositions of the present invention suitable for parenteral administration may be prepared as solutions or suspensions of the active compounds in water. A suitable surfactant can be included such as, for example, hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Further, a preservative can be included to prevent the detrimental growth of microorganisms.

[0109] Pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. In all cases, the final injectable form must be sterile and must be effectively fluid for easy syringability. The pharmaceutical compositions must be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof.

[0110] Pharmaceutical compositions of the present invention can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder or the like. Further, the compositions can be in a form suitable for use in transdermal devices. These formulations may be prepared, utilizing a compound of this invention or a pharmaceutically acceptable salt thereof, via conventional processing methods. As an example, a cream or ointment is prepared by admixing hydrophilic material and water, together with about 0.05wt% to about 10wt% of the compound, to produce a cream or ointment having a desired consistency.

[0111] Pharmaceutical compositions of this invention can be in a form suitable for rectal administration wherein the carrier is a solid. It is preferable that the mixture forms unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories may be conveniently formed by first admixing the composition with the softened or melted carrier(s) followed by chilling and shaping in molds.

[0112] In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described above may include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including antioxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient. Compositions containing a compound or pharmaceutically acceptable salts thereof, may also be prepared in powder or liquid concentrate form.

[0113] Generally, dosage levels on the order of from about 0.001mg / kg to about 150mg / kg of body weight per day are useful in the treatment of the above-indicated conditions or alternatively about 0.05mg to about 7g per patient per day. For example, inflammation, cancer, psoriasis, allergy / asthma, disease and conditions of the immune system, disease and conditions of the central nervous system (CNS), may be effectively treated by the administration of from about 0.001 to 50mg of the compound per kilogram of body weight per day or alternatively about 0.05mg to about 3.5g per patient per day.

[0114] It is understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the particular disease undergoing therapy.

[0115] These and other aspects will become apparent from the following written description of the invention.Examples

[0116] The following examples are provided to better illustrate the present invention. All parts and percentages are by weight and all temperatures are degrees Celsius, unless explicitly stated otherwise. The following abbreviations have been used in the examples: DMFN,N-DimethylformamideEAEthyl acetateMeONaSodium methanolateMeOHMethanolDCMDichloromethaneDCE1,2-DichloroethaneEtOHEthanolTHFTetrahydrofuranMeCNAcetonitrileNMM4-MethylmorpholineDIPEAN,N-DiisopropylethylamineTEATriethylamineTs4-methyl benzenesulfonylHATU2-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateXtalFluor-EN,N-Diethyl-S,S-difluorosulfiliminium tetrafluoroborateTCFHN-(chloro(dimethylamino)methylene)-N-methylmethanaminium hexafluorophosphate (V)BOP1H-Benzotriazol-1-yloxytris(dimethylamino)phosphonium HexafluorophosphateRTRoom temperatureminminute(s)hhour(s)aqaqueoussatsaturatedFLASHMedium pressure chromatographPrep - TLCPreparative thin layer chromatographyPre-HPLCHigh pressure chromatograph

[0117] Intermediate A1 was prepared referring to the compound 3 in WO2017023774 in Scheme 1 at page 82.

[0118] The following compounds were synthesized using the above procedure or modification procedure with the corresponding starting materials. A2 A3 A4 A5 A6

[0119] Step a: To a solution of 7-Fluoroindole (308 mg, 2.279 mmol) and Ytterbium(III) triflate hydrate (219 mg, 343.119 µmol) in Chloroform (3 mL) was added (2S)-Methylglycidate (121 mg,1.185 mmol) under N 2 . The mixture was heated to 85°C and stirred for 3 h. The reaction mixture was cooled to RT. The reaction mixture was quenched with Na 2 CO 3 (aq) (10 mL), and adjusted the pH to 5-6 with 2M HCl. The aqueous layer was separated and extracted with DCM (2×10 mL). The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure. The residue was purified by silica chromatography eluting with EtOAc / Hexane(1:2) to afford methyl (2S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxy-propanoate (136 mg, 573.292 µmol). MS: m / z 238(M+H) +< .

[0120] Step b: To a solution of methyl (2S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxy-propanoate (136 mg, 573.292 µmol) in water (1 mL) was added LiOH (2M solution in water, 1 mL). The mixture was stirred for overnight at RT-60°C, Citric acid(solid) was added, diluted with water (5 mL) and extracted with EA (2×10 mL). The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure to afford (2S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxy-propanoic acid (165 mg, 739.247 µmol) which was used in next step without any further purification. MS: m / z (224) +< .

[0121] Step a: To a solution of Indole (302 mg, 2.578 mmol) in DMF (3 mL) was added NaH (217 mg, 9.043 mmol) at ice-water bath for 1h . (2S)-Methylglycidate (685 mg, 6.710 mmol) was added and the mixture was stirred over night at RT. The reaction mixture was quenched with H 2 O, and adjusted the pH to 3-4 with citric acid. The aqueous layers were extracted with EA. The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure. The residue was purified by FLASH with H 2 O / MeCN (5%-95%) to afford (S)-2-hydroxy-3-(1H-indol-1-yl)propanoic acid (222 mg, 1.082 mmol). MS: m / z 206(M+H) +< .

[0122] The following compounds were synthesized using the above procedure or modification procedure with the corresponding starting materials.

[0123] Step a: To a solution of Methyl (S)-(-)-lactate (1099 mg, 10.5567 mmol), Iodoethane (3726 mg, 23.8900 mmol) in Diethyl ether (10 mL) was added Ag 2 O (4772 mg, 20.5925 mmol) under N 2. The reaction mixture was stirred over night at RT by light-avoiding. The reaction mixture was monitored by TLC. The reaction mixture was filtered and concentrated under reduced pressure. The residue was dissolved by THF (3 mL), MeOH (3 mL), H 2 O (3 mL) and then the reaction mixture was added LiOH (246 mg, 10.2721 mmol). The reaction mixture was stirred for 3h at RT. The reaction mixture was monitored by TLC and adjusted the pH to 2 with 1N HCl. The reaction mixture was concentrated under reduced pressure to 5 mL. The aqueous layers were extracted with EA (3×10 mL). The combined organic layers were washed with saturated solution of NaCl (3×10 mL) and dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure to afford (S)-2-ethoxypropanoic acid (772 mg, 6.5351 mmol). MS: m / z 119(M+H) +< .

[0124] Step a: To a solution of 2-hydroxy-4-(methylthio)butanoic acid (0.68 g, 4.5274 mmol), CH 3 I (3.35 g, 23.6019 mmol) in Diethyl ether (10 mL) was added Ag 2 O (4.41 g, 19.0303 mmol) The reaction mixture was stirred over night at RT. The reaction mixture was monitored by LC-MS. The reaction mixture was filtered and concentrated under reduced pressure. The residue was dissolved by MeOH (6 mL), H 2 O (2 mL) and then the reaction mixture was added NaOH (318 mg, 7.9506 mmol). The reaction mixture was stirred for 3h at RT. The reaction mixture was monitored by TLC and adjusted the pH to 3 with 1M HCl. The reaction mixture was concentrated under reduced pressure to 5 mL. The aqueous layers were extracted with EA (3×10 mL). The combined organic layers were washed with saturated solution of NaCl (3×10 mL) and dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure to afford 2-methoxy-4-(methylthio)butanoic acid (128 mg, 779.4318 µmol). MS: m / z 165(M+H) +< .

[0125] Step a: To a solution of 2-hydroxy-3-(1H-indol-3-yl)propanoic acid (152 mg, 740.706 µmol) in THF (10 mL) was added NaH (55 mg, 2.292 mmol) The reaction mixture was stirred for 20 min at RT and then CH 3 I (370 mg, 2.607 mmol) was added. The reaction mixture was monitored by LC-MS. CH 3 I (358 mg, 2.522 mmol) was added again. The reaction mixture was monitored by LC-MS. The reaction mixture was stirred for 3h at 40°C. The reaction mixture was added H 2 O (5 mL) and extracted with EA (10 mL). The aqueous layers were combined and purified by FLASH with H 2 O / MeCN (0%-100%, 40min, C18). The product layers were concentrated under reduced pressure to afford 2-methoxy-3-(1-methyl-1H-indol-3-yl)propanoic acid (119 mg, 510.155 µmol). MS: m / z 234 (M+H) +< .

[0126] The following compounds were synthesized using the above procedure or modification procedure with the corresponding starting materials.

[0127] Step a: To a solution of methyl (S)-2-hydroxy-3-(1H-indol-3-yl)propanoate(2 g, 9.123 mmol) in DCM (20 mL) was added Imidazole(2061 mg, 30.274 mmol) and TBDMS-Cl (2980 mg, 19.772 mmol). The mixture was stirred for overnight at RT. The reaction mixture was quenched with Water (10 mL) and extracted with DCM (10 mL). The reaction mixture was separated and organic extracts were collected. The aqueous solution was extracted with DCM (2×10 mL). The residue was purified by wet column chromatography with EA / Hex (0-20%). The product's solution was concentrated under reduced pressure. The methyl (S)-2-((tertbutyldimethylsilyl)oxy)-3-(1H-indol-3-yl)propanoate (3099 mg) was obtained. MS: m / z 334(M+H) +< .

[0128] Step b: To a -78°C solution of methyl (S)-2-((tert-butyldimethylsilyl)oxy)-3-(1H-indol-3-yl)propanoate (3.099g, 9.292 mmol) in THF (30 mL) was added LiHMDS (10.5 mL, 10.491 mmol). The mixture was stirred for 30min at -78°C. Then Carbobenzyloxy chloride (4623 mg, 27.100 mmol) was dropped into the mixture at -78°C. The reaction mixture was stirred for 1h at this temperature. Quenched the reaction with sat. NH 4 Cl, and the aqueous solution was extracted with EA (2×10 mL). The combined organic extracts were washed with brine (3×10 mL), dried over anhydrous Na 2 SO 4 . The organic phase was concentrated under reduced pressure. The benzyl (S)-3-(2-((tert-butyldimethylsilyl)oxy)-3-methoxy-3-oxopropyl)-1H-indole-1- carboxylate (4345 mg) was obtained. MS: m / z 468(M+H) +< .

[0129] Step c: To a solution of benzyl(S)-3-(2-((tert-butyldimethylsilyl)oxy)-3-methoxy-3-oxopropyl)- 1H-indole-1- carboxylate (4.345 g, 9.292 mmol) in THF (30 mL) was added Tetrabutylammonium fluoride (5 mL). The mixture was stirred for overnight at RT. The reaction mixture was concentrated under reduced pressure. The residue was purified by FLASH with EA / Hex(0-60%). The product's solution was concentrated under reduced pressure. The benzyl 3-[(2S)-2-hydroxy-3-methoxy- 3-oxo-propyl]indole-1-carboxylate (2.21 g) was obtained. MS: m / z 354(M+H) +< .

[0130] Step d: To a solution of benzyl 3-[(2S)-2-hydroxy-3-methoxy-3-oxo-propyl]indole-1-carboxylate(103 mg, 291.481 µmol), and 4A molecular sieve in CH 3 I (1mL) was added Silver oxide(216 mg, 932.098 µmol). The mixture was stirred for overnight at RT. The reaction mixture was concentrated under reduced pressure. The reaction mixture was diluted with EA (5mL) and filtered, the filtrate was concentrated to afford benzyl (S)-3-(2,3-dimethoxy-3-oxopropyl)-1H-indole-1- carboxylate (107.088 mg, 100.000% yield). MS: m / z 368(M+H) +< .

[0131] Step e: To a solution of benzyl(S)-3-(2,3-dimethoxy-3-oxopropyl)-1H-indole-1-carboxylate (0.107g, 291.240 µmol) in THF (5 mL) and MeOH(5mL) was added NaOH(3mL, 3M / L). The mixture was stirred for 1h at RT. The reaction mixture was adjusted the pH to 3 with 1M HCl. The aqueous solution was extracted with EA (2×10 mL). The combined organic extracts were washed with brine (3×10 mL), dried over anhydrous Na 2 SO 4 . The organic phase was concentrated under reduced pressure and (S)-3-(1H-indol-3-yl)-2-methoxypropanoic acid (71 mg) was obtained. MS: m / z 220(M+H) +< .

[0132] The following compounds were synthesized using intermediate D1 and the above procedure or modification procedure with the corresponding starting materials. EXAMPLE 1 Isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate (Compound 1)

[0133]

[0134] To a solution of (2S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxy-propanoic acid (0.165 g,739.247 µmol) and isopropyl (2S)-2-amino-6-diazo-5-oxo-hexanoate(123 mg, 576.834 µmol) in DCM (2 mL) was added N,N'-Diisopropylcarbodiimide (95 mg,752.779 µmol), 2,4,6-Collidine (115 mg,949.008 µmol) andEthyl cyanoglyoxylate-2-oxime (83 mg,584.044 µmol) at 0°C. The mixture was stirred at RT for 16 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by pre-HPLC, and concentrated under reduced pressure to afford isopropyl (2S)-6-diazo-2-[[(2S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxy-propanoyl]amino]-5-oxo-hexanoate (41.6 mg, 99.422 µmol) by lyophilization. MS: m / z 419(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 8.47 - 8.39 (m, 1H), 7.47 (d, J = 7.9 Hz, 1H), 7.21 - 7.19 (m, 1H), 7.16 (d, J = 7.8 Hz, 1H), 7.05 (td, J = 7.9, 4.8 Hz, 1H), 6.93 (dd, J = 10.8, 7.8 Hz, 1H), 5.09 (s, 1H), 5.03 (dt, J = 12.5, 6.3 Hz, 1H), 4.53 - 4.45 (m, 1H), 4.43 (s, 1H), 3.29 (ddd, J = 21.3, 14.8, 5.4 Hz, 2H), 2.73 - 2.60 (m, 1H), 2.43 - 2.25 (m, 1H), 2.18 - 1.98 (m, 2H), 1.97 - 1.80 (m, 1H), 1.30 - 1.22 (m, 6H).EXAMPLE 2 Isopropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate (Compound 2)

[0135]

