Wee1 inhibitors and their applications

Abstract

The present invention provides a series of novel compounds having Wee1 inhibitory activity represented by formula 1, and their use in the manufacture of medicines. TIFF2024520969000171.tif46170

Description

[Technical Field]

[0001] This invention relates to novel compounds having Wee1 inhibitory activity and their use in the manufacture of pharmaceuticals. [Background technology]

[0002] The cell cycle is a highly regulated and controlled process designed to respond to specific stimuli and ensure that cells proliferate only under appropriate conditions. A normal cell cycle consists of the G1 phase, S phase (DNA synthesis), G2 phase, and M phase (cell division). Several cycle-blocking checkpoints exist in phases such as G1-S, S, and G2-M, which are used to maintain genomic integrity and provide time to repair damaged DNA before mitosis. The Wee1 protein is a tyrosine kinase that is a major component of the G2-M cell cycle checkpoint, preventing cellular DNA damage from leading to mitosis. CDK1 (Cyclin-dependent kinase 1) is kept inactive by phosphorylation of Wee1 at tyrosine 15, and then CDK1 is phosphorylated at threonine 14 by myelin transcription factor (MYT1). Therefore, Wee1 is a negative regulator of mitosis in the G2-M transition, playing a crucial role as a watchdog. Wee1 is overexpressed in many malignancies, including liver cancer, breast cancer, malignant gliomas, melanomas, and adult and pediatric brain tumors. Some of these tumor cells have abnormalities in the G1 checkpoint, and inhibition of Wee1 activity leads to a malfunction of the G2 phase checkpoint, ultimately resulting in cell division and death with unrepaired damaged DNA. Therefore, Wee1 inhibitors play a vital role in anticancer drug therapy and are currently a hot topic in anticancer drug development.

[0003] Although low molecular weight Wee1 inhibitors have been reported (such as Patent Document 1 and Patent Document 2), no Wee1 inhibitor has been approved yet. The compound with the fastest development progress is AZD-1775, which has entered Phase II clinical trials. However, the incidence of side effects in clinical trials is high, and the development of new Wee1 inhibitors with better activity and high safety is required.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

[0005] The present invention provides a compound represented by Formula 1, its deuterium compound, its stereoisomer, or its pharmaceutically acceptable salt. TIFF0007866564000001.tif46170[wherein R 1 is hydrogen, halogen, cyano group, -C 1~6 alkyl group, -C 2~6 alkenyl group, -C 2~6 alkynyl group, halogen-substituted -C 1~6 alkyl group, halogen-substituted -C 2~6 alkenyl group, halogen-substituted -C 2~6 alkynyl group, -C 0~4 alkylene group -OR 11 、-C 0~4 alkylene group -NR 12 R 12 selected from the group consisting of, R 11 is -C 1~6 alkyl group, -C 2~6 alkenyl group, -C 2~6 alkynyl group, halogen-substituted -C 1~6 alkyl group, halogen-substituted -C 2~6 alkenyl group, halogen-substituted -C 2~6Selected from the group consisting of alkynyl groups, Each R 12 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, The C ring is, 10 Selected from the group consisting of, TIFF0007866564000002.tif36170 R 2 However, selected from the group consisting of equation 11, TIFF0007866564000003.tif24170 R 21 、R 22 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl alkyl group, -OR 24 Selected from the group consisting of, Each R 24 However, each is independent of hydrogen and -C. 1~6 Selected from the group consisting of alkyl groups, R 23 、R 3 However, together with the atoms that link to them, they form a 4-membered carbocykyl group, a 5-membered carbocykyl group, a 6-membered carbocykyl group, a 7-membered carbocykyl group, a 5-membered heterocycloalkyl group, and a 6-membered heterocycloalkyl group. R 5 However, hydrogen, -C 1~6 Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of equation 5, TIFF0007866564000004.tif113170TIFF0007866564000005.tif9166 represent single or double bonds, Y 1 , Y 2 , Y 3 , Y 4 However, N and CR are independent of each other. Y Selected from the group consisting of, Each RY However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, The B ring is selected from the group consisting of a 3-12 membered carbocyclyl group and a 4-12 membered heterocycloalkyl group, and the carbocyclyl group and heterocycloalkyl group further consist of one, two, three, four, or five R B It may be replaced with, Each R B However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR B1 , -C 0~4 Alkylene group -OC(O)R B1 , -C 0~4 Alkylene group-SR B1 , -C 0~4 Alkylene group -S(O)2R B1 , -C 0~4 Alkylene group -S(O)R B1 , -C 0~4 Alkylene group -S(O)2NR B1 R B1 , -C0~4 alkylene-S(O)NR B1 R B1 、-C 0~4 alkylene-C(O)R B1 、-C 0~4 alkylene-C(O)OR B1 、-C 0~4 alkylene-C(O)NR B1 R B1 、-C 0~4 alkylene-NR B1 R B1 、-C 0~4 alkylene-NR B1 C(O)R B1 、selected from the group consisting of a 3- to 12-membered carbocyclic group and a 4- to 12-membered heterocycloalkyl group, wherein the carbocyclic group and the heterocycloalkyl group may be further substituted with one, two, three, four or five R B1 s, or two independent R B s together with the atoms to which they are attached form a group of formula 6, TIFF0007866564000006.tif31170each R B1 is independently selected from the group consisting of hydrogen, -C 1~6 alkyl, -C 2~6 alkenyl, -C<9999999>alkynyl, halogen-substituted -C 1~6 alkyl, halogen-substituted -C 2~6 alkenyl, halogen-substituted -C 2~6 alkynyl, R 6 、R 7 、R 8 、R 9 is independently selected from the group consisting of hydrogen, halogen, cyano group, -C 1~6 alkyl, -C 2~6 alkenyl, -C 2~6 alkynyl, halogen-substituted -C 1~6 alkyl, halogen-substituted -C 2~6 alkenyl, halogen-substituted -C 2~6 alkynyl, -C 0~4 alkylene-OH, -C 0~4 alkylene-O(C 1~6 It should be noted that there seems to be an error in the original text where the "9999999" is likely an incorrect placeholder. If this is a specific chemical structure code, it needs to be corrected for a more accurate translation. Also, the overall text relates to chemical functional groups and substitution patterns which are quite complex and might require some chemical knowledge for a full understanding of its implications.(alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Alternatively, R 6 , R 7 However, together with the atoms linked to them, they form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or R 8 , R 9 However, together with the atoms that link to them, they form a 3-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. Y 5 , Y 6 However, each is independent of the chemical bond, -C 0~4 Alkylene groups -O-, -C 0~4 Alkylene groups -S-, -C 0~4 Alkylene group-NR Y51 -, CR Y51 R Y51 Selected from the group consisting of, Each R Y51 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Y 7 However, O, S, NR Y71 Selected from the group consisting of, R Y71 However, hydrogen, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 10 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups.

[0006] Furthermore, the C ring is selected from the group consisting of formula 12. TIFF0007866564000007.tif38170 Among these, m is selected from the group consisting of 0, 1, 2, and 3.

[0008] The present invention provides compounds represented by formula 1, deuterium compounds thereof, stereoisomers thereof, or pharmaceutically acceptable salts thereof. TIFF0007866564000008.tif46170 [Among them, R 1 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 11 、-C 0~4 Alkylene group-NR 12 R 12 Selected from the group consisting of, R 11 However, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Each R 12 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, The C ring is selected from the group consisting of Equation 7. 、 TIFF0007866564000009.tif114170 R 2 However, selected from the group consisting of equation 13, TIFF0007866564000010.tif25170 R 21 、R 22 However, each is independent of hydrogen and -C. 1~6 Selected from the group consisting of alkyl groups, R 5 However, hydrogen, -C 1~6 Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of equation 5, TIFF0007866564000011.tif113170TIFF0007866564000012.tif9166 However, it represents a single bond or a double bond. Y 1 、Y 2 、Y 3 、Y 4 However, N and CR are independent of each other. Y Selected from the group consisting of, Each R Y However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (Alkyl alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, The B ring is selected from the group consisting of a 3-12 membered carbocyclyl group and a 4-12 membered heterocycloalkyl group, and the carbocyclyl group and heterocycloalkyl group further consist of one, two, three, four, or five R B It may be replaced with, Each R B However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR B1 、-C 0~4 Alkylene group -OC(O)R B1 、-C 0~4 Alkylene group-SR B1 、-C 0~4 Alkylene group -S(O) 2 R B1 、-C 0~4 Alkylene group -S(O)R B1 、-C 0~4 Alkylene group -S(O) 2 NR B1 R B1 、-C 0~4 Alkylene group -S(O)NR B1 R B1 、-C 0~4 Alkylene group -C(O)R B1 、-C 0~4 Alkylene group -C(O)OR B1 、-C 0~4 Alkylene group -C(O)NR B1 R B1 、-C 0~4 Alkylene group-NR B1 R B1 、-C 0~4 Alkylene group-NR B1 C(O)R B1 A selected group consisting of a 3-12 membered carbocyclyl group and a 4-12 membered heterocycloalkyl group, wherein the carbocyclyl group and heterocycloalkyl group are further divided into one, two, three, four, or five R groups. B1 It may be replaced by, or by two independent R B However, together with the atoms that connect to them, they form the group of formula 6, TIFF0007866564000013.tif31170 Each RB1 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, R 6 、R 7 、R 8 、R 9 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Alternatively, R 6 、R 7 However, together with the atoms linked to them, they form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or R 8 、R 9 However, together with the atoms that link to them, they form a 3-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. Y 5 、Y 6 However, each is independent of the chemical bond, -C 0~4 Alkylene groups -O-, -C 0~4 Alkylene groups -S-, -C 0~4 Alkylene group-NRY51 -, CR Y51 R Y51 Selected from the group consisting of, Each R Y51 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Y 7 However, O, S, NR Y71 Selected from the group consisting of, R Y71 However, hydrogen, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 10 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups.