[0136] To a solution of (S)-2-methoxypropanoic acid (267 mg, 2.565 mmol) and isopropyl (2S)-2-amino-6-diazo-5-oxo-hexanoate(0.152 g, 712.835 µmol) in DMF (5 mL) was added N,N'-Diisopropylcarbodiimide (327 mg, 2.591 mmol), 2,4,6-Collidine (412 mg, 3.400 mmol) and Ethyl cyanoglyoxylate-2-oxime (375 mg, 2.639 mmol) at 0°C. The mixture was stirred at RT for 15 h. The reaction mixture was quenched with saturated NH 4 Cl (50 mL) and extracted with EA (20 mL×3). The combined organic layers were washed with brine (50 mL×3) and concentrated under reduced pressure. The residue was purified by pre-HPLC (C18, MeCN / H2O=5-100%, 40min) and concentrated under reduced pressure to afford isopropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate (60.2 mg, 201.1211 µmol, easily dissolved in water). MS: m / z 300(M+H) -< , 1< H NMR (400 MHz, CDCl 3 ) δ 7.22 - 7.08 (m, 1H), 5.12 - 5.01 (m, 1H), 4.57 (td, J = 8.7, 4.8 Hz, 1H), 3.77 (dt, J = 6.7, 5.7 Hz, 1H), 3.45 (s, 3H), 2.82 - 2.58 (m, 1H), 2.50 - 2.22 (m, 2H), 2.09 - 1.85 (m, 1H), 1.44 - 1.35 (m, 3H), 1.31 - 1.26 (m, 6H).EXAMPLE 3 Methyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate (Compound 3)

[0137]

[0138] To a solution of (S)-2-methoxypropanoic acid (2.06 g, 19.7879 mmol) and methyl (S)-2-amino-6-diazo-5-oxohexanoate (2308 mg, 12.4635 µmol) in DMF (5 mL) was added NMM (3.73 g, 36.8770 mmol) and HATU (6.26 g, 16.4637 mmol) at 0°C. The mixture was stirred at RT for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by pre-HPLC (C18, MeCN / H 2 O=0-100%, 40 min) and concentrated under reduced pressure to afford methyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate (2.87 g, 10.5799 mmol, easily dissolved in water). MS: m / z 272(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 4.46 (dd, J = 8.9, 4.8 Hz, 1H), 3.79 - 3.74 (m, 1H), 3.72 (s, 3H), 3.40 (s, 3H), 2.43 (s, 2H), 2.33 - 2.15 (m, 1H), 2.08 - 1.90 (m, 1H), 1.33 (d, J = 6.7 Hz, 3H).EXAMPLE 4(S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoic acid (Compound 4)

[0139]

[0140] To a solution of methyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate (0.96 g, 3.5389 mmol) in THF (10 mL) was added a solution ofNaOH (176 mg, 4.4003 mmol) in water (5 mL) at 0°C. The mixture was stirred at RT for 40 min. The reaction mixture was concentrated under reduced pressure. The residue was purified by pre-HPLC (C18, MeCN / H 2 O=0-80%, 30 min) and concentrated under reduced pressure to afford (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoic acid (866 mg, 3.3665 mmol, easily dissolved in water). MS: m / z 258(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 4.27 (t, J = 5.8 Hz, 1H), 3.72 (q, J = 6.6 Hz, 1H), 3.40 (s, 3H), 2.46 - 2.27 (m, 2H), 2.28 - 2.13 (m, 1H), 2.06 - 1.91 (m, 1H), 1.33 (d, J= 6.7 Hz, 3H).EXAMPLE 5 Isopropyl (S)-2-((S)-2-acetoxy-3-(7-fluoro-1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate (Compound 5)

[0141]

[0142] To a solution of isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-hydroxypropanamido)-5-oxohexanoate (0.166 g, 396.7325 µmol) in DMF (3.5 mL) was added pyridine (189 mg, 2.3894 mmol) and acetic anhydride (104 mg, 1.0187 mmol) at RT. The mixture was stirred at RT for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by pre-HPLC (C18, MeCN / H 2 O=2-80%) and concentrated under reduced pressure to afford isopropyl (S)-2-((S)-2-acetoxy-3-(7-fluoro-1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate (75.2 mg, 163.3196 µmol). MS: m / z 461(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.39 (d, J = 7.9 Hz, 1H), 7.17 (s, 1H), 6.96 (dd, J = 13.4, 6.4 Hz, 1H), 6.88 - 6.76 (m, 1H), 5.24 (t, J = 5.4 Hz, 1H), 4.96 (dt, J = 12.4, 6.3 Hz, 1H), 4.27 (d, J = 8.7 Hz, 1H), 3.28 (d, J = 5.6 Hz, 2H), 2.26 - 2.13 (m, 1H), 2.10 (s, 3H), 2.05 (d, J = 10.2 Hz, 2H), 1.88 - 1.75 (m, 1H), 1.22 (t, J = 6.8 Hz, 6H).EXAMPLE 6 Ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate (Compound 6)

[0143]

[0144] To a solution of (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoic acid (104 mg, 404.2870 µmol) and EtOH (96 mg, 2.0839 mmol) in DMF (5 mL) was added NMM (117 mg, 1.1567 mmol) and HATU (237 mg, 623.3081 µmol) at 0°C. The mixture was stirred at RT for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by pre-HPLC (C18, MeCN / H 2 O=0-100%, 30 min) and concentrated under reduced pressure to afford ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate (0.0332 g, 116.3705 µmol, easily dissolved in water). MS: m / z 286(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 4.49 - 4.35 (m, 1H), 4.23 - 4.13 (m, 2H), 3.83 - 3.71 (m, 1H), 3.44 - 3.35 (m, 3H), 2.43 (s, 2H), 2.30 - 2.15 (m, 1H), 2.08 - 1.93 (m, 1H), 1.36 - 1.31 (m, 3H), 1.29 - 1.24 (m, 3H).