[0017] The present invention provides compounds represented by formula 1, deuterium compounds thereof, stereoisomers thereof, or pharmaceutically acceptable salts thereof. TIFF0007866564000014.tif46170 [Among them, R 1 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 11 、-C 0~4 Alkylene group-NR 12 R 12 Selected from the group consisting of, R 11 However, -C1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Each R 12 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, The C ring is selected from the group consisting of equation 2. TIFF0007866564000015.tif63170 X 1 、X 2 、X 4 However, N and CR are independent of each other. 4 Selected from the group consisting of, X 3 However, N, CR 3 Selected from the group consisting of, X 5 However, O, S, NR 4 Selected from the group consisting of, X 6 However, CR 4 Selected from the group consisting of N, X 8 However, CR 4 R 4 Selected from the group consisting of O, X 7 However, S, NR 4 Selected from the group consisting of, X9 However, CR 4 R 4 Selected from the group consisting of, R 2 However, selected from the group consisting of equation 3, TIFF0007866564000016.tif31170 R 21 、R 22 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 24 、-C 0~4 Alkylene group-NR 24 R 24 Selected from the group consisting of, Each R 24 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 21 、R 22 However, together with the atoms linked to them, they form a 3-8 membered carbocyl group, a 4-8 membered heterocycloalkyl group, and a group of formula 4. TIFF0007866564000017.tif31170 R 23 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -C(O)R 25 、-C 0~4 Alkylene group -C(O)NR 25 R 25 、-C 0~4 Alkylene group -C(O)OR 25 、-C 0~4 Alkylene group -S(O) 2 R 25 、-C 0~4 Alkylene group -S(O)R 25 、-C 0~4 Alkylene group -S(O)(NH)R 25 、-C 0~4 Alkylene group -S(O) 2 NR 25 R 25 、-C 0~4 Alkylene group -S(O)NR 25 R 25 、-C 0~4 Alkylene group -S(O)(NH)NR 25 R 25 、-C 0~4 Alkylene group-OR 25 、-C 0~4 Alkylene group -OC(O)R 25 、-C 0~4 Alkylene group -OS(O) 2 R 25 、-C 0~4 Alkylene group -OS(O)R 25 、-C 0~4 Alkylene group-NR 25 R 25 、-C 0~4 Alkylene group-NR 25 C(O)R25 、-C 0~4 Alkylene group-NR 25 S(O) 2 R 25 、-C 0~4 Alkylene group-NR 25 S(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O)(NH)R 25 Selected from the group consisting of, Each R 25 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 23 、R 3 However, together with the atoms linked to them, they form a 4-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. R 3 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, hydroxy-substituted -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Each R 4 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 5 However, hydrogen, -C 1~6 Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of Equation 18, TIFF0007866564000018.tif37170Y 1 , Y 2 , Y 3 , Y 4 However, N and CR are independent of each other. Y Selected from the group consisting of, Each R Y However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl alkyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 6 , R 7 , R 8 , R 9 However, each is independent of hydrogen and -C. 1~6 Selected from the group consisting of alkyl groups, Alternatively, R 6 , R 7 However, together with the atoms linked to them, they form a 3-membered carbocyacrylic group, a 4-membered carbocyacrylic group, a 5-membered carbocyacrylic group, a 6-membered carbocyacrylic group, a 4-membered heterocycloalkyl group, a 5-membered heterocycloalkyl group, or a 6-membered heterocycloalkyl group, or R 8 , R 9 However, together with the atoms that link to them, they form a 3-membered carbocyacrylic group, a 4-membered carbocyacrylic group, a 5-membered carbocyacrylic group, a 6-membered carbocyacrylic group, a 4-membered heterocycloalkyl group, a 5-membered heterocycloalkyl group, and a 6-membered heterocycloalkyl group. R B However, hydrogen, -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl alkyl group, -S(O)2R B1 ,-S(O)R B1 , -C(O)R B1 , -C(O)OR B1 Selected from the group consisting of, Each R B1 However, each is independent of hydrogen and -C. 1~6 Alkyl, halogen-substituted -C 1~6 Selected from the group consisting of alkyl groups 、 R 10 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups.

[0018] Furthermore, ring A is selected from the group consisting of equation 19. TIFF0007866564000019.tif49170

[0019] The present invention provides compounds represented by formula 1, deuterium compounds thereof, stereoisomers thereof, or pharmaceutically acceptable salts thereof. TIFF0007866564000020.tif46170 [Among them, R 1 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 11 、-C 0~4 Alkylene group-NR 12 R 12 Selected from the group consisting of, R 11 However, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Each R12 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, The C ring is selected from the group consisting of equation 2. TIFF0007866564000021.tif63170 X 1 、X 2 、X 4 However, N and CR are independent of each other. 4 Selected from the group consisting of, X 3 However, N, CR 3 Selected from the group consisting of, X 5 However, O, S, NR 4 Selected from the group consisting of, X 6 However, CR 4 Selected from the group consisting of N, X 8 However, CR 4 R 4 Selected from the group consisting of O, X 7 However, S, NR 4 Selected from the group consisting of, X 9 However, CR 4 R 4 Selected from the group consisting of, R 2 However, selected from the group consisting of equation 3, TIFF0007866564000022.tif31170 R21 、R 22 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 24 、-C 0~4 Alkylene group-NR 24 R 24 Selected from the group consisting of, Each R 24 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 21 、R 22 However, together with the atoms linked to them, they form a 3-8 membered carbocyl group, a 4-8 membered heterocycloalkyl group, and a group of formula 4. TIFF0007866564000023.tif31170 R 23 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -C(O)R 25 、-C 0~4 Alkylene group -C(O)NR 25 R 25 、-C 0~4 Alkylene group -C(O)OR 25 、-C 0~4 Alkylene group -S(O) 2 R 25 、-C 0~4 Alkylene group -S(O)R 25 、-C 0~4 Alkylene group -S(O)(NH)R 25 、-C 0~4 Alkylene group -S(O) 2 NR 25 R 25 、-C 0~4 Alkylene group -S(O)NR 25 R 25 、-C 0~4 Alkylene group -S(O)(NH)NR 25 R 25 、-C 0~4 Alkylene group-OR 25 、-C 0~4 Alkylene group -OC(O)R 25 、-C 0~4 Alkylene group -OS(O) 2 R 25 、-C 0~4 Alkylene group -OS(O)R 25 、-C 0~4 Alkylene group-NR 25 R 25 、-C 0~4 Alkylene group-NR 25 C(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O) 2 R 25 、-C 0~4 Alkylene group-NR 25 S(O)R 25、-C 0~4 Alkylene group-NR 25 S(O)(NH)R 25 Selected from the group consisting of, Each R 25 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 23 、R 3 However, together with the atoms linked to them, they form a 4-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. R 3 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, hydroxy-substituted -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Each R 4 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 5 However, hydrogen, -C 1~6 Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of equation 20, TIFF0007866564000024.tif35170Y 1 , Y 2 , Y 4 However, N and CR are independent of each other. Y Selected from the group consisting of, Each R Y However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl alkyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R B However, hydrogen, -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl alkyl group, -S(O)2R B1 ,-S(O)R B1 , -C(O)RB1 , -C(O)OR B1 Selected from the group consisting of, Each R B1 However, each is independent of hydrogen and -C. 1~6 Alkyl, halogen-substituted -C 1~6 Selected from the group consisting of alkyl groups, Y 5 However, chemical bonds, O, S, NR Y51 CR Y51 R Y51 Selected from the group consisting of, Each R Y51 However, each is independent of hydrogen and -C. 1~6 Selected from the group consisting of alkyl groups 、 R 10 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups.