[0145] The following compounds were synthesized using the above procedure or modification procedure of the aboved schemes with the corresponding starting materials. Comp oundStructureIUPAC Name 1< HNMR & MS: (M+H) +< 7 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(7-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoateMS: m / z 431(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 8.41 (s, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.10 (d, J = 2.2 Hz, 1H), 7.04 (t, J = 7.9 Hz, 1H), 6.65 (d, J = 7.7 Hz, 1H), 5.08 - 4.95 (m, 2H), 4.47 (td, J = 8.1, 4.3 Hz, 1H), 4.40 (dd, J = 10.6, 4.9 Hz, 1H), 3.94 (s, 3H), 3.26 (ddd, J = 21.3, 14.7, 5.5 Hz, 2H), 2.66 (d, J = 4.9 Hz, 1H), 2.15 - 2.01 (m, 2H), 2.01 - 1.80 (m, 2H), 1.24 (dd, J = 7.6, 6.4 Hz, 6H).8 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoateMS: m / z 401(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 8.19 (d, J = 20.1 Hz, 1H), 7.70 (t, J = 8.6 Hz, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.24 (t, J = 7.5 Hz, 1H), 7.19 - 6.98 (m, 3H), 5.03 (dd, J = 13.1, 7.0 Hz, 2H), 4.54 (s, 1H), 4.44 (s, 1H), 3.33 (dd, J = 37.0, 16.6 Hz, 2H), 2.62 - 2.51 (m, 1H), 2.39 - 2.24 (m, 1H), 2.15 - 2.05 (m, 1H), 2.01 - 1.85 (m, 1H), 1.27 (t, J = 5.9 Hz, 6H).9 isopropyl (S)-6-diazo-2-(2-methoxyacetamido) -5-oxohexanoate28610 isopropyl (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoateMS: m / z 300(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.08 - 4.95 (m, 1H), 4.46 - 4.37 (m, 1H), 4.02 - 3.89 (m, 2H), 3.67 - 3.47 (m, 2H), 2.44 (s, 2H), 2.29 - 2.11 (m, 1H), 2.10 - 1.92 (m, 1H), 1.26 (s, 9H).11 isopropyl (S)-6-diazo-2-((S)-2-hydroxypropanami do)-5-oxohexanoateMS: m / z 286(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.09 - 4.95 (m, 1H), 4.42 - 4.32 (m, 1H), 4.18 - 4.08 (m, 1H), 2.42 (s, 2H), 2.30 - 2.13 (m, 1H), 2.08 - 1.88 (m, 1H), 1.40 - 1.31 (m, 3H), 1.26 (s, 6H).12 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-phenylpropanamid o)-5-oxohexanoateMS: m / z 362(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.34 - 7.12 (m, 5H), 5.05 - 4.92 (m, 1H), 4.38 - 4.22 (m, 2H), 3.09 (d, 1H), 2.94 - 2.76 (m, 1H), 2.27 - 1.97 (m, 3H), 1.94 - 1.77 (m, 1H), 1.25 (d, J = 3.7 Hz, 6H).13 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-phenylpropanamid o)-5-oxohexanoateMS: m / z 376(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 7.35 - 7.17 (m, 9H), 7.02 (d, J = 8.5 Hz, 1H), 5.15 (s, 1H), 5.02 (dt, J = 12.3, 6.3 Hz, 1H), 4.55 - 4.44 (m, 1H), 3.95 - 3.87 (m, 1H), 3.46 - 3.38 (m, 3H), 3.21 - 3.09 (m, 1H), 3.01 - 2.89 (m, 1H), 2.19 - 1.91 (m, 3H), 1.89 - 1.76 (m, 1H), 1.24 (t, J = 6.2 Hz, 6H).14 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-4-methylpentanamido )-5-oxohexanoateMS: m / z 328(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 7.08 (d, J = 7.9 Hz, 1H), 5.23 (s, 1H), 5.04 - 4.91 (m, 1H), 4.46 (td, J = 8.4, 4.7 Hz, 1H), 4.13 - 4.03 (m, 1H), 2.73 - 2.55 (m, 1H), 2.41 - 2.28 (m, 1H), 2.20 - 2.09 (m, 1H), 2.02 - 1.90 (m, 1H), 1.87 - 1.74 (m, 1H), 1.57 - 1.39 (m, 2H), 1.22 - 1.16 (m, 6H), 0.90 (dd, J = 6.6, 3.1 Hz, 6H).15 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-phenylacetamido)-5-oxohexanoateMS: m / z 348(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.48 (d, J = 6.8 Hz, 2H), 7.42 - 7.20 (m, 3H), 5.18 - 4.91 (m, 2H), 4.46 - 4.18 (m, 1H), 2.34 (s, 2H), 2.28 - 2.08 (m, 1H), 2.11 - 1.90 (m, 1H), 1.21 (s, 6H).16 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-phenylacetamido)-5-oxohexanoateMS: m / z 362(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.40 (d, J = 34.5 Hz, 5H), 4.99 (s, 1H), 4.67 (s, 1H), 4.35 (s, 1H), 3.43 (s, 3H), 2.33 (s, 2H), 2.18 (s, 1H), 1.99 (s, 1H), 1.24 (s, 6H).17 isopropyl (S)-2-((S)-2-(2-cyanoacetoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoateMS: m / z 468(M+H) +< , 1< H NMR (400 M Hz, CD 3 OD) δ 7.67 - 7.53 (m , 1H), 7.39 - 7.26 (m, 1H), 7. 22 - 7.14 (m, 1H), 7.14 - 6.8 8 (m, 2H), 5.40 - 5.27 (m, 1H ), 5.03 - 4.90 (m, 1H), 4.31 - 4.11 (m, 1H), 3.32 (s, 1H), 3. 24 - 3.08 (m, 1H), 2.22 - 1.5 8 (m, 4H), 1.22 (s, 6H).18 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(pivaloyloxy)propa namido)-6-diazo-5-oxohexanoateMS: m / z 485(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.62 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.15 - 7.08 (m, 2H), 7.03 (t, J = 7.4 Hz, 1H), 5.59 (s, 1H), 5.21 (t, J = 6.0 Hz, 1H), 4.99 (dt, J = 12.4, 6.1 Hz, 1H), 4.35 - 4.26 (m, 1H), 3.31 - 3.26 (m, 2H), 2.31 - 2.17 (m, 1H), 2.17 - 1.98 (m, 2H), 1.92 - 1.78 (m, 1H), 1.25 (t, J = 6.3 Hz, 6H), 1.18 (s, 9H).19 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-1-yl)propanamido)-5-oxohexanoateMS: m / z 401(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 7.62 (d, J = 7.8 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.16 (s, 1H), 7.11 (t, J = 7.4 Hz, 1H), 6.52 (s, 1H), 5.22 (s, 1H), 5.02 (dt, J = 12.3, 6.3 Hz, 1H), 4.67 - 4.56 (m, 1H), 4.52 - 4.38 (m, 2H), 4.35 - 4.19 (m, 1H), 2.97 - 2.88 (m, 1H), 2.33 - 2.20 (m, 1H), 2.19 - 2.07 (m, 1H), 2.01 - 1.86 (m, 1H), 1.29 - 1.22 (m, 6H).20 isopropyl (S)-6-diazo-2-((S)-2-(4-fluorophenyl)-2-hydroxyacetamido) -5-oxohexanoateMS: m / z 366(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.52 (t, J = 6.1 Hz, 2H), 7.0 9 (td, J = 8.8, 3.0 Hz, 2H), 5.0 6 (s, 1H), 5.00 (dq, J = 12.9, 6 .4 Hz, 1H), 4.38 (td, J = 9.5, 5 .0 Hz, 1H), 2.56 - 2.32 (m, 2 H), 2.30 - 2.14 (m, 1H), 2.12 - 1.89 (m, 1H), 1.27 - 1.09 ( m, 6H).21 isopropyl (S)-6-diazo-2-(2-((4-fluorobenzyl)oxy)a cetamido)-5-oxohexanoateMS: m / z 380(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 7.40 - 7.30 (m, 2H), 7.06 (t, J = 8.4 Hz, 2H), 5.13 - 4.98 ( m, 1H), 4.67 - 4.48 (m, 3H), 4.06 - 3.87 (m, 2H), 2.57 - 2. 30 (m, 2H), 2.31 - 1.85 (m, 2 H), 1.32 - 1.19 (m, 6H).22 isopropyl (S)-2-((S)-3-(7-cyano-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate42623 isopropyl (S)-2-((S)-3-(6-cyano-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate42624 isopropyl (S)-2-((S)-3-(5-cyano-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate42625 isopropyl (S)-2-((S)-3-(4-cyano-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate42626 isopropyl (S)-2-((S)-3-(7-cyano-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44027 isopropyl (S)-2-((S)-3-(6-cyano-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44028 isopropyl (S)-2-((S)-3-(5-cyano-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44029 isopropyl (S)-2-((S)-3-(4-cyano-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44030 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(6-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate43131 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(5-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate43132 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(4-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate43133 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(6-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate44534 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(5-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate44535 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(4-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate44536 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(7-methoxy-1H-indol-3-yl)propanamido)-5-oxohexanoate44537 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1-methyl-1H-imidazol-4-yl)propanamido)-5-oxohexanoate38038 isopropyl (2S)-6-diazo-2-(2-hydroxy-3-(1H-indol-3-yl)-2-methylpropanamid o)-5-oxohexanoate41539 isopropyl (S)-6-diazo-2-((S)-3-(6-fluoro-1H-indol-3-yl)-2-hydroxypropanami do)-5-oxohexanoate41940 isopropyl (S)-6-diazo-2-((S)-3-(5-fluoro-1H-indol-3-yl)-2-hydroxypropanami do)-5-oxohexanoate41941 isopropyl (S)-6-diazo-2-((S)-3-(4-fluoro-1H-indol-3-yl)-2-hydroxypropanami do)-5-oxohexanoate41942 isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate43343 isopropyl (S)-6-diazo-2-((S)-3-(6-fluoro-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate43344 isopropyl (S)-6-diazo-2-((S)-3-(5-fluoro-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate43345 isopropyl (S)-6-diazo-2-((S)-3-(4-fluoro-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate43346 isopropyl (S)-2-((S)-3-(7-chloro-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate43547 isopropyl (S)-2-((S)-3-(6-chloro-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate43548 isopropyl (S)-2-((S)-3-(5-chloro-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate43549 isopropyl (S)-2-((S)-3-(4-chloro-1H-indol-3-yl)-2-hydroxypropanami do)-6-diazo-5-oxohexanoate43550 isopropyl (S)-2-((S)-3-(7-chloro-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44951 isopropyl (S)-2-((S)-3-(6-chloro-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44952 isopropyl (S)-2-((S)-3-(5-chloro-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44953 isopropyl (S)-2-((S)-3-(4-chloro-1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoate44954 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(7-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate41555 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(6-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate41556 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(5-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate41557 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(4-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate41558 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(7-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate42959 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(6-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate42960 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(5-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate42961 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(4-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoate42962 isopropyl (S)-6-diazo-2-((S)-3-(7-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanami do)-5-oxohexanoate44463 isopropyl (S)-6-diazo-2-((S)-3-(6-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanami do)-5-oxohexanoate44464 isopropyl (S)-6-diazo-2-((S)-3-(5-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanami do)-5-oxohexanoate44465 isopropyl (S)-6-diazo-2-((S)-3-(4-(dimethylamino)-1H-indol-3-yl)-2-hydroxypropanami do)-5-oxohexanoate44466 isopropyl (S)-6-diazo-2-((S)-3-(7-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate45867 isopropyl (S)-6-diazo-2-((S)-3-(6-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate45868 isopropyl (S)-6-diazo-2-((S)-3-(5-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate45869 isopropyl (S)-6-diazo-2-((S)-3-(4-(dimethylamino)-1H-indol-3-yl)-2-methoxypropanami do)-5-oxohexanoate45870 S-isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanethioateMS: 417(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.63 (d, J = 8.0 Hz, 1H), 7.33 (t, J = 8.8 Hz, 1H), 7.17 (s, 1H), 7.10 (t, J = 7.6 Hz, 1H), 7.01 (m, 1H), 5.24 (s, 1H), 4.44 (t, J = 4.8 Hz, 1H), 4.31 (m, 1H), 3.60 - 3.47 (m, 1H), 3.26 - 3.17 (m, 2H), 2.11 (s, 1H), 2.03 - 1.87 (m, 1H), 1.66 (m, 2H), 1.28 (m, 3H), 1.27 (d, J = 2.6 Hz, 3H).71 isopropyl (S)-6-diazo-2-((S)-2-ethoxypropanamido )-5-oxohexanoateMS: 314(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 5.01 (dt,J = 12.5, 6.3 Hz, 1H), 4.39 (dd, J = 9.0, 4.9 Hz, 1H), 3.84 (q, J = 6.8 Hz, 1H), 3.66 - 3.45 (m, 2H), 2.43 (s, 2H), 2.27 - 1.92 (m, 2H), 1.33 (d, J = 6.8 Hz, 3H), 1.28 - 1.21 (m, 9H).72 isopropyl (S)-6-diazo-2-((S)-2-isopropoxypropana mido)-5-oxohexanoate32873 isopropyl (S)-2-((S)-2-cyclopropoxypropa namido)-6-diazo-5-oxohexanoate32674 isopropyl (S)-6-diazo-2-(2-hydroxyacetamido) -5-oxohexanoateMS: 272(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.02 (dt, J = 12.5, 6.2 Hz, 1H), 4.44 (dd, J = 8.7, 5.1 Hz, 1H), 4.01 (s, 2H), 2.44 (s, 2H), 2.30 - 1.95 (m, 2H), 1.26 (d, J = 6.2 Hz, 6H).75 isopropyl (S)-2-(2-cyclopropoxyaceta mido)-6-diazo-5-oxohexanoate31276 isopropyl (S)-6-diazo-2-((S)-2-hydroxybutanamid o)-5-oxohexanoate30077 isopropyl (S)-6-diazo-2-((S)-2-methoxybutanamid o)-5-oxohexanoateMS: 314(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 5.02 (dt, J = 12.3, 6.3 Hz, 1H), 4.41 (dd, J = 9.3, 4.8 Hz, 1H), 3.62 - 3.55 (m, 1H), 3.41 (s, 3H), 2.44 (s, 2H), 2.27 - 1.91 (m, 2H), 1.86 - 1.59 (m, 2H), 1.26 (dd, J = 6.1, 3.4 Hz, 6H), 0.95 (t, J = 7.4 Hz, 3H).78 isopropyl (S)-6-diazo-2-((S)-2-ethoxybutanamido) -5-oxohexanoate32879 isopropyl (S)-6-diazo-2-((S)-2-isopropoxybutanam ido)-5-oxohexanoate34280 isopropyl (S)-2-((S)-2-cyclopropoxybutan amido)-6-diazo-5-oxohexanoate34081 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido) -5-oxohexanoateMS: 314(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.80 (s, 1H), 5.01 (dt,J = 12.5, 6.3 Hz, 1H), 4.39 (dd, J = 8.7, 5.1 Hz, 1H), 3.86 (d, J = 3.8 Hz, 1H), 2.43 (s, 2H), 2.25 - 1.91 (m, 3H), 1.30 - 1.21 (m, 6H), 1.01 (d, J = 6.9 Hz, 3H), 0.87 (d, J = 6.8 Hz, 3H).82 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-methylbutanamido) -5-oxohexanoateMS: 328(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.02 (dt, J = 12.5, 6.2 Hz, 1H), 4.41 (dd, J = 9.2, 4.9 Hz, 1H), 3.41 (s, 3H), 3.38 (d,J = 5.2 Hz, 1H), 2.45 (s, 2H), 2.26 - 2.14 (m, 1H), 2.06 - 1.92 (m, 2H), 1.26 (dd, J = 6.1, 3.8 Hz, 6H), 0.98 (d, J = 6.9 Hz, 3H), 0.94 (d, J = 6.8 Hz, 3H).83 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-methylbutanamido) -5-oxohexanoate34284 isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3-methylbutanamido) -5-oxohexanoate35685 isopropyl (S)-2-((S)-2-cyclopropoxy-3-methylbutanamido) -6-diazo-5-oxohexanoate35486 isopropyl (S)-6-diazo-2-((2S,3R)-2-hydroxy-3-methylpentanamido )-5-oxohexanoate32887 isopropyl (S)-6-diazo-2-((2S,3R)-2-methoxy-3-methylpentanamido )-5-oxohexanoate34288 isopropyl (S)-6-diazo-2-((2S,3R)-2-ethoxy-3-methylpentanamido )-5-oxohexanoate35689 isopropyl (S)-6-diazo-2-((2S,3R)-2-isopropoxy-3-methylpentanamido )-5-oxohexanoate37090 isopropyl (S)-2-((2S,3R)-2-cyclopropoxy-3-methylpentanamido )-6-diazo-5-oxohexanoate36891 isopropyl (S)-6-diazo-2-((S)-2-hydroxypentanamid o)-5-oxohexanoate31492 isopropyl (S)-6-diazo-2-((S)-2-methoxypentanami do)-5-oxohexanoate32893 isopropyl (S)-6-diazo-2-((S)-2-ethoxypentanamido )-5-oxohexanoate34294 isopropyl (S)-6-diazo-2-((S)-2-isopropoxypentana mido)-5-oxohexanoate35695 isopropyl (S)-2-((S)-2-cyclopropoxypenta namido)-6-diazo-5-oxohexanoate35496 isopropyl (S)-6-diazo-2-((S)-2-methoxy-4-methylpentanamido )-5-oxohexanoate34297 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-4-methylpentanamido )-5-oxohexanoate35698 isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-4-methylpentanamido )-5-oxohexanoate37099 isopropyl (S)-2-((S)-2-cyclopropoxy-4-methylpentanamido )-6-diazo-5-oxohexanoate368100 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3,3-dimethylbutanamid o)-5-oxohexanoate328101 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3,3-dimethylbutanamid o)-5-oxohexanoate342102 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3,3-dimethylbutanamid o)-5-oxohexanoate356103 isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3,3-dimethylbutanamid o)-5-oxohexanoate370104 isopropyl (S)-2-((S)-2-cyclopropoxy-3,3-dimethylbutanamid o)-6-diazo-5-oxohexanoate368105 isopropyl (S)-6-diazo-2-((S)-2-hydroxyhexanamid o)-5-oxohexanoate328106 isopropyl (S)-6-diazo-2-((S)-2-methoxyhexanamid o)-5-oxohexanoate342107 isopropyl (S)-6-diazo-2-((S)-2-ethoxyhexanamido) -5-oxohexanoate356108 isopropyl (S)-6-diazo-2-((S)-2-isopropoxyhexana mido)-5-oxohexanoate370109 isopropyl (S)-2-((S)-2-cyclopropoxyhexan amido)-6-diazo-5-oxohexanoate368110 isopropyl (S)-2-((S)-2-cyclopentyl-2-hydroxyacetamido) -6-diazo-5-oxohexanoate340111 isopropyl (S)-2-((S)-2-cyclopentyl-2-methoxyacetamido) -6-diazo-5-oxohexanoate354112 isopropyl (S)-2-((S)-2-cyclopentyl-2-ethoxyacetamido)-6-diazo-5-oxohexanoate368113 isopropyl (S)-2-((S)-2-cyclopentyl-2-isopropoxyacetami do)-6-diazo-5-oxohexanoate382114 isopropyl (S)-2-((S)-2-cyclopentyl-2-cyclopropoxyaceta mido)-6-diazo-5-oxohexanoate380115 isopropyl (S)-2-((S)-3-cyclopentyl-2-hydroxypropanami do)-6-diazo-5-oxohexanoate354116 