[0020] Furthermore, ring A is selected from the group consisting of equation 21. TIFF0007866564000025.tif32170

[0021] The present invention provides compounds represented by formula 1, deuterium compounds thereof, stereoisomers thereof, or pharmaceutically acceptable salts thereof. TIFF0007866564000026.tif46170 [Among them, R 1 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 11 、-C 0~4 Alkylene group-NR 12 R 12 Selected from the group consisting of, R 11 However, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Each R 12 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, The C ring is selected from the group consisting of equation 2. TIFF0007866564000027.tif63170 X 1 、X 2 、X 4 However, N and CR are independent of each other. 4 Selected from the group consisting of, X 3 However, N, CR 3 Selected from the group consisting of, X 5 However, O, S, NR 4 Selected from the group consisting of, X 6 However, CR 4 Selected from the group consisting of N, X 8 However, CR 4 R 4 Selected from the group consisting of O, X 7 However, S, NR 4 Selected from the group consisting of, X 9 However, CR 4 R 4 Selected from the group consisting of, R 2 However, selected from the group consisting of equation 3, TIFF0007866564000028.tif31170 R 21 、R 22 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 24 、-C 0~4 Alkylene group-NR 24 R 24 Selected from the group consisting of, Each R 24 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 21 、R 22 However, together with the atoms linked to them, they form a 3-8 membered carbocyl group, a 4-8 membered heterocycloalkyl group, and a group of formula 4. TIFF0007866564000029.tif31170 R 23 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -C(O)R 25 、-C 0~4 Alkylene group -C(O)NR 25 R 25 、-C 0~4 Alkylene group -C(O)OR 25 、-C 0~4 Alkylene group -S(O) 2 R 25 、-C 0~4 Alkylene group -S(O)R 25 、-C 0~4 Alkylene group -S(O)(NH)R 25 、-C 0~4 Alkylene group -S(O) 2 NR 25 R 25 、-C 0~4 Alkylene group -S(O)NR 25 R 25 、-C 0~4 Alkylene group -S(O)(NH)NR 25 R25 、-C 0~4 Alkylene group-OR 25 、-C 0~4 Alkylene group -OC(O)R 25 、-C 0~4 Alkylene group -OS(O) 2 R 25 、-C 0~4 Alkylene group -OS(O)R 25 、-C 0~4 Alkylene group-NR 25 R 25 、-C 0~4 Alkylene group-NR 25 C(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O) 2 R 25 、-C 0~4 Alkylene group-NR 25 S(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O)(NH)R 25 Selected from the group consisting of, Each R 25 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 23 、R 3 However, together with the atoms linked to them, they form a 4-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. R 3 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, hydroxy-substituted -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Each R 4 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 5 However, hydrogen, -C 1~6 Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of equation 22, TIFF0007866564000030.tif45170TIFF0007866564000031.tif9166 represents a single bond or a double bond, Y 1 、Y 2 、Y 4 are each independently selected from the group consisting of N, CR Y and, each R Y is independently selected from the group consisting of hydrogen, halogen, cyano group, -C 1~6 alkyl group, halogen-substituted -C 1~6 alkyl group, -C 0~4 alkylene group -OH, -C 0~4 alkylene group -O(C 1~6 alkyl group), -C 0~4 alkylene group -NH2, -C 0~4 alkylene group -NH(C 1~6 alkyl group), -C 0~4 alkylene group -N(C 1~6 alkyl group)(C 1~6 alkyl group) and is selected from the group consisting of, R B is hydrogen, -C 1~6 alkyl group, halogen-substituted -C 1~6 alkyl group, -S(O)2R B1 、-S(O)R B1 、-C(O)R B1 、-C(O)OR B1 and is selected from the group consisting of, each R B1 is independently selected from the group consisting of hydrogen, -C 1~6 alkyl group, halogen-substituted -C 1~6 alkyl group and is selected from the group consisting of, Y 5 、Y 6 are each independently selected from the group consisting of a chemical bond, -C 0~1 alkylene group -O-, -C 0~1 alkylene group -S-, -C 0~1 alkylene group -NR Y51 -, CR Y51 R Y51 and is selected from the group consisting of, each R Y51 is independently selected from the group consisting of hydrogen, -C1~6 Selected from the group consisting of alkyl groups 、 R 10 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups.