isopropyl (S)-2-((S)-3-cyclopentyl-2-methoxypropanami do)-6-diazo-5-oxohexanoate368117 isopropyl (S)-2-((S)-3-cyclopentyl-2-ethoxypropanamido )-6-diazo-5-oxohexanoate382118 isopropyl (S)-2-((S)-3-cyclopentyl-2-isopropoxypropana mido)-6-diazo-5-oxohexanoate396119 isopropyl (S)-2-((S)-3-cyclopentyl-2-cyclopropoxypropa namido)-6-diazo-5-oxohexanoate394120 isopropyl (S)-2-((S)-2-cyclohexyl-2-hydroxyacetamido) -6-diazo-5-oxohexanoate354121 isopropyl (S)-2-((S)-2-cyclohexyl-2-methoxyacetamido) -6-diazo-5-oxohexanoate368122 isopropyl (S)-2-((S)-2-cyclohexyl-2-ethoxyacetamido)-6-diazo-5-oxohexanoate382123 isopropyl (S)-2-((S)-2-cyclohexyl-2-isopropoxyacetami do)-6-diazo-5-oxohexanoate396124 isopropyl (S)-2-((S)-2-cyclohexyl-2-cyclopropoxyaceta mido)-6-diazo-5-oxohexanoate394125 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-2-phenylacetamido)-5-oxohexanoate376126 isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-2-phenvlacetamido)-5-oxohexanoate390127 isopropyl (S)-2-((S)-2-cyclopropoxy-2-phenylacetamido)-6-diazo-5-oxohexanoate388128 isopropyl (S)-6-diazo-2-((S)-2-(4-fluorophenyl)-2-methoxyacetamido) -5-oxohexanoate380129 isopropyl (S)-2-((S)-2-(4-chlorophenyl)-2-methoxyacetamido) -6-diazo-5-oxohexanoate396130 isopropyl (S)-2-((S)-2-(4-chlorophenyl)-2-hydroxyacetamido) -6-diazo-5-oxohexanoate382131 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(4-methoxyphenyl)ace tamido)-5-oxohexanoate378132 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(4-methoxyphenyl)ace tamido)-5-oxohexanoate392133 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(4-hydroxyphenyl)acet amido)-5-oxohexanoate364134 isopropyl (S)-6-diazo-2-((S)-2-(4-hydroxyphenyl)-2-methoxyacetamido) -5-oxohexanoate378135 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(p-tolyl)acetamido)-5-oxohexanoate362136 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(p-tolyl)acetamido)-5-oxohexanoate376137 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-phenylpropanamido )-5-oxohexanoate390138 isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3-phenylpropanamido )-5-oxohexanoate404139 isopropyl (S)-2-((S)-2-cyclopropoxy-3-phenylpropanamido )-6-diazo-5-oxohexanoate402140 isopropyl (S)-6-diazo-2-((S)-3-(4-fluorophenyl)-2-hydroxypropanami do)-5-oxohexanoate380142 isopropyl (S)-6-diazo-2-((S)-3-(4-fluorophenyl)-2-methoxypropanami do)-5-oxohexanoate394143 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(4-fluorophenyl)propa namido)-5-oxohexanoate408144 isopropyl (S)-6-diazo-2-((S)-3-(4-fluorophenyl)-2-isopropoxypropana mido)-5-oxohexanoate422145 isopropyl (S)-2-((S)-2-cyclopropoxy-3-(4-fluorophenyl)propa namido)-6-diazo-5-oxohexanoate420146 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(4-hydroxyphenyl)pro panamido)-5-oxohexanoate378147 isopropyl (S)-6-diazo-2-((S)-3-(4-hydroxyphenyl)-2-methoxypropanami do)-5-oxohexanoate392148 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(4-hydroxyphenyl)pro panamido)-5-oxohexanoate406149 isopropyl (S)-6-diazo-2-((S)-3-(4-hydroxyphenyl)-2-isopropoxypropana mido)-5-oxohexanoate420150 isopropyl (S)-2-((S)-2-cyclopropoxy-3-(4-hydroxyphenyl)pro panamido)-6-diazo-5-oxohexanoate418151 isopropyl (S)-6-diazo-2-(1-hydroxycyclobutan e-1-carboxamido)-5-oxohexanoate312152 isopropyl (S)-6-diazo-2-(1-methoxycyclobutan e-1-carboxamido)-5-oxohexanoate326153 isopropyl (S)-6-diazo-2-(3-hydroxyoxetane-3-carboxamido)-5-oxohexanoate314154 isopropyl (S)-6-diazo-2-(3-methoxyoxetane-3-carboxamido)-5-oxohexanoate328155 isopropyl (S)-6-diazo-2-(1-hydroxycyclopenta ne-1-carboxamido)-5-oxohexanoate326156 isopropyl (S)-6-diazo-2-(1-methoxycyclopenta ne-1-carboxamido)-5-oxohexanoate340157 isopropyl (2S)-6-diazo-2-(3-hydroxytetrahydrof uran-3-carboxamido)-5-oxohexanoate328158 isopropyl (2S)-6-diazo-2-(3-methoxytetrahydrof uran-3-carboxamido)-5-oxohexanoate342159 isopropyl (S)-6-diazo-2-(1-hydroxycyclohexan e-1-carboxamido)-5-oxohexanoate340160 isopropyl (S)-6-diazo-2-(1-methoxycyclohexa ne-1-carboxamido)-5-oxohexanoate354161 isopropyl (S)-6-diazo-2-(4-hydroxy-1-methylpiperidine-4-carboxamido)-5-oxohexanoate355162 isopropyl (S)-6-diazo-2-(4-methoxy-1-methylpiperidine-4-carboxamido)-5-oxohexanoate369163 isopropyl (2S)-6-diazo-5-oxo-2-(tetrahydrofuran-2-carboxamido)hexan oate312164 isopropyl (2S)-6-diazo-5-oxo-2-(tetrahydro-2H-pyran-2-carboxamido)hexan oate326165 isopropyl (2S)-6-diazo-2-(hexahydro-1H-cyclopenta[c]furan-1-carboxamido)-5-oxohexanoate352166 isopropyl (S)-2-(2-(cyclopropylmetho xy)acetamido)-6-diazo-5-oxohexanoateMS: 326(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 5.02 (dt, J = 12.5, 6.3 Hz, 1H), 4.44 (dd, J = 8.8, 5.0 Hz, 1H), 4.09 - 3.89 (m, 2H), 3.40 (d, J = 6.9 Hz, 2H), 2.45 (s, 2H), 2.11 (ddq, J = 37.1, 14.6, 7.3 Hz, 2H), 1.34 - 1.20 (m, 6H), 1.12 (tt, J = 12.4, 6.2 Hz, 1H), 0.56 (d, J = 8.0 Hz, 2H), 0.26 (d, J = 3.7 Hz, 2H).167 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-phenylpropanamido )-5-oxohexanoateMS: 362(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.62 - 7.56 (m, 2H), 7.35 - 7.28 (m, 2H), 7.28 - 7.22 (m, 1H), 4.93 (dt, J = 12.5, 6.3 Hz, 1H), 4.31 (dd, J = 8.9, 5.1 Hz, 1H), 2.42 (s, 2H), 2.29 - 1.94 (m, 2H), 1.75 (s, 3H), 1.13 (dd, J = 19.5, 6.3 Hz, 6H).168 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-phenylpropanamido )-5-oxohexanoateMS: 362(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.63 - 7.58 (m, 2H), 7.37 - 7.30 (m, 2H), 7.28 - 7.23 (m, 1H), 5.01 (dt, J = 12.5, 6.3 Hz, 1H), 4.29 (dd, J = 9.2, 4.5 Hz, 1H), 2.29 - 2.09 (m, 3H), 1.99 - 1.87 (m, 1H), 1.73 (s, 3H), 1.24 (dd, J = 6.2, 3.2 Hz, 5H).169 isopropyl (S)-2-((S)-2-(2-cyanoacetoxy)-3-(7-fluoro-1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoateMS: 486(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.47 - 7.35 (m, 1H), 7.24 - 7.13 (m, 1H), 6.93 (td,J = 7.8, 4.0 Hz, 1H), 6.84 - 6.72 (m, 1H), 5.36 (s, 1H), 5.07 - 4.91 (m, 1H), 4.43 - 4.32 (m, 1H), 4.43 - 4.19 (m, 2H), 4.32 - 4.19 (m, 1H), 3.23 - 3.09 (m, 2H), 2.12 - 1.60 (m, 4H), 1.27 - 1.13 (m, 6H).170 isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-(isobutyryloxy)pro panamido)-5-oxohexanoate489171 1-methylpiperidin-4-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate355172 isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydrofuran-2-carboxamido)hexan oateMS: 312(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.83 (s, 1H), 5.01 (dt,J = 12.6, 6.2 Hz, 1H), 4.38 - 4.27 (m, 2H), 4.07 - 3.97 (m, 1H), 3.93 - 3.82 (m, 1H), 2.43 (s, 2H), 2.31 - 2.12 (m, 2H), 2.07 - 1.83 (m, 4H), 1.29 - 1.23 (m, 6H).173 isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydro-2H-pyran-2-carboxamido)hexan oate326174 isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydrofuran-3-carboxamido)hexan oateMS: 312(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 5.00 (dt, J = 12.5, 6.2 Hz, 1H), 4.32 (dd, J = 9.1, 5.2 Hz, 1H), 3.97 - 3.90 (m, 1H), 3.91 - 3.74 (m, 3H), 3.14 - 3.03 (m, 1H), 2.44 (s, 2H), 2.22 - 2.06 (m, 3H), 2.00 - 1.88 (m, 1H), 1.25 (dd, J = 6.2, 4.1 Hz, 6H).175 isopropyl (S)-6-diazo-5-oxo-2-((S)-tetrahydro-2H-pyran-3-carboxamido)hexan oate326176 isopropyl (S)-6-diazo-2-(3-methoxy-2-oxopropanamido)-5-oxohexanoate314177 isopropyl (S)-6-diazo-2-(3-hydroxy-2-oxopropanamido)-5-oxohexanoate300178 cyclobutyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoateMS: 312(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 5.04 - 4.91 (m, 1H), 4.49 - 4.29 (m, 1H), 3.76 (p, J = 6.8 Hz, 1H), 3.44 - 3.34 (m, 3H), 2.51 - 2.29 (m, 4H), 2.25 - 1.98 (m, 4H), 1.88 - 1.76 (m, 1H), 1.73 - 1.62 (m, 1H), 1.33 (d, J = 6.8 Hz, 3H).179 cyclopentyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoateMS: 326(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.27 - 5.07 (m, 1H), 4.43 - 4.30 (m, 1H), 3.76 (p, J = 6.6 Hz, 1H), 3.46 - 3.34 (m, 3H), 2.57 - 2.34 (m, 2H), 2.26 - 2.12 (m, 1H), 2.06 - 1.93 (m, 1H), 1.94 - 1.82 (m, 2H), 1.81- 1.56 (m, 6H), 1.34 (d,J = 6.8 Hz, 3H).180 2-(pyrrolidin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate355181 (pivaloyloxy)methy l (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate372182 isopentyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoateMS: 328(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 4.48 - 4.36 (m, 1H), 4.17 (dt, J = 6.6, 4.3 Hz, 2H), 3.76 (p, J = 6.8 Hz, 1H), 3.45 - 3.33 (m, 3H), 2.51 - 2.37 (m, 2H), 2.28 - 2.15 (m, 1H), 2.07 - 1.93 (m, 1H), 1.71 (dt,J = 13.4, 6.7 Hz, 1H), 1.62 - 1.49 (m, 2H), 1.37 - 1.29 (m, 3H), 0.93 (d, J = 6.6 Hz, 6H).183 isopropyl (S)-6-diazo-2-(3-hydroxypropanami do)-5-oxohexanoateMS: 286(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.00 (dt, J = 12.7, 6.5 Hz, 1H), 4.37 (dd, J = 9.0, 5.1 Hz, 1H), 3.81 (dd, J = 10.2, 5.3 Hz, 2H), 2.55 - 2.37 (m, 4H), 2.22 - 2.08 (m, 1H), 1.99 - 1.83 (m, 1H), 1.37 - 1.17 (m, 6H).184 isopropyl (S)-6-diazo-2-((S)-3-hydroxybutanamid o)-5-oxohexanoateMS: 286(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.00 (dt, J = 12.5, 6.2 Hz, 1H), 4.35 (dd, J = 8.6, 5.2 Hz, 1H), 4.14 (dd, J = 12.6, 6.3 Hz, 1H), 2.50 - 2.28 (m, 4H), 2.15 (td, J = 13.6, 6.9 Hz, 1H), 1.93 (td, J = 15.2, 7.9 Hz, 1H), 1.25 (d, J = 6.2 Hz, 6H), 1.21 (d, J = 6.1 Hz, 3H).185 isopropyl (S)-6-diazo-2-(3-methoxypropanami do)-5-oxohexanoateMS: 300(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.00 (dt, J = 12.4, 6.2 Hz, 1H), 4.36 (dd, J = 8.9, 5.1 Hz, 1H), 3.70 - 3.55 (m, 2H), 3.33 (s, 3H), 2.58 - 2.35 (m, 4H), 2.14 (td, J = 13.5, 7.2 Hz, 1H), 1.91 (td, J = 15.1, 7.8 Hz, 1H), 1.30 - 1.20 (m, 6H).186 isopropyl (S)-6-diazo-2-((S)-3-methoxybutanamid o)-5-oxohexanoate314187 isopropyl (S)-6-diazo-2-((S)-3-hydroxy-2-methylpropanamid o)-5-oxohexanoateMS: 300(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 5.00 (dt, J = 12.4, 6.3 Hz, 1H), 4.34 (dd, J = 8.7, 5.1 Hz, 1H), 3.73 - 3.63 (m, 1H), 3.56 - 3.45 (m, 1H), 2.56 (dd, J = 13.6, 6.7 Hz, 1H), 2.44 (s, 2H), 2.22 - 2.08 (m, 1H), 2.02 - 1.88 (m, 1H), 1.25 (d, J = 6.2 Hz, 6H), 1.11 (d, J = 6.9 Hz, 3H).188 isopropyl (S)-6-diazo-2-((S)-3-methoxy-2-methylpropanamid o)-5-oxohexanoateMS: 314(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 5.00 (dt, J = 12.5, 6.3 Hz, 1H), 4.33 (dd, J = 9.0, 5.2 Hz, 1H), 3.53 (dd, J = 9.3, 8.1 Hz, 1H), 3.38 - 3.33 (m, 1H), 3.33 (s, 3H), 2.68 (dd, J = 13.4, 7.1 Hz, 1H), 2.43 (s, 2H), 2.25 - 2.08 (m, 1H), 2.02 - 1.86 (m, 1H), 1.25 (dd, J = 6.2, 2.7 Hz, 6H), 1.10 (d, J = 7.0 Hz, 3H).189 isopropyl (S)-6-diazo-2-((S)-oxetane-2-carboxamido)-5-oxohexanoateMS: 298(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 5.12 - 4.98 (m, 2H), 4.83 - 4.64 (m, 2H), 4.45 (dd, J = 9.2, 4.9 Hz, 1H), 3.11 - 2.95 (m, 1H), 2.70 - 2.55 (m, 1H), 2.45 (s, 2H), 2.30 - 2.18 (m, 1H), 2.10 - 1.94 (m, 1H), 1.31 - 1.27 (m, 6H).190 isopropyl (S)-6-diazo-2-((2S,3R)-3-hydroxy-2-methylbutanamido) -5-oxohexanoate314191 isopropyl (S)-6-diazo-2-((2S,3R)-3-methoxy-2-methylbutanamido) -5-oxohexanoate328192 isopropyl (S)-6-diazo-2-((2R,3R)-3-hydroxy-2-methylbutanamido) -5-oxohexanoate314193 isopropyl (S)-6-diazo-2-((2R,3R)-3-methoxy-2-methylbutanamido) -5-oxohexanoate328194 isopropyl (S)-6-diazo-2-((2R,3S)-3-hydroxy-2-methylbutanamido) -5-oxohexanoate314195 isopropyl (S)-6-diazo-2-((2R,3S)-3-methoxy-2-methylbutanamido) -5-oxohexanoate328196 isopropyl (S)-6-diazo-2-((R)-3-hydroxybutanamid o)-5-oxohexanoate300197 isopropyl (S)-6-diazo-2-((2S,3S)-3-hydroxy-2-methylbutanamido) -5-oxohexanoate314198 isopropyl (S)-6-diazo-2-((2S,3S)-3-methoxy-2-methylbutanamido) -5-oxohexanoate328199 isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydrofuran-2-carboxamido)hexan oate312200 isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydro-2H-pyran-2-carboxamido)hexan oate326201 isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydrofuran-3-carboxamido)hexan oateMS: 312(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 4.99 (dt, J = 12.5, 6.2 Hz, 1H), 4.32 (dd, J = 9.1, 5.2 Hz, 1H), 3.99 - 3.93 (m, 1H), 3.91 - 3.84 (m, 1H), 3.83 - 3.74 (m, 2H), 3.14 - 2.98 (m, 1H), 2.45 (s, 2H), 2.21 - 2.06 (m, 3H), 1.93 (dt, J = 14.4, 7.5 Hz, 1H), 1.24 (dd, J = 6.2, 4.3 Hz, 6H).202 isopropyl (S)-6-diazo-5-oxo-2-((R)-tetrahydro-2H-pyran-3-carboxamido)hexan oate326203 isopropyl (S)-6-diazo-2-((R)-3-methoxybutanamid o)-5-oxohexanoate314204 isopropyl (S)-6-diazo-5-oxo-2-((R)-3,3,3-trifluoro-2-methoxypropanami do)hexanoate354205 isopropyl (S)-6-diazo-5-oxo-2-((R)-3,3,3-trifluoro-2-hydroxypropanami do)hexanoate340206 isopropyl (S)-6-diazo-5-oxo-2-((S)-3,3,3-trifluoro-2-methoxypropanami do)hexanoate354207 isopropyl (S)-6-diazo-5-oxo-2-((S)-3,3,3-trifluoro-2-hydroxypropanami do)hexanoate340208 isopropyl (S)-6-diazo-2-((R)-oxetane-2-carboxamido)-5-oxohexanoateMS: 298(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.85 (s, 1H), 5.09 - 4.96 (m, 2H), 4.80 - 4.60 (m, 2H), 4.43 (dd, J = 9.0, 5.0 Hz, 1H), 3.11 - 2.97 (m, 1H), 2.70 - 2.56 (m, 1H), 2.50 (s, 2H), 2.35 - 2.19 (m, 1H), 2.17 - 1.99 (m, 1H), 1.26 (d, J = 6.3 Hz, 6H).209 isopropyl (S)-6-diazo-2-(oxetane-3-carboxamido)-5-oxohexanoate298210 isopropyl (S)-6-diazo-2-((R)-3-hydroxy-2-methylpropanamid o)-5-oxohexanoate300211 isopropyl (S)-6-diazo-5-oxo-2-(tetrahydro-2H-pyran-4-carboxamido)hexan oate326212 isopropyl (2S)-6-diazo-5-oxo-2-((1S)-tetrahydro-1H,3H-furo[3,4-c]furan-1-carboxamido)hexan oate354213 isopropyl (2S)-6-diazo-5-oxo-2-((1R)-tetrahydro-1H,3H-furo[3,4-c]furan-1-carboxamido)hexan oate354214 isopropyl (S)-2-((S)-2-cyano-2-hydroxyacetamido) -6-diazo-5-oxohexanoate297215 isopropyl (S)-2-((S)-2-cyano-2-methoxyacetamido) -6-diazo-5-oxohexanoate311216 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-oxobutanamido)-5-oxohexanoate328217 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-oxobutanamido)-5-oxohexanoate314218 isopropyl (S)-6-diazo-2-((R)-3-methoxy-2-methylpropanamid o)-5-oxohexanoateMS: 298(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.78 (s, 1H), 5.00 (dt, J = 12.5, 6.3 Hz, 1H), 4.36 (dd, J = 9.5, 4.9 Hz, 1H), 3.52 (t, J = 9.1 Hz, 1H), 3.35 - 3.32 (m, 4H), 2.74 - 2.59 (m, 1H), 2.45 (s, 2H), 2.23 - 2.08 (m, 1H), 1.98 - 1.82 (m, 1H), 1.25 (dd, J = 6.1, 4.7 Hz, 6H), 1.08 (d, J = 7.0 Hz, 3H).219 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate367220 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate355221 isopropyl (S)-2-((R)-2-cyano-2-hydroxyacetamido) -6-diazo-5-oxohexanoate297222 isopropyl (S)-2-((R)-2-cyano-2-methoxyacetamido) -6-diazo-5-oxohexanoate311223 isopropyl (S)-6-diazo-2-((R)-2-methoxy-3-oxobutanamido)-5-oxohexanoate328224 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-3-oxobutanamido)-5-oxohexanoate314225 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate369226 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiazol-4-yl)acetamido)-5-oxohexanoate355227 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate351228 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate351229 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate337230 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate337231 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate353232 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate339233 isopropyl (S)-6-diazo-2-((S)-2-(furan-2-yl)-2-methoxyacetamido) -5-oxohexanoate352234 isopropyl (S)-6-diazo-2-((S)-2-(furan-3-yl)-2-methoxyacetamido) -5-oxohexanoate352235 isopropyl (S)-6-diazo-2-((S)-2-(furan-2-yl)-2-hydroxyacetamido) -5-oxohexanoate338236 isopropyl (S)-6-diazo-2-((S)-2-(furan-3-yl)-2-hydroxyacetamido) -5-oxohexanoate338237 isopropyl (S)-2-((S)-2-(1H-imidazol-4-yl)-2-methoxyacetamido) -6-diazo-5-oxohexanoate352238 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-imidazol-4-yl)acetamido)-5-oxohexanoate338239 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate351240 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate351241 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-pyrrol-2-yl)acetamido)-5-oxohexanoate337242 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-pyrrol-3-yl)acetamido)-5-oxohexanoate337243 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate353244 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(oxazol-4-yl)acetamido)-5-oxohexanoate339245 isopropyl (S)-6-diazo-2-((R)-2-(furan-2-yl)-2-methoxyacetamido) -5-oxohexanoate352246 isopropyl (S)-6-diazo-2-((R)-2-(furan-3-yl)-2-methoxyacetamido) -5-oxohexanoate352247 isopropyl (S)-6-diazo-2-((R)-2-(furan-2-yl)-2-hydroxyacetamido) -5-oxohexanoate338248 isopropyl (S)-6-diazo-2-((R)-2-(furan-3-yl)-2-hydroxyacetamido) -5-oxohexanoate338249 isopropyl (S)-2-((R)-2-(1H-imidazol-4-yl)-2-methoxyacetamido) -6-diazo-5-oxohexanoate352250 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-imidazol-4-yl)acetamido)-5-oxohexanoate338251 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate368252 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate368253 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate354254 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate354255 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate369256 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate355257 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-5-oxohexanoate366258 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-5-oxohexanoate352259 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate366260 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate352261 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate353262 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate339263 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate366264 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1-methyl-1H-imidazol-4-yl)acetamido)-5-oxohexanoate352265 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate353266 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(oxazol-2-yl)acetamido)-5-oxohexanoate339267 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate368268 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate368269 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiophen-2-yl)acetamido)-5-oxohexanoate354270 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiophen-3-yl)acetamido)-5-oxohexanoate354271 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate369272 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(thiazol-2-yl)acetamido)-5-oxohexanoate355273 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-5-oxohexanoate366274 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1-methyl-1H-imidazol-2-yl)acetamido)-5-oxohexanoate352275 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(thiazol-5-yl)acetamido)-5-oxohexanoate369276 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(thiazol-5-yl)acetamido)-5-oxohexanoate355277 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(1-methyl-1H-imidazol-5-yl)acetamido)-5-oxohexanoate366278 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1-methyl-1H-imidazol-5-yl)acetamido)-5-oxohexanoate352279 isopropyl (S)-2-((R)-2-(1H-imidazol-2-yl)-2-methoxyacetamido) -6-diazo-5-oxohexanoate352280 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-imidazol-2-yl)acetamido)-5-oxohexanoate338281 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(oxazol-5-yl)acetamido)-5-oxohexanoate353282 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(oxazol-5-yl)acetamido)-5-oxohexanoate339283 isopropyl (S)-2-((S)-2-(1H-imidazol-5-yl)-2-methoxyacetamido) -6-diazo-5-oxohexanoate352284 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(1H-imidazol-5-yl)acetamido)-5-oxohexanoate338285 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate363286 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate349287 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate364288 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate350289 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate364290 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate350291 isopropyl (S)-6-diazo-2-((S)-2-(3-fluoropyridin-4-yl)-2-methoxyacetamido) -5-oxohexanoate381292 isopropyl (S)-6-diazo-2-((S)-2-(3-fluoropyridin-4-yl)-2-hydroxyacetamido) -5-oxohexanoate367293 isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-2-yl)-2-methoxyacetamido) -5-oxohexanoate381294 isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-2-yl)-2-hydroxyacetamido) -5-oxohexanoate367295 isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-3-yl)-2-methoxyacetamido) -5-oxohexanoate381296 isopropyl (S)-6-diazo-2-((S)-2-(5-fluoropyridin-3-yl)-2-hydroxyacetamido) -5-oxohexanoate367297 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(3-methoxypyridin-4-yl)acetamido)-5-oxohexanoate393298 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(3-methoxypyridin-4-yl)acetamido)-5-oxohexanoate379299 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(5-methoxypyridin-2-yl)acetamido)-5-oxohexanoate393300 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(5-methoxypyridin-2-yl)acetamido)-5-oxohexanoate379301 isopropyl (S)-6-diazo-2-((S)-2-methoxy-2-(5-methoxypyridin-3-yl)acetamido)-5-oxohexanoate393302 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-2-(5-methoxypyridin-3-yl)acetamido)-5-oxohexanoate379303 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(5-methoxypyridin-2-yl)acetamido)-5-oxohexanoate393304 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(5-methoxypyridin-2-yl)acetamido)-5-oxohexanoate379305 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(5-methoxypyridin-3-yl)acetamido)-5-oxohexanoate393306 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(5-methoxypyridin-3-yl)acetamido)-5-oxohexanoate379307 isopropyl (S)-2-((R)-2-(1H-imidazol-5-yl)-2-methoxyacetamido) -6-diazo-5-oxohexanoate352308 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(1H-imidazol-5-yl)acetamido)-5-oxohexanoate338309 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate363310 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(pyridin-2-yl)acetamido)-5-oxohexanoate349311 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate364312 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(pyrimidin-4-yl)acetamido)-5-oxohexanoate350313 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate364314 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(pyrimidin-2-yl)acetamido)-5-oxohexanoate350315 isopropyl (S)-6-diazo-2-((R)-2-(3-fluoropyridin-4-yl)-2-methoxyacetamido) -5-oxohexanoate381316 isopropyl (S)-6-diazo-2-((R)-2-(3-fluoropyridin-4-yl)-2-hydroxyacetamido) -5-oxohexanoate367317 isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-2-yl)-2-methoxyacetamido) -5-oxohexanoate381318 isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-2-yl)-2-hydroxyacetamido) -5-oxohexanoate367319 isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-3-yl)-2-methoxyacetamido) -5-oxohexanoate381320 isopropyl (S)-6-diazo-2-((R)-2-(5-fluoropyridin-3-yl)-2-hydroxyacetamido) -5-oxohexanoate367321 isopropyl (S)-6-diazo-2-((R)-2-methoxy-2-(3-methoxypyridin-4-yl)acetamido)-5-oxohexanoate393322 isopropyl (S)-6-diazo-2-((R)-2-hydroxy-2-(3-methoxypyridin-4-yl)acetamido)-5-oxohexanoate379323 tert-butyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate314324 phenyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate334325 benzyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate348326 cyclohexyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate340327 cycloheptyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate354328 cyclooctyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate368329 cyclooctyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate368330 tert-butyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate314331 phenyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate334332 benzyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate348333 cyclohexyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate340334 cycloheptyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate354335 1-methylpiperidin-4-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate355336 pyridin-4-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate335337 pyridin-4-ylmethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate349338 tetrahydro-2H-pyran-4-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate342339 1-methylpiperidin-4-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate355340 (R)-oxepan-4-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate356341 (S)-oxepan-4-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate356342 oxocan-5-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate370343 pyridin-4-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate335344 pyridin-4-ylmethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate349345 tetrahydro-2H-pyran-4-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate342346 1-methylpiperidin-4-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate355347 (R)-oxepan-4-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate356348 (S)-oxepan-4-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate356349 oxocan-5-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate370350 trifluoromethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate326351 2,2,2-trifluoroethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate340352 (S)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate354353 3,3,3-trifluoropropyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate354354 (S)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate368355 1,1,1-trifluoro-2-methylpropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate368356 4,4,4-trifluoro-2-methylbutan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate382357 cyanic (S)-6-diazo-2-((S)-2-methoxypropanami do)-5 -oxohexanoic anhydride283358 cyanomethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate297359 (S)-1-cyanoethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate311360 2-cyanoethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate311361 1-cyanopropan-2-yl (2S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate325362 2-cyanopropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate325363 1-cyano-2-methylpropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate339364 hydroxymethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate288365 methoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate302366 ethoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate316367 isopropoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate330368 cyclopropoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate328369 cyclobutoxymethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate342370 trifluoromethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate326371 2,2,2-trifluoroethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate340372 (S)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate354373 (R)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate354374 (R)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate368375 (R)-1-cyanoethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate311376 (R)-1-cyanopropan-2-yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate325377 (R)-1,1,1-trifluoropropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate354378 3,3,3-trifluoropropyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate354379 (S)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate368380 (R)-4,4,4-trifluorobutan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate368381 1,1,1-trifluoro-2-methylpropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate368382 4,4,4-trifluoro-2-methylbutan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate382383 cyanic (S)-6-diazo-2-((R)-2-methoxypropanami do)-5 -oxohexanoic anhydride283384 cyanomethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate297385 (S)-1-cyanoethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate311386 (R)-1-cyanoethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate311387 2-cyanoethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate311388 (S)-1-cyanopropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate325389 (R)-1-cyanopropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate325390 2-cyanopropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate325391 1-cyano-2-methylpropan-2-yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate339392 hydroxymethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate288393 methoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate302394 ethoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate316395 isopropoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate330396 cyclopropoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate328397 cyclobutoxymethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate342398 2-(pyrrolidin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate355399 2-methoxyethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate316400 2-ethoxyethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate330401 2-isopropoxyethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate344402 2-aminoethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate301403 2-(methylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate315404 2-(dimethylamino)eth yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate329405 2-(ethylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate329406 2-(isopropylamino)et hyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate343407 2-(cyclopropylamino) ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate341408 2-(cyclobutylamino)e thyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate355409 2-(cyclopentylamino) ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate369410 2-(cyclohexylamino)e thyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate383411 2-(azetidin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate341412 2-(piperidin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate369413 2-(azepan-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate383414 2-(azocan-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate397415 2-morpholinoethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate371416 2-(phenylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate377417 2-(pyridin-4-ylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate378418 2-(benzylamino)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate391419 2-((pyridin-4-ylmethyl)amino)eth yl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate392420 2-(4-methylpiperazin-1-yl)ethyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate384421 2-methoxyethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate316422 2-ethoxyethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate330423 2-isopropoxyethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate344424 2-aminoethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate301425 2-(methylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate315426 2-(dimethylamino)eth yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate329427 2-(ethylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate329428 2-(isopropylamino)et hyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate343429 2-(cyclopropylamino) ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate341430 2-(cyclobutylamino)e thyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate355431 2-(cyclopentylamino) ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate369432 2-(cyclohexylamino)e thyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate383433 2-(azetidin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate341434 2-(piperidin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate369435 2-(azepan-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate383436 2-(azocan-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate397437 2-morpholinoethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate371438 2-(phenylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate377439 2-(pyridin-4-ylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate378440 2-(benzylamino)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate391441 2-((pyridin-4-ylmethyl)amino)eth yl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate392442 2-(4-methylpiperazin-1-yl)ethyl (S)-6-diazo-2-((R)-2-methoxypropanami do)-5-oxohexanoate384443 isopropyl (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butana mido)-5-oxohexanoateMS: 360(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 7.23 - 7.04 (m, 1H), 5.26 (s, 1H), 5.11 - 4.95 (m, 1H), 4.58 - 4.44 (m, 1H), 3.86 - 3.68 (m, 1H), 3.50 - 3.35 (m, 3H), 2.64 - 2.50 (m, 2H), 2.40 (s, 2H), 2.26 - 2.15 (m, 1H), 2.10 - 2.05 (m, 3H), 2.06 - 1.86 (m, 3H), 1.29 - 1.19 (m, 6H).444 isopropyl (S)-6-diazo-2-(2-hydroxy-2-methylpropanamid o)-5-oxohexanoateMS: 300(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 5.01 (dt, J = 12.5, 6.3 Hz, 1H), 4.33 (dd, J = 8.7, 5.1 Hz, 1H), 2.43 (s, 2H), 2.29 - 2.11 (m, 1H), 2.10 - 1.90 (m, 1H), 1.36 (d, J = 3.3 Hz, 6H), 1.26 (dd, J = 6.2, 2.9 Hz, 6H).445 methyl (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butana mido)-5-oxohexanoate332446 methyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoateMS: 373(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.61 (d, J = 7.9 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.14 (s, 1H), 7.11 - 7.03 (m, 1H), 7.03 - 6.94 (m, 1H), 5.23 (s, 1H), 4.38 (t, J = 4.9 Hz, 1H), 4.32 - 4.22 (m, 1H), 3.67 (s, 3H), 3.25 - 3.12 (m, 2H), 1.96 - 1.84 (m, 1H), 1.81 - 1.60 (m, 3H).447 methyl (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido) -5-oxohexanoateMS: 286(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 4.46 (dd, J = 8.5, 5.1 Hz, 1H), 3.87 (d, J = 3.4 Hz, 1H), 3.73 (s, 3H), 2.54 - 2.33 (m, 2H), 2.29 - 2.14 (m, 1H), 2.15 - 1.92 (m, 2H), 1.01 (d, J = 6.9 Hz, 3H), 0.87 (d, J = 6.8 Hz, 3H).448 methyl (S)-6-diazo-2-(2-isopropoxyacetami do)-5-oxohexanoateMS: 286(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 4.50 (dd, J = 8.7, 5.0 Hz, 1H), 4.05 - 3.88 (m, 2H), 3.74 (s, 3H), 3.72 - 3.66 (m, 1H), 2.45 (s, 2H), 2.31 - 2.15 (m, 1H), 2.13 - 1.92 (m, 1H), 1.30 - 1.15 (m, 6H).449 (S)-6-diazo-2-((S)-2-hydroxypropanami do)-5 -oxohexanoic acid244450 cyclopropyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoateMS: 298(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 4.44 - 4.29 (m, 1H), 4.15 (dt, J = 8.8, 2.8 Hz, 1H), 3.82 - 3.70 (m, 1H), 3.42 - 3.34 (m, 3H), 2.44 (s, 2H), 2.28 - 2.10 (m, 1H), 2.06 - 1.91 (m, 1H), 1.35 - 1.31 (m, 3H), 0.78 - 0.63 (m, 4H).451 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-methoxypropanami do)-6-diazo-5-oxohexanoateMS: 415(M+H) +< , 1< H NMR (400 MHz, CDCl 3 ) δ 8.12 - 8.00 (m, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 7.17 - 7.05 (m, 3H), 6.92 - 6.83 (m, 1H), 4.96 (dt, J = 12.6, 6.3 Hz, 1H), 4.76 (s, 1H), 4.46 - 4.34 (m, 1H), 4.00 - 3.92 (m, 1H), 3.50 - 3.41 (m, 3H), 3.29 - 3.19 (m, 2H), 1.94 - 1.69 (m, 2H), 1.70 - 1.59 (m, 2H), 1.21 - 1.16 (m, 6H).452 isopropyl (S)-6-diazo-2-(2-isopropoxyacetami do)-5-oxohexanoateMS: 314(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 5.02 (dt, J = 12.5, 6.3 Hz, 1H), 4.42 (dd, J = 8.7, 5.0 Hz, 1H), 4.03 - 3.87 (m, 2H), 3.70 (dt, J = 12.2, 6.1 Hz, 1H), 2.44 (s, 2H), 2.27 - 2.14 (m, 1H), 2.10 - 1.93 (m, 1H), 1.26 (dd, J = 6.3, 2.1 Hz, 6H), 1.22 (dd, J = 6.1, 3.4 Hz, 6H).453 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoateMS: 429(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.57 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.15 (t, J = 7.1 Hz, 1H), 7.08 - 6.99 (m, 2H), 5.26 (s, 1H), 4.26 - 4.18 (m, 1H), 3.96 (t, J = 5.0 Hz, 1H), 3.75 (s, 3H), 3.48 (s, 3H), 3.22 - 3.16 (m, 2H), 1.95 - 1.83 (m, 1H), 1.80 - 1.61 (m, 3H), 1.22 (dd, J = 8.6, 6.3 Hz, 6H).454 isopropyl (S)-6-diazo-2-((R)-2-methoxy-3-(1-methyl-1H-indol-3-yl)propanamido)-5-oxohexanoateMS: 429(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.55 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.2 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 7.06 - 6.99 (m, 2H), 5.49 (s, 1H), 4.94 (dt, J = 12.5, 6.2 Hz, 1H), 4.21 - 4.09 (m, 1H), 3.94 (t, J = 6.4 Hz, 1H), 3.74 (s, 3H), 3.37 (s, 3H), 3.13 (ddd, J = 34.8, 14.5, 6.4 Hz, 2H), 2.06 - 1.85 (m, 3H), 1.82 - 1.69 (m, 1H), 1.20 (dd, J = 8.8, 6.3 Hz, 6H).456 methyl (S)-6-diazo-2-((S)-2-hydroxy-2-phenylacetamido)-5-oxohexanoateMS: 320(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.53 - 7.43 (m, 2H), 7.42 - 7.22 (m, 3H), 5.05 (s, 1H), 4.45 (dd, J = 8.9, 4.8 Hz, 1H), 3.71 (s, 3H), 2.33 (s, 2H), 2.27 - 2.12 (m, 1H), 2.07 - 1.91 (m, 1H).457 methyl (S)-6-diazo-2-((S)-2-methoxy-2-phenylacetamido)-5-oxohexanoateMS: 334(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 7.47 - 7.42 (m, 2H), 7.40 - 7.32 (m, 3H), 5.57 (s, 1H), 4.68 (s, 1H), 4.44 (dd, J = 9.4, 4.8 Hz, 1H), 3.71 (s, 3H), 3.42 (s, 3H), 2.32 (s, 2H), 2.26 - 2.12 (m, 1H), 2.05 - 1.97 (m, 1H).458 methyl (S)-6-diazo-2-(2-methoxyacetamido) -5-oxohexanoateMS: 258(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.82 (s, 1H), 4.50 (dd, J = 8.8, 5.0 Hz, 1H), 3.93 (d, J = 4.0 Hz, 2H), 3.73 (s, 3H), 3.43 (s, 3H), 2.44 (s, 2H), 2.30 - 2.16 (m, 1H), 2.11 - 1.93 (m, 1H).459 S-isopropyl (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanethioateMS: 316(M+H) +< , 1< H NMR (400 MHz, CD 3 OD) δ 5.81 (s, 1H), 4.51 (dd, J = 9.9, 4.6 Hz, 1H), 3.80 (q, J = 6.7 Hz, 1H), 3.59 (dt, J = 13.7, 6.9 Hz, 1H), 3.44 (s, 3H), 2.43 (s, 2H), 2.31 - 2.16 (m, 1H), 2.04 - 1.87 (m, 1H), 1.35 (d, J = 6.8 Hz, 3H), 1.30 (d, J = 6.9 Hz, 6H).460 (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butana mido)-5-oxohexanoic acid318461 isopropyl (2S)-2-(2-acetoxy-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate442462 isopropyl (2S)-2-(2-(2-cyanoacetoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate467463 isopropyl (2S)-6-diazo-2-(2-((dimethylglycyl)o xy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate486464 isopropyl (2S)-2-(3-(1H-indol-3-yl)-2-(2-(2-oxopyrrolidin-1-yl)acetoxy)propana mido)-6-diazo-5-oxohexanoate526465 isopropyl (2S)-6-diazo-2-(2-hydroxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate400466 isopropyl (S)-6-diazo-2-((S)-2-(2-hydroxyethoxy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate444467 isopropyl (S)-2-((S)-2-(2-acetamidoethoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate486468 isopropyl (S)-2-((S)-2-(2-cyanoethoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate454469 isopropyl (S)-2-((S)-2-(cyanomethoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate439470 isopropyl (S)-6-diazo-2-((S)-2-(2-(dimethylamino)-2-oxoethoxy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate486471 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(2-(methylamino)-2-oxoethoxy)propana mido)-6-diazo-5-oxohexanoate472472 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(2-oxopropoxy)propan amido)-6-diazo-5-oxohexanoate457473 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-((tetrahydro-2H-pyran-4-yl)oxy)propanamid o)-6-diazo-5-oxohexanoate485474 isopropyl (S)-2-((S)-2-(3-amino-3-oxopropoxy)-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate472475 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(3-(methylamino)-3-oxopropoxy)propan amido)-6-diazo-5-oxohexanoate486476 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate428477 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1H-pyrrolo[3,2-b]pyridin-3-yl)propanamido)-5-oxohexanoate415478 isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanamido)-5-oxohexanoate415479 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)propanamido)-5-oxohexanoate415480 isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamido)-5-oxohexanoate415481 isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-(7-fluoro-1H-indol-3-yl)propanamido)-5-oxohexanoate447482 isopropyl (S)-6-diazo-2-((S)-3-(7-fluoro-1H-indol-3-yl)-2-isopropoxypropana mido)-5-oxohexanoate461483 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-phenoxypropanami do)-6-diazo-5-oxohexanoate477484 isopropyl (2S)-2-(3-(1H-indol-3-yl)-2-((methylglycyl)oxy )propanamido)-6-diazo-5-oxohexanoate472485 isopropyl (2S)-6-diazo-2-(2-(glycyloxy)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate457486 isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate303487 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoic acid261488 methyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate275489 ethyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate289490 S-isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate319491 isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butana mido)-5-oxohexanoate363492 methyl-d3 (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate275493 ethyl-2,2,2-d3 (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate289494 isopropyl (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate303495 isopropyl (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate305496 ethyl-d5 (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate291497 propan-2-yl-d7 (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate307498 propan-2-yl-d7 (S)-6-diazo-2-((S)-2-hydroxypropanami do)-5-oxohexanoate293499 propan-2-yl-d7 (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido) -5-oxohexanoate321500 propan-2-yl-d7 (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate307501 S-(propan-2-yl-d7) (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanethioate323502 propan-2-yl-d7 (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butana mido)-5-oxohexanoate367503 methyl-d3 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate278504 ethyl-2,2,2-d3 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate292505 ethyl-d5 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate294506 propan-2-yl-d7 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate310507 propan-2-yl-d7 (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate310508 S-(propan-2-yl-d7) (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate326509 propan-2-yl-d7 (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butana mido)-5-oxohexanoate370510 propan-2-yl-d7 (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate312511 methyl 6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate-2-d273512 ethyl 6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate-2-d287513 isopropyl 6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate-2-d301514 isopropyl 6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate-2-d301515 S-isopropyl 6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanethioate-2-d317516 isopropyl 6-diazo-2-((S)-2-methoxy-4-(methylthio)butana mido)-5-oxohexanoate-2-d361517 isopropyl 6-diazo-2-((S)-2-hydroxypropanami do)-5-oxohexanoate-2-d287518 isopropyl 6-diazo-2-((S)-2-hydroxy-3-methylbutanamido) -5-oxohexanoate-2-d315519 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate309520 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate309521 S-(propan-2-yl-1,1,1,3,3,3-d6) (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate325522 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butana mido)-5-oxohexanoate369523 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate311524 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-hydroxypropanami do)-5-oxohexanoate292525 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido) -5-oxohexanoate320526 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate306527 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate306528 S-(propan-2-yl-1,1,1-d3) (2S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate322529 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butana mido)-5-oxohexanoate366530 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate308531 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-hydroxypropanami do)-5-oxohexanoate289532 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido) -5-oxohexanoate317533 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate306534 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate306535 S-(propan-2-yl-1,1,1,3,3,3-d6) (S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanethioate322536 propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butana mido)-5-oxohexanoate366537 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanoate303538 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate303539 S-(propan-2-yl-1,1,1-d3) (2S)-6-diazo-2-((S)-2-methoxypropanami do)-5-oxohexanethioate319540 propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butana mido)-5-oxohexanoate363541 methyl (S)-6-diazo-2-((S)-2-(methylthio)propan amido)-5-oxohexanoate288542 ethyl (S)-6-diazo-2-((S)-2-(methylthio)propan amido)-5-oxohexanoate302543 isopropyl (S)-6-diazo-2-((S)-2-(methylthio)propan amido)-5-oxohexanoate316544 isopropyl (S)-6-diazo-2-((S)-2-mercaptopropanami do)-5-oxohexanoate302545 isopropyl (S)-6-diazo-2-((S)-2-mercapto-3-methylbutanamido) -5-oxohexanoate330546 isopropyl (S)-6-diazo-2-(2-(ethylthio)acetamid o)-5-oxohexanoate316547 S-isopropyl (S)-6-diazo-2-((S)-2-(methylthio)propan amido)-5-oxohexanethioate332548 isopropyl (S)-2-((S)-2,4-bis(methylthio)buta namido)-6-diazo-5-oxohexanoate376549 isopropyl (S)-6-diazo-2-((S)-2-(ethylthio)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate445550 isopropyl (S)-2-((S)-2-(acetylthio)-4-(methylthio)butana mido)-6-diazo-5-oxohexanoate404551 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(methylthio)propan amido)-6-diazo-5-oxohexanoate431552 isopropyl (S)-6-diazo-2-(2-(isopropylthio)acet amido)-5-oxohexanoate330553 isopropyl (S)-6-diazo-2-((S)-2-(methylthio)-3-phenylpropanamido )-5-oxohexanoate392554 isopropyl (S)-6-diazo-2-((S)-2-(methylthio)-2-phenylacetamido)-5-oxohexanoate378555 isopropyl (S)-6-diazo-2-((S)-2-(methylthio)butana mido)-5-oxohexanoate330556 isopropyl (S)-6-diazo-2-((S)-3-methyl-2-(methylthio)butana mido)-5-oxohexanoate344557 cyclopentyl (S)-6-diazo-2-((S)-2-(methylthio)propan amido)-5-oxohexanoate342558 isopropyl (S)-6-diazo-5-oxo-2-((S)-thietane-2-carboxamido)hexan oate314559 methyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)pro panamido)-5-oxohexanoate304560 ethyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)pro panamido)-5-oxohexanoate318561 isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)pro panamido)-5-oxohexanoate332562 isopropyl (2S)-6-diazo-2-(2-(ethylsulfinyl)aceta mido)-5-oxohexanoate332563 S-isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)pro panamido)-5-oxohexanethioate348564 isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)-4-(methylthio)butana mido)-5-oxohexanoate392565 isopropyl (2S)-6-diazo-2-((2S)-2-(ethylsulfinyl)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate461566 isopropyl (2S)-2-((2S)-3-(1H-indol-3-yl)-2-(methylsulfinyl)pro panamido)-6-diazo-5-oxohexanoate447567 isopropyl (2S)-6-diazo-2-(2-(isopropylsulfinyl)a cetamido)-5-oxohexanoate346568 isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)-3-phenylpropanamido )-5-oxohexanoate408569 isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)-2-phenylacetamido)-5-oxohexanoate394570 isopropyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)but anamido)-5-oxohexanoate346571 isopropyl (2S)-6-diazo-2-((2S)-3-methyl-2-(methylsulfinyl)but anamido)-5-oxohexanoate360572 cyclopentyl (2S)-6-diazo-2-((2S)-2-(methylsulfinyl)pro panamido)-5-oxohexanoate358573 methyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)pr opanamido)-5-oxohexanoate320574 ethyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)pr opanamido)-5-oxohexanoate334575 isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)pr opanamido)-5-oxohexanoate348576 isopropyl (S)-6-diazo-2-(2-(ethylsulfonyl)aceta mido)-5-oxohexanoate348577 S-isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)pr opanamido)-5-oxohexanethioate364578 isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)-4-(methylthio)butana mido)-5-oxohexanoate408579 isopropyl (S)-6-diazo-2-((S)-2-(ethylsulfonyl)-3-(1H-indol-3-yl)propanamido)-5-oxohexanoate477580 isopropyl (S)-2-((S)-3-(1H-indol-3-yl)-2-(methylsulfonyl)pr opanamido)-6-diazo-5-oxohexanoate463581 isopropyl (S)-6-diazo-2-(2-(isopropylsulfonyl) acetamido)-5-oxohexanoate362582 isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)-3-phenylpropanamido )-5-oxohexanoate424583 isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)-2-phenylacetamido)-5-oxohexanoate410584 isopropyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)but anamido)-5-oxohexanoate362585 isopropyl (S)-6-diazo-2-((S)-3-methyl-2-(methylsulfonyl)but anamido)-5-oxohexanoate376586 cyclopentyl (S)-6-diazo-2-((S)-2-(methylsulfonyl)pr opanamido)-5-oxohexanoate374