[0022] Furthermore, ring A is selected from the group consisting of equation 23. TIFF0007866564000032.tif96170

[0023] The present invention provides compounds represented by formula 1, deuterium compounds thereof, stereoisomers thereof, or pharmaceutically acceptable salts thereof. TIFF0007866564000033.tif46170 [Among them, R 1 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 11 、-C 0~4 Alkylene group-NR 12R 12 Selected from the group consisting of, R 11 However, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Each R 12 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, The C ring is selected from the group consisting of equation 2. TIFF0007866564000034.tif63170 X 1 、X 2 、X 4 However, N and CR are independent of each other. 4 Selected from the group consisting of, X 3 However, N, CR 3 Selected from the group consisting of, X 5 However, O, S, NR 4 Selected from the group consisting of, X 6 However, CR 4 Selected from the group consisting of N, X 8 However, CR 4 R 4 Selected from the group consisting of O, X7 However, S, NR 4 Selected from the group consisting of, X 9 However, CR 4 R 4 Selected from the group consisting of, R 2 However, selected from the group consisting of equation 3, TIFF0007866564000035.tif31170 R 21 、R 22 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 24 、-C 0~4 Alkylene group-NR 24 R 24 Selected from the group consisting of, Each R 24 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 21 、R 22 However, together with the atoms linked to them, they form a 3-8 membered carbocyl group, a 4-8 membered heterocycloalkyl group, and a group of formula 4. TIFF0007866564000036.tif31170 R 23 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -C(O)R 25 、-C 0~4 Alkylene group -C(O)NR 25 R 25 、-C 0~4 Alkylene group -C(O)OR 25 、-C 0~4 Alkylene group -S(O) 2 R 25 、-C 0~4 Alkylene group -S(O)R 25 、-C 0~4 Alkylene group -S(O)(NH)R 25 、-C 0~4 Alkylene group -S(O) 2 NR 25 R 25 、-C 0~4 Alkylene group -S(O)NR 25 R 25 、-C 0~4 Alkylene group -S(O)(NH)NR 25 R 25 、-C 0~4 Alkylene group-OR 25 、-C 0~4 Alkylene group -OC(O)R 25 、-C 0~4 Alkylene group -OS(O) 2 R 25 、-C 0~4 Alkylene group -OS(O)R 25 、-C 0~4 Alkylene group-NR 25 R25 、-C 0~4 Alkylene group-NR 25 C(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O) 2 R 25 、-C 0~4 Alkylene group-NR 25 S(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O)(NH)R 25 Selected from the group consisting of, Each R 25 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 23 、R 3 However, together with the atoms linked to them, they form a 4-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. R 3 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, hydroxy-substituted -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Each R 4 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 5 However, hydrogen, -C 1~6 Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of Equation 24, TIFF0007866564000037.tif40170Y 1 However, N, CR Y Selected from the group consisting of, R Y However, hydrogen, halogen, cyano group, -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl alkyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group -NH2, -C 0~4 Alkylene group -NH(C) 1~6(alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Ring B is selected from the group consisting of a 3-8 membered monocyclic carbocyclyl group and a 4-8 membered monocyclic heterocycloalkyl group, and the monocyclic carbocyclyl group and monocyclic heterocycloalkyl group further have one, two, three, four or five R B It may be replaced with, Each R B However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl, halogen-substituted -C 1~6 alkyl group, -OR B1 , -SR B1 -S(O)2R B1 ,-S(O)R B1 , -C(O)R B1 , -C(O)OR B1 , -NR B1 R B1 A group consisting of, or two independent R B However, together with the atoms that are linked to them, they form the group of formula 25, TIFF0007866564000038.tif27170 Each R B1 However, each is independent of hydrogen and -C. 1~6 Alkyl, halogen-substituted -C 1~6 Selected from the group consisting of alkyl groups, Y 7 However, O, S, NR Y71 Selected from the group consisting of, R Y71 However, hydrogen, -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl alkyl group, -C 1~4 Alkylene group -OH, -C 1~4 Alkylene group -O(C) 1~6 (alkyl group), -C 1~4 Alkylene group -NH2, -C 1~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 1~4 Alkylene group -N(C) 1~6 (Alkyl group)(C1~6 Selected from the group consisting of alkyl groups 、 R 10 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups.

[0024] Furthermore, ring A is selected from the group consisting of equation 26. TIFF0007866564000039.tif84170

[0026] The present invention provides compounds represented by formula 1, deuterium compounds thereof, stereoisomers thereof, or pharmaceutically acceptable salts thereof. TIFF0007866564000040.tif46170 [Here, R 1 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 11 、-C 0~4 Alkylene group-NR 12R 12 Selected from the group consisting of, R 11 However, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Each R 12 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, The C ring is selected from the group consisting of equation 2. TIFF0007866564000041.tif63170 X 1 、X 2 、X 4 However, N and CR are independent of each other. 4 Selected from the group consisting of, X 3 However, N, CR 3 Selected from the group consisting of, X 5 However, O, S, NR 4 Selected from the group consisting of, X 6 However, CR 4 Selected from the group consisting of N, X 8 However, CR 4 R 4 Selected from the group consisting of O, X7 However, S, NR 4 Selected from the group consisting of, X 9 However, CR 4 R 4 Selected from the group consisting of, R 2 However, selected from the group consisting of equation 3, TIFF0007866564000042.tif31170 R 21 、R 22 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group-OR 24 、-C 0~4 Alkylene group-NR 24 R 24 Selected from the group consisting of, Each R 24 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 21 、R 22 However, together with the atoms linked to them, they form a 3-8 membered carbocyl group, a 4-8 membered heterocycloalkyl group, and a group of formula 4. TIFF0007866564000043.tif31170 R 23 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -C(O)R 25 、-C 0~4 Alkylene group -C(O)NR 25 R 25 、-C 0~4 Alkylene group -C(O)OR 25 、-C 0~4 Alkylene group -S(O) 2 R 25 、-C 0~4 Alkylene group -S(O)R 25 、-C 0~4 Alkylene group -S(O)(NH)R 25 、-C 0~4 Alkylene group -S(O) 2 NR 25 R 25 、-C 0~4 Alkylene group -S(O)NR 25 R 25 、-C 0~4 Alkylene group -S(O)(NH)NR 25 R 25 、-C 0~4 Alkylene group-OR 25 、-C 0~4 Alkylene group -OC(O)R 25 、-C 0~4 Alkylene group -OS(O) 2 R 25 、-C 0~4 Alkylene group -OS(O)R 25 、-C 0~4 Alkylene group-NR 25 R25 、-C 0~4 Alkylene group-NR 25 C(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O) 2 R 25 、-C 0~4 Alkylene group-NR 25 S(O)R 25 、-C 0~4 Alkylene group-NR 25 S(O)(NH)R 25 Selected from the group consisting of, Each R 25 However, each is independent of hydrogen and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Selected from the group consisting of alkynyl groups, Alternatively, R 23 、R 3 However, together with the atoms linked to them, they form a 4-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. R 3 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, hydroxy-substituted -C 1~6 Alkyl, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, Each R 4 However, each is independent of hydrogen, halogen, cyano group, and -C. 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups, R 5 However, hydrogen, -C 1~6 Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of Equation 28 、 TIFF0007866564000044.tif121170 R 10 However, hydrogen, halogen, cyano group, -C 1~6 Alkyl alkyl group, -C 2~6 Alkenyl group, -C 2~6 Alkynyl group, halogen-substituted -C 1~6 Alkyl, halogen-substituted -C 2~6 Alkenyl group, halogen-substituted -C 2~6 Alkynyl group, -C 0~4 Alkylene group -OH, -C 0~4 Alkylene group -O(C) 1~6 (alkyl group), -C 0~4 Alkylene group - NH 2 、-C 0~4 Alkylene group -NH(C) 1~6 (alkyl group), -C 0~4 Alkylene group -N(C) 1~6 (Alkyl group)(C 1~6 Selected from the group consisting of alkyl groups.