[0146] It is noted that all compounds in compounds 1-586 that are not encompassed by the wording of the claims are considered as useful for understanding the invention. Only the compounds covered by the claims are part of the invention.Synthesis of Control Compounds:

[0147] Compound 60 of WO2017023774 (named "reference compound A") was obtained according to the synthesis route and operation steps of compound 60 in Page 124 of WO2017023774.

[0148] Compound 25 of WO2017023774 (named "reference compound 1") was obtained according to the synthesis route and operation steps of compound 25 in Page 100-101 of WO2017023774.

[0149] Compound 9 of WO2017023774 (named "reference compound 2") was obtained according to the synthesis route and operation steps of compound 9 in Page 87-88 of WO2017023774.

[0150] Compound 47 of WO2017023774 (named "reference compound 3") was obtained according to the synthesis route and operation steps of compound 47 in Page 115-116 of WO2017023774.Example 7 Plasma stability of different species

[0151] Reference compound A, reference compound 1, reference compound 2, compound 2, compound 3, compound 81, compound 443, compound 459 were provided for assay of plasma stability of compounds in different species, and they were shown as below:

[0152] For metabolic stability, plasma from dog, monkey, swine and human were used. For stability, prodrugs (1 µM) were spiked in respective solutions and incubated in an orbital shaker at 37 °C. 50 µL aliquots of the mixture in duplicate were removed, and the reaction quenched by addition of four times the volume of ice cold acetonitrile spiked with the internal standard (Dexamethasone 100 ng / mL). The samples were vortexed for 30 s and centrifuged at 15000g for 5 min. 100 µL of the supernatant was diluted with 100 µL of water and transferred to the 0.6 mL plastic tubes on 96-well plate. Prodrug disappearance was monitored over time using a liquid chromatography and tandem mass spectrometry (LC-MS / MS).

[0153] For LC-MS / MS, prodrugs were analyzed on a ExionLC AD HPLC system coupled to REF Triple Quad 5500+ mass spectrometer with an ESI interface on an Phenomenex Kinetex 5 µm C18 100A (2.1*50) mm UPLC column. The autosampler was temperature controlled and was operated at 4 °C. The mobile phase used for the chromatographic separation was composed of acetonitrile / water containing 0.1% formic acid and will run at a flow rate of 0.6 mL / min for 3.5 min using gradient elution. The column effluent was monitored using TSQ Vantage triple-quadrupole mass-spectrometric detector, equipped with an electrospray probe set in the positive ionization mode. Samples were introduced into the ionization source through a heated nebulized probe (400°C). Disappearance of prodrugs will be measured from ratio of peak areas of analyte to IS.

[0154] For quantification of compound remaining, disappearance of prodrugs was measured from ratio of peak areas of analyte to IS.

[0155] Figure 1 shows the plasma stability of compounds after incubation for 4 hours in the presence of dog, monkey, swine and human plasma. The data show that the Reference compound A, compound 2, compound 3, compound 81, compound 443, compound 459 was substantially intact in the presence of the dog, monkey, swine and human plasma for 4 hours, while few of reference compound 1 and reference compound 2 remained in such conditions.Example 8 Stability of liver microsomes of different species

[0156] Reference compound A, reference compound 1, reference compound 2, and compound 2, compound 3, compound 81, compound 443, compound 459 were provided for assay of stability of liver microsomes in different species.

[0157] For metabolic stability, microsomes from human, monkey, dog, rat and mouse were used. For stability, prodrugs (1 µM) were spiked in each microsomes matrix and incubated in an orbital shaker at 37 °C. Aliquots of 50 µL were taken from the reaction solution at 0, 15, 30, 45 and 60 min. The reaction was stopped by the addition of 4 volumes of cold acetonitrile with IS (100 nM alprazolam, 200 nM labetalol, 200 nM caffeine and 2 µM ketoprofen). Samples were centrifuged at 3, 220 g for 40 minutes. Aliquot of 100 µL of the supernatant was mixed with 100 µL of ultra-pure H 2 O and then used for LC-MS / MS analysis.

[0158] For LC-MS / MS, prodrugs were analyzed on an API 4000 instrument from AB Inc (Canada) with an ESI interface coupled to Shimadzu LC system on an Waters XSelect HSS T3 C18, 2.5µm, 2.1 x 30mm column. The mobile phase used for the chromatographic separation was composed of Phase A: water (0.1 % formic acid); Phase B: acetonitrile (0.1% formic acid) and will run at a flow rate of 1.0 mL / min for 1.0 min using gradient elution. Samples was introduced into the ionization source through a heated nebulized probe (500 °C). Disappearance of prodrugs will be measured from ratio of peak areas of analyte to IS.

[0159] For data analysis, peak areas were determined from extracted ion chromatograms. The slope value, k, was determined by linear regression of the natural logarithm of the remaining percentage of the parent drug vs. incubation time curve. The in vitro half-life (in vitro t 1 / 2 ) was determined from the slope value: in vitro t 1 / 2 = − 0.693 / k

[0160] Conversion of the in vitro t 1 / 2 (min) into the in vitro intrinsic clearance (in vitro CL int , in µL / min / mg protein) was done using the following equation (mean of duplicate determinations): in vitro CL int = 0.693 t 1 / 2 × volume of incubation μL amount of proteins mg

[0161] Table 1 shows the in vitro intrinsic clearance of compounds after incubation for 60 minutes in the presence of human, monkey, dog, rat and mouse liver microsomes. Table 1. In vitro Clint (µL / min / mg protein) of Test Compounds in Different Species of Liver MicrosomesCompounds HumanMonkeyDogRatMouseReference Compound 195.34167.2563.64123.55114.88Reference Compound 2110.42280.5650.25437.21125.68Reference Compound A118.61393.2060.4195.16152.92Compound 243.4431.7812.7062.4367.14Compound 3124.3346.3910.9049.4771.15Compound 8116.8225.975.49268.8360.81Compound 44373.52179.9281.89238.84407.55Compound 45918.88130.509.57114.9671.74 Example 9 Examination on the anti-tumor Efficacy in MC38 Syngeneics in C57BL / 6 mouse

[0162] Reference compound A, compound 2, compound 3, compound 81, compound 443, compound 459 were provided for the anti-tumor Efficacy in MC38 Syngeneics in C57BL / 6 mouse.

[0163] Animal species: Mus musculus; Strain: C57BL / 6; Age: 6-8 weeks; Sex: female. The MC38 tumor cells were maintained in vitro in DMEM medium supplemented with 10% FBS at 37 °C, 5% CO 2 . The cells growing in an exponential growth phase were harvested and counted for tumor inoculation. The culture MC38 were harvested, re-suspended in PBS containing 50% Matrigel at a density of 1×10 7< cells / mL. Each mouse was inoculated subcutaneously in the right flank region with 1×10 6< cells in 0.1 mL of PBS containing 50% Matrigel for tumor development.

[0164] The treatments were started when the mean tumor size reached 79-118mm 3< (average tumor size 96 mm 3< ). Each group contained 8 tumor bearing mice. Group 1 was treated with Vehicle (10%DMSO + 90% Saline), S.C., QD. Group 2 was given treatments with reference compound A at 2 µmol / kg, S.C., QD. Group 3 was given treatments with compound 2 at 2 µmol / kg, S.C., QD. The administration of test articles in each study group was shown in the following Table 2.

[0165] In vivo efficacy was examined according to absolute tumor growth inhibition (TGI) and the safety was evaluated according to weight change and survival in mice. Table 2Group Compound Dose (µmol / kg) Dosing Route Schedule 1Vehicle2S.C.QD×162Reference compound A2S.C.QD×263Compound 22S.C.QD×26 Body Weight

[0166] The results of the body weight changes in the tumor-bearing mice are shown in Table 3, Figure 2. Table 3. The body weight changes (%) of the mice in different groupsCompound Dose (µmol / kg) BW(g) (Mean ± SEM) BW Change (%) Beginning (D6) End (D21) Vehicle221.9±0.424.9±0.4+ 13.6Reference Compound A221.9±0.322.5±0.4+ 2.8Compound 2221.7±0.222.4±0.2+ 3.3 Tumor Volumes

[0167] The results of tumor sizes in different groups at different time points post tumor inoculation are shown in Table 4 and Figure 3. The tumor growth inhibition is summarized in Table 5. The result showed that the other treatment groups showed significant anti-tumor effect when compared to the vehicle group. Statistical analysis of difference in tumor volume among the groups was performed using one-way ANOVA followed by individual comparisons using Games-Howell post-hoc test (equal variance not assumed). All data was analyzed using SPSS 22.0 software. Table 4. Mean tumor volume in the different treatment groupsCompoun d Dose (µmo l / kg) TV (mm 3< ) (Mean ± SEM) D6 D10 D14 D18 D21 D25 D28 D31 Vehicle296± 4354±1 7909±4 21732±1 142778±1 88Reference compound A296± 4148±6196±2 5297±48399±74680±1 43928±1 531358±2 13Compound 2296± 4141±9140±1 0180±13263±32381±5 5496±6 2617±56 Table 5. Anti-tumor activity of test compounds in MC38 syngeneic model Compound Dose (µmol / kg) TV (mm 3< ) at D21 (Mean ± SEM) T / C (%) TGI (%) Pvalue (vs. Vehicle) Vehicle22778±188---Reference Compound A2399±7414.485.60.000Compound 22263±329.590.50.000 Example 10 Examination on the anti-tumor Efficacy in MC38 model in CES1c - / -mouse

[0168] Reference compound A and compound 2 obtained from example 2 were provided for the anti-tumor Efficacy in MC38 model in CES1c - / -mouse.

[0169] Animal species: Mus musculus; Strain: C57BL / 6-Ces1c em1Smoc< ; Age: 6-8 weeks; Sex: female. (Shanghai Model Organisms).The MC38 tumor cells were maintained in vitro in DMEM medium supplemented with 10% FBS at 37 °C, 5% CO 2 . The cells growing in an exponential growth phase were harvested and counted for tumor inoculation. The culture MC38 were harvested, re-suspended in PBS containing 50% Matrigel at a density of 1×10 7< cells / mL. Each mouse was inoculated subcutaneously in the right flank region with 1×10 6< in 0.1 mL of PBS containing 50% Matrigel for tumor development.

[0170] The treatments were started when the mean tumor size reached 52-132mm 3< (average tumor size 95 mm 3< ). Each group contained 5 tumor bearing mice. Group 1 was treated with Vehicle (10%DMSO + 90% Saline), S.C., QD(Subcutaneous injection, quaque die). Group 2 was given treatments with reference compound A at 2 µmol / kg, S.C., QD. Group 3 was given treatments with compound 2 at 2 µmol / kg, S.C., QD. The administration of test articles in each study group was shown in the following Table 6.

[0171] In vivo efficacy was examined according to absolute tumor growth inhibition (TGI) and the safety was evaluated according to weight change and survival in mice. Table 6Group Compound Dose (µmol / kg) Dosing Route Schedule 1Vehicle2S.C.QD×212Reference compound A2S.C.QD×213Compound 22S.C.QD×21 Body Weight

[0172] Group treated with reference compound A showed some body weight loss, but the group treated with vehicle and the group treated with compound 2 were well-tolerated by the tumor-bearing mice. The results of the body weight changes in the tumor-bearing mice are shown in Table 7, Figure 4. Table 7. The body weight changes (%) of the mice in different groupsCompound Dose (µmol / kg) BW(g) (Mean ± SEM) BW Change (%) Beginning (D6) End (D26) Vehicle218.0±0.320.3±0.3+ 12.8Reference Compound A219.2±0.217.6±0.9- 8.3Compound 2219.1±0.319.5±0.3+ 2.4 Tumor Volumes

[0173] The results of tumor sizes in different groups at different time points post tumor inoculation are shown in Table 8 and Figure 5. The tumor growth inhibition is summarized in Table 9. The result showed that all treatment groups showed significant anti-tumor effect when compared to the vehicle group. Statistical analysis of difference in tumor volume among the groups was performed using one-way ANOVA followed by individual comparisons using Games-Howell post-hoc test (equal variance not assumed). All data was analyzed using SPSS 22.0 software. Table 8. Mean tumor volume in the different treatment groupsCompoun d Dose (µmol / kg ) TV (mm 3< ) (Mean ± SEM) D6 D9 D12 D15 D20 D23 D26 Vehicle295±1 3259±1 3275±2 2448±2 9825±8 51300±24 22234±41 3Reference Compound A295±6275±3 3147±5195±2 3196±3 3183±33274±81Compound 2295±11193±2 0103±1 5131±2 1169±1 9219±21313±35 Table 9. Anti-tumor activity of test compounds in MC38 syngeneic model Compound Dose (µmol / kg) TV (mm 3< ) at D26 (Mean ± SEM) T / C (%) TGI (%) Pvalue (vs. Vehicle) Vehicle22234±413---Reference Compound A2274±8112.387.70.046Compound 22313±3514.086.00.052 Example 11 Examination on the anti-tumor Efficacy in MC38 model in C57BL / 6 mouse

[0174] Compound 2, compound 3, compound 81, compound 443 and compound 459 were provided for the anti-tumor Efficacy in MC38 model in C57BL / 6 mouse.