[0027] The present invention Compounds selected from the group consisting of formula 29 The present invention provides the deuterium compound, its stereoisomer, or a pharmacoposifiable salt thereof. TIFF0007866564000045.tif246170TIFF0007866564000046.tif238170TIFF0007866564000047.tif231170 TIFF0007866564000048.tif247170TIFF0007866564000049.tif238170TIFF0007866564000050.tif253170 TIFF0007866564000051.tif229169TIFF0007866564000052.tif220169TIFF0007866564000053.tif234169 TIFF0007866564000054.tif244169TIFF0007866564000055.tif250169TIFF0007866564000056.tif140169

[0028] The present invention further provides the use of any of the compounds described above, their deuterium compounds, their stereoisomers, or pharmaceutically acceptable salts thereof in the production of Wee1 inhibitors. The present invention further provides the use of any of the compounds described above, their deuterium compounds, their stereoisomers, or pharmaceutically acceptable salts thereof in the manufacture of pharmaceuticals for the prevention and / or treatment of cancer. The present invention further provides a pharmaceutical composition comprising a formulation comprising any of the compounds described above, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The above pharmaceutical compositions further include pharmacologically acceptable carriers, additives, and mediators.

[0029] The compounds and derivatives provided in this invention may be named according to the nomenclature of IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, Columbus, OH). Definitions of terms used in this invention: Unless otherwise specified, the first definition provided herein for a base or term applies throughout this specification. Terms not specifically defined herein should be given the meaning that a person skilled in the art can give in light of the disclosure and context.

[0030] "Substitution" means that a hydrogen atom in a molecule is replaced by a different atom or group, or that a single pair of electrons in an atom in a molecule is replaced by another atom or group, for example, a single pair of electrons in a sulfur atom is replaced by an oxygen atom to form the group in formula 30. TIFF0007866564000057.tif25170 "may be replaced" means that a replacement may occur, but may not occur, and in this specification, this includes the circumstances under which it may or may not occur. The minimum and maximum carbon atom content of a hydrocarbon group is indicated by a prefix, for example, prefix C a~b Alkyl refers to any alkyl group containing "a" to "b" carbon atoms. Therefore, for example, C 1~6 Alkyl refers to an alkyl group containing 1 to 6 carbon atoms. An alkyl group means a saturated hydrocarbon chain having a specific number of member atoms. Alkyl groups may be linear or branched. Typical branched alkyl groups have one, two, or three branched chains. Alkyl groups may optionally be substituted with one or more substituents as defined herein. Examples of alkyl groups include methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, isobutyl and tert-butyl), pentyl (n-pentyl, isopentyl and neopentyl), and hexyl. Alkyl groups may also be part of other groups, such as -O(C) 1~6 It is alkyl. An "alkylene group" refers to a divalent saturated aliphatic hydrocarbon group having a specific number of member atoms. a~b An alkylene group refers to an alkylene group having a to b carbon atoms. Alkylene groups include branched and linear hydrocarbon groups. For example, the term "propylene group" refers to structures such as those in formula 31. Similarly, the term "dimethylbutylene group" refers to any of the structures in formula 32, for example. TIFF0007866564000058.tif19170TIFF0007866564000059.tif24170 The present invention -C 0-4 The alkylene group may be a C0 alkylene group, a C1 alkylene group (e.g., -CH2-), a C2 alkylene group (e.g., -CH2CH2-), a C3 alkylene group, or a C4 alkylene group. In this context, a C0 alkylene group means that the groups are linked by a chemical bond. For example, A-C0 alkylene group-B means that A and B, i.e., groups A and B, are directly linked by a chemical bond.