[0175] Animal species: Mus musculus; Strain: C57BL / 6; Age: 6-8 weeks; Sex: female. The MC38 tumor cells were maintained in vitro in DMEM medium supplemented with 10% FBS at 37 °C, 5% CO 2 . The cells growing in an exponential growth phase were harvested and counted for tumor inoculation. The culture MC38 were harvested, re-suspended in PBS containing 50% Matrigel at a density of 1×10 7< cells / mL. Each mouse was inoculated subcutaneously in the right flank region with 1×10 6< cells in 0.1 mL of PBS containing 50% Matrigel for tumor development.

[0176] The treatments were started when the mean tumor size reached 82-129mm 3< (average tumor size 102 mm 3< ). Each group contained 6 tumor bearing mice. Group 1 was treated with Vehicle (10%DMSO + 90% Saline), S.C., QD. Group 2 was given treatments with compound 2 at 2 µmol / kg, S.C., QD. Group 3 was given treatments with compound 81 at 2 µmol / kg, S.C., QD. Group 4 was given treatments with compound 443 at 2 µmol / kg, S.C., QD. Group 5 was given treatments with compound 459 at 2 µmol / kg, S.C., QD. Group 6 was given treatments with compound 3 at 2 µmol / kg, S.C., QD. The administration of test articles in each study group was shown in the following Table 10.

[0177] In vivo efficacy was examined according to absolute tumor growth inhibition (TGI) and the safety was evaluated according to weight change and survival in mice. Table 10Group Compound Dose (µmol / kg) Dosing Route Schedule 1Vehicle2S.C.QD×152Compound 22S.C.QD×153Compound 812S.C.QD×154Compound 4432S.C.QD×155Compound 4592S.C.QD×156Compound 32S.C.QD×15 Body Weight

[0178] The results of the body weight changes in the tumor-bearing mice are shown in Table 11, Figure 6. Table 11. The body weight changes (%) of the mice in different groupsCompound Dose (µmol / kg) BW(g) (Mean ± SEM) BW Change (%) Beginning (D6) End (D20) Vehicle219.9±0.523.6±0.8+18.6Compound 2219.8±0.221.1±0.3+6.4Compound 81219.8±0.320.2±0.5+1.9Compound 443219.9±0.622.3±0.5+11.9Compound 459219.9±0.321.1±0.5+6.3Compound 3219.9±0.521.5±0.4+7.8 Tumor Volumes

[0179] The results of tumor sizes in different groups at different time points post tumor inoculation are shown in Table 12 and Figure 7. The tumor growth inhibition is summarized in Table 13. The result showed that the other treatment groups showed significant anti-tumor effect when compared to the vehicle group. Statistical analysis of difference in tumor volume among the groups was performed using one-way ANOVA followed by individual comparisons using Games-Howell post-hoc test (equal variance not assumed). All data was analyzed using SPSS 22.0 software. Table 12. Mean tumor volume in the different treatment groupsCompound Dose (µmol / kg) TV (mm 3< ) (Mean ± SEM) D6 D10 D13 D17 D20 Vehicle2102±5451±37810±1141537±2162331±369Compound 22102±7167±17257±51306±43407±33Compound 812102±6141±9124±10176±13112±22Compound 4432102±6152±25267±65384±95500±119Compound 4592102±5148±22183±30281±65275±59Compound 32102±6145±16169±9215±27233±31 Table 13. Anti-tumor activity of test compounds in MC38 syngeneic model Compound Dose (µmol / kg) TV (mm 3< ) at D21 (Mean ± SEM) T / C (%) TGI (%) Pvalue (vs. Vehicle) Vehicle22331±369---Compound 22407±3317.582.50.022Compound 812112±224.895.20.012Compound 4432500±11921.578.50.023Compound 4592275±5911.888.20.016Compound 32233±3110.090.00.015

Claims

1. A compound or a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, and an isotopic substitution thereof, wherein the compound is selected from the group consisting of: 2isopropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate3methyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate4(S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoic acid6ethyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate9isopropyl (S)-6-diazo-2-(2-methoxyacetamido)-5-oxohexanoate10isopropyl (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate11isopropyl (S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate14isopropyl (S)-6-diazo-2-((S)-2-hydroxy-4-methylpentanamido)-5-oxohexanoate71isopropyl (S)-6-diazo-2-((S)-2-ethoxypropanamido)-5-oxohexanoate72isopropyl (S)-6-diazo-2-((S)-2-isopropoxypropanamido)-5-oxohexanoate74isopropyl (S)-6-diazo-2-(2-hydroxyacetamido)-5-oxohexanoate76isopropyl (S)-6-diazo-2-((S)-2-hydroxybutanamido)-5-oxohexanoate77isopropyl (S)-6-diazo-2-((S)-2-methoxybutanamido)-5-oxohexanoate78isopropyl (S)-6-diazo-2-((S)-2-ethoxybutanamido)-5-oxohexanoate79isopropyl (S)-6-diazo-2-((S)-2-isopropoxybutanamido)-5-oxohexanoate81isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate82isopropyl (S)-6-diazo-2-((S)-2-methoxy-3-methylbutanamido)-5-oxohexanoate83isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3-methylbutanamido)-5-oxohexanoate84isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3-methylbutanamido)-5-oxohexanoate86isopropyl (S)-6-diazo-2-((2S,3R)-2-hydroxy-3-methylpentanamido)-5-oxohexanoate87isopropyl (S)-6-diazo-2-((2S,3R)-2-methoxy-3-methylpentanamido)-5-oxohexanoate88isopropyl (S)-6-diazo-2-((2S,3R)-2-ethoxy-3-methylpentanamido)-5-oxohexanoate89isopropyl (S)-6-diazo-2-((2S,3R)-2-isopropoxy-3-methylpentanamido)-5-oxohexanoate91isopropyl (S)-6-diazo-2-((S)-2-hydroxypentanamido)-5-oxohexanoate92isopropyl (S)-6-diazo-2-((S)-2-methoxypentanamido)-5-oxohexanoate93isopropyl (S)-6-diazo-2-((S)-2-ethoxypentanamido)-5-oxohexanoate94isopropyl (S)-6-diazo-2-((S)-2-isopropoxypentanamido)-5-oxohexanoate96isopropyl (S)-6-diazo-2-((S)-2-methoxy-4-methylpentanamido)-5-oxohexanoate97isopropyl (S)-6-diazo-2-((S)-2-ethoxy-4-methylpentanamido)-5-oxohexanoate98isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-4-methylpentanamido)-5-oxohexanoate100isopropyl (S)-6-diazo-2-((S)-2-hydroxy-3,3-dimethylbutanamido)-5-oxohexanoate101isopropyl (S)-6-diazo-2-((S)-2-methoxy-3,3-dimethylbutanamido)-5-oxohexanoate102isopropyl (S)-6-diazo-2-((S)-2-ethoxy-3,3-dimethylbutanamido)-5-oxohexanoate103isopropyl (S)-6-diazo-2-((S)-2-isopropoxy-3,3-dimethylbutanamido)-5-oxohexanoate105isopropyl (S)-6-diazo-2-((S)-2-hydroxyhexanamido)-5-oxohexanoate106isopropyl (S)-6-diazo-2-((S)-2-methoxyhexanamido)-5-oxohexanoate107isopropyl (S)-6-diazo-2-((S)-2-ethoxyhexanamido)-5-oxohexanoate108isopropyl (S)-6-diazo-2-((S)-2-isopropoxyhexanamido)-5-oxohexanoate176isopropyl (S)-6-diazo-2-(3-methoxy-2-oxopropanamido)-5-oxohexanoate177isopropyl (S)-6-diazo-2-(3-hydroxy-2-oxopropanamido)-5-oxohexanoate183isopropyl (S)-6-diazo-2-(3-hydroxypropanamido)-5-oxohexanoate184isopropyl (S)-6-diazo-2-((S)-3-hydroxybutanamido)-5-oxohexanoate185isopropyl (S)-6-diazo-2-(3-methoxypropanamido)-5-oxohexanoate186isopropyl (S)-6-diazo-2-((S)-3-methoxybutanamido)-5-oxohexanoate187isopropyl (S)-6-diazo-2-((S)-3-hydroxy-2-methylpropanamido)-5-oxohexanoate188isopropyl (S)-6-diazo-2-((S)-3-methoxy-2-methylpropanamido)-5-oxohexanoate190isopropyl (S)-6-diazo-2-((2S,3R)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate191isopropyl (S)-6-diazo-2-((2S,3R)-3-methoxy-2-methylbutanamido)-5-oxohexanoate192isopropyl (S)-6-diazo-2-((2R,3R)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate193isopropyl (S)-6-diazo-2-((2R,3R)-3-methoxy-2-methylbutanamido)-5-oxohexanoate194isopropyl (S)-6-diazo-2-((2R,3S)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate195isopropyl (S)-6-diazo-2-((2R,3S)-3-methoxy-2-methylbutanamido)-5-oxohexanoate196isopropyl (S)-6-diazo-2-((R)-3-hydroxybutanamido)-5-oxohexanoate197isopropyl (S)-6-diazo-2-((2S,3S)-3-hydroxy-2-methylbutanamido)-5-oxohexanoate198isopropyl (S)-6-diazo-2-((2S,3S)-3-methoxy-2-methylbutanamido)-5-oxohexanoate203isopropyl (S)-6-diazo-2-((R)-3-methoxybutanamido)-5-oxohexanoate210isopropyl (S)-6-diazo-2-((R)-3-hydroxy-2-methylpropanamido)-5-oxohexanoate218isopropyl (S)-6-diazo-2-((R)-3-methoxy-2-methylpropanainido)-5-oxohexanoate323tert-butyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate330tert-butyl (S)-6-diazo-2-((R)-2-methoxypropanamido)-5-oxohexanoate443isopropyl (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate444isopropyl (S)-6-diazo-2-(2-hydroxy-2-methylpropanamido)-5-oxohexanoate445methyl (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate447methyl (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate448methyl (S)-6-diazo-2-(2-isopropoxyacetamido)-5-oxohexanoate449(S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoic acid452isopropyl (S)-6-diazo-2-(2-isopropoxyacetamido)-5-oxohexanoate458methyl (S)-6-diazo-2-(2-methoxyacetamido)-5-oxohexanoate459S-isopropyl (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate460(S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoic acid486isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate487(S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoic acid488methyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate489ethyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate490S-isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate491isopropyl (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoate492methyl-d3 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate493ethyl-2,2,2-d3 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate494isopropyl (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate495isopropyl (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate496ethyl-d5 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate497propan-2-yl-d7 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate498propan-2-yl-d7 (S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate499propan-2-yl-d7 (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate500propan-2-yl-d7 (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate501S-(propan-2-yl-d7) (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate502propan-2-yl-d7 (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate503methyl-d3 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate504ethyl-2,2,2-d3 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate505ethyl-d5 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate506propan-2-yl-d7 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate507propan-2-yl-d7 (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate508S-(propan-2-yl-d7) (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate509propan-2-yl-d7 (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoate510propan-2-yl-d7 (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate511methyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate-2-d512ethyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate-2-d513isopropyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate-2-d514isopropyl 6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate-2-d515S-isopropyl 6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate-2-d516isopropyl 6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate-2-d517isopropyl 6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate-2-d518isopropyl 6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate-2-d519propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate520propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate521S-(propan-2-yl-1,1,1,3,3,3-d6) (S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate522propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoate523propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate524propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate525propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate526propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanoate527propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-(ethoxy-2,2,2-d3)acetamido)-5-oxohexanoate528S-(propan-2-yl-1,1,1-d3) (2S)-6-diazo-2-((S)-2-(methoxy-d3)propanamido)-5-oxohexanethioate529propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-(methoxy-d3)-4-(methylthio)butanamido)-5-oxohexanoat e530propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-(ethoxy-d5)acetamido)-5-oxohexanoate531propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-hydroxypropanamido)-5-oxohexanoate532propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-hydroxy-3-methylbutanamido)-5-oxohexanoate533propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate534propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate535S-(propan-2-yl-1,1,1,3,3,3-d6) (S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate536propan-2-yl-1,1,1,3,3,3-d6 (S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate537propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanoate538propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-(2-ethoxyacetamido)-5-oxohexanoate539S-(propan-2-yl-1,1,1-d3) (2S)-6-diazo-2-((S)-2-methoxypropanamido)-5-oxohexanethioate540propan-2-yl-1,1,1-d3 (2S)-6-diazo-2-((S)-2-methoxy-4-(methylthio)butanamido)-5-oxohexanoate.

2. A compound or a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, and an isotopic substitution thereof according to claim 1, wherein the compound is selected from the group consisting of:

3. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-2, wherein the compound is 4. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof according to any one of claims 1-3; and a pharmaceutically acceptable carrier, diluent or excipient.

5. The compound or the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof according to any one of claims 1-3; or the pharmaceutical composition of claim 4 for use as a medicament.

6. The compound or the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof according to any one of claims 1-3; or the pharmaceutical composition of claim 4 for use in the treatment of a cancer.

7. The compound or the pharmaceutically acceptable salt thereof, the stereoisomer thereof, the tautomer thereof, and the isotopic substitution thereof or the pharmaceutical composition for use of claim 6, wherein the cancer is selected from lung cancer, pancreatic cancer, liver cancer, breast cancer, colon cancer, leukemia, glioblastoma or head and neck cancer.