[0031] The term "carbocyclyl group" in this invention refers to a saturated or non-aromatic partially saturated cyclic group having multiple carbon atoms and no ring-forming heteroatoms, and having one or more rings (condensed, cross-linked, spiro). The term "carbocyclyl group" includes cycloalkenyl groups, such as cyclohexenyl. Examples of monocyclic carbocyclyl groups include cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, cyclooctyl, cyclopentenyl, and cyclohexenyl. Examples of condensed carbocyclyl group systems include bicyclohexyl, bicyclopentyl, bicyclooctyl, etc., and two such bicycloalkyl polycyclic structures, bicyclohexyl of formula 33 and bicyclohexyl of formula 34, are named. TIFF0007866564000060.tif24170TIFF0007866564000061.tif24170 Examples of carbocyclyl groups in the cross-linked carbocyclyl group system include formula 35, adamantanil, etc. Examples of carbocyclyl groups in the spiro-type carbocyclyl group system include formula 36, ​​etc. TIFF0007866564000062.tif30170TIFF0007866564000063.tif32170 The term "carbocyclyl group" further includes the case of a partially saturated cyclic group formed by the condensation of an aromatic ring and a non-aromatic ring, where the linking site can be located at a non-aromatic carbon atom or an aromatic carbon atom, including, for example, 1,2,3,4-tetrahydronaphthylene-5-yl and 5,6,7,8-tetrahydronaphthylene-5-yl. In this invention, "unsaturated" means that the group or molecule contains a carbon-carbon double bond, a carbon-carbon triple bond, a carbon-oxygen double bond, a carbon-sulfur double bond, a carbon-nitrogen triple bond, and the like.

[0032] Furthermore, the term "heterocycloalkyl group" in this invention means a saturated ring or a non-aromatic partially saturated ring having one ring or more rings (condensed, cross-linked, spiro) containing at least one heteroatom, where the heteroatom means a nitrogen atom, oxygen atom, sulfur atom, etc. Generally, it means a monocyclic or polycyclic ring system of monovalent saturated or partially unsaturated rings of multiple ring atoms, containing one, two, or three ring-forming heteroatoms selected from the group consisting of N, O, and S, with the remaining ring-forming atom being carbon. Examples of monocyclic heterocycloalkyl groups include oxetanyl, azetidinyl, pyrrolidinyl, 2-oxo-pyrroridine-3-yl, tetrahydrofuryl, tetrahydrothienyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, piperidinyl, tetrahydropyranil, tetrahydrothiopyranil, piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholin-4-yl, azepanyl, diazepanyl, homopiperazinyl, or oxazepanyl. Examples of condensed heterocycloalkyl groups include 8-aza-bicyclo[3.2.1]octyl, quinuclidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl, and 9-aza-bicyclo[3.3.1]nonyl. Examples of heterocycloalkyl groups in the cross-linked heterocycloalkyl system include formula 37, etc. Examples of heterocycloalkyl groups in the spiro-type heterocycloalkyl system include formula 38, etc. TIFF0007866564000064.tif30170TIFF0007866564000065.tif29170 Examples of partially saturated heterocycloalkyl groups include dihydrofuryl, imidazolinyl, tetrahydropyridyl, or dihydropyranyl. The term “heterocycloalkyl group” further includes the case of a partially saturated cyclic group formed by the condensation of an aromatic ring containing at least one heteroatom and a non-aromatic ring, the linkage site of which can be located at a non-aromatic carbon atom, an aromatic carbon atom, or a heteroatom, including, for example, formula 39. TIFF0007866564000066.tif29170 In this invention, "aryl group" means an aromatic hydrocarbon group having multiple carbon atoms. An aryl group is generally a monocyclic, bicyclic, or tricyclic aryl group having multiple carbon atoms. Furthermore, the term "aryl group" as used herein may also refer to an aromatic substituent which is one aromatic ring or multiple fused aromatic rings. Non-limiting examples include phenyl, naphthyl, or tetrahydronaphthyl. The "heteroaryl group" in this invention means an aromatic unsaturated ring containing at least one heteroatom, where the heteroatom is a nitrogen atom, oxygen atom, sulfur atom, etc. Generally, it is an aromatic monocyclic or bicyclic hydrocarbon containing multiple ring atoms, one or more of which are heteroatoms selected from the group consisting of O, N, and S. Preferably, it has one to three heteroatoms. Representative examples of heteroaryl groups include pyridyl, indolyl, quinoxalinyl, quinolinyl, isoquinolinyl, benzothienyl, benzofuryl, benzothienyl, benzopyranil, benzothiopyranil, furyl, pyrrolyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazolyl, imidazolyl, thienyl, oxadiazolyl, benzimidazolyl, benzothiazolyl, and benzoxazolyl. In this invention, "halogen" means fluorine, chlorine, bromine, or iodine. In this invention, "halogen-substituted alkyl group" means an alkyl group in which one or more hydrogen atoms are substituted with halogens, such as a monofluoromethyl group, a difluoromethyl group, or a trifluoromethyl group. The "deuterium-substituted alkyl group" in this invention means an alkyl group in which one or more hydrogen atoms are substituted with deuterium atoms, for example, a triduteromethyl group.

[0033] In this invention, "-OR", "-NRR", etc., refer to a configuration in which an R group and an oxygen atom or a nitrogen atom are linked by a single bond. In the present invention, the oxygen atom in "-C(O)R", "-S(O)2R", etc., is linked to a carbon atom or a sulfur atom by a double bond, and the R group is linked to the oxygen atom or sulfur atom by a single bond. Furthermore, for example, "-S(O)(NH)R" means that the oxygen atom and nitrogen atom are linked to the sulfur atom by a double bond, and the R group is linked to the sulfur atom by a single bond. In this invention, the group of formula 40 refers to a group in which an oxygen atom and a sulfur atom are linked to a substitution site by a double bond. TIFF0007866564000067.tif21170 Description of the basis according to the present invention TIFF0007866564000068.tif9166 is used to describe the site of the base substitution. In this invention, "deuterium compound" means a molecule or group in which one or more hydrogen atoms are substituted with deuterium atoms, wherein the abundance of deuterium atoms is higher than the natural abundance of deuterium.

[0034] The term "pharmacologically acceptable" means that a carrier, diluent, additive, and / or a salt formed from it is generally compatible with other components that constitute a certain pharmaceutical form, either chemically or physically, and is physiologically compatible with its receptor. The terms "salt" and "pharmacologically acceptable salt" refer to acidic and / or basic salts formed from the above compound or its stereoisomers with inorganic and / or organic acids and bases, including amphoteric salts (internal salts), and further including quaternary ammonium salts, such as alkylammonium salts. These salts can be obtained directly in the final isolation and purification of the compound. Alternatively, these salts can be obtained by mixing the above compound or its stereoisomers with an appropriate amount of acid or base (for example, in equistolic amounts). These salts can be obtained by methods such as forming a precipitate in solution and recovering it by filtration, recovering it after evaporating the solvent, or reacting it in an aqueous medium and then freeze-drying it. The salts in this invention may be hydrochloride, sulfate, citrate, benzenesulfonate, hydrobromide, hydrofluoric acid, phosphate, acetate, propionate, succinate, oxalate, malate, succinate, fumarate, maleate, tartarate, or trifluoroacetate of the compound. In some embodiments, one or more compounds of the present invention can be used in combination with each other. Optionally, the compounds of the present invention can also be used in combination with any other activators for the manufacture of drugs or pharmaceutical compositions that modulate cellular function or treat disease. When a group of compounds is used, they can be administered to a subject simultaneously, separately, or in sequence. Clearly, according to the above-described aspects of the present invention, various other forms of modification, substitution, or alteration can be made in accordance with the ordinary technical knowledge and conventional means in the art, without departing from the above-described basic technical idea of ​​the present invention. The above aspects of the present invention will be described in more detail below by specific embodiments in the form of examples. However, it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples. Any techniques implemented based on the above elements of the present invention are included in the scope of the present invention. [Modes for carrying out the invention]

[0035] The structure of the compound was determined by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The NMR shift (δ) was 10 -6 The values ​​were given in units of ppm. NMR was performed using Bruker Avance III 400 and Bruker Avance 300 NMR spectrometers, with deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD) as the measurement solvents, and tetramethylsilane (TMS) as the internal standard. LC-MS was performed using a Shimadzu LC-MS 2020 (ESI) liquid chromatography-mass spectrometer, HPLC using a Shimadzu LC-20A high-pressure liquid chromatograph, and MPLC (medium-pressure preparative chromatography) using a Gilsong X-281 reverse-phase preparative chromatograph. For thin-layer chromatography, Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates were used, with a specification of 0.4 mm to 0.5 mm for product separation and purification by thin-layer chromatography. 200-300 mesh Yantai Huanghai silica gel was generally used as a carrier for column chromatography. The known starting materials of the present invention can be synthesized using or in accordance with methods known in the art, or can be purchased from companies such as Anegy Chemical, Chengdu Kolon Chemical, Shaoyuan Chemical Technology, and Bailingway Technology.

[0036] The reactions were carried out under a nitrogen atmosphere unless otherwise specified in the examples. The solutions were aqueous solutions unless otherwise specified in the examples. The reaction temperature was room temperature. Unless otherwise specified in the examples, M is the number of moles per liter. Unless otherwise specified in the examples, the HPLC test conditions are as follows: Method A: Column: Bostongreen C18 150mm*4.6mm 5μm, Mobile phase A: 0.05% trifluoroacetic acid aqueous solution, Mobile phase B: 0.05% trifluoroacetic acid in acetonitrile solution, Gradient: Mobile phase B was increased from 5% to 95% over 10 minutes, then maintained at 95% for 5 minutes, Flow rate: 1.5 ml / min, Column temperature: 40°C. Method B: Column: Bostongreen ODS 150mm*4.6mm 5μm, Mobile phase A: 0.01M sodium bicarbonate aqueous solution, Mobile phase B: Acetonitrile, Gradient: Mobile phase B was increased from 5% to 95% over 10 minutes, then maintained at 95% for 5 minutes, Flow rate: 1.5 ml / min, Column temperature: 40°C.

[0037] Example 1: Synthesis of Compound 1 TIFF0007866564000069.tif72170 Step 1: Synthesis of Compounds 1-3: Substrates 1-1 (247.51 mg, 1.29 mmol) and 1-2 (200 mg, 1.29 mmol) were added to a dry necked flask, dissolved with acetic acid (2 mL) and 1,4-dioxane (2 mL), heated to 110°C, stirred overnight, and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following product: product 1-3 (400 mg, 1.29 mmol). Step 2: Synthesis of compounds 1-5: In a dry microwave tube, substrates 1-4 (2 g, 8.44 mmol), dimethyl sulfoximine (786.42 mg, 8.44 mmol), Pd(dba)2 (48.55 mg, 84.43 μmol), BINAP (52.57 mg, 84.43 μmol), and potassium tert-butoxide (1.89 g, 16.89 mmol) were added, dissolved with toluene (10 mL), and reacted under nitrogen protection with microwave at 120°C for 30 minutes, monitored by LC-MS. After the reaction was complete, the organic phase was extracted three times with water and ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: product 1-5 (800 mg, 3.21 mmol). Step 3: Synthesis of Compound 1: In a dry microwave tube, substrates 1-5 (109.92 mg, 441.22 μmol), 1-3 (105 mg, 339.40 μmol), N,N′-diethylethylenediamine (78.88 mg, 678.80 μmol), CuI (64.64 mg, 339.40 μmol), and K2CO3 (65.57 mg, 475.16 μmol) were added, and 1,4-dioxane (3 mL) was added to dissolve the mixture. Under nitrogen protection, the reaction was carried out in a microwave at 110°C and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain: Product 1 (23 mg, 48.16 μmol). 1 H NMR(400MHz,Methanol-d4)δ 8.94(s,1H),8.20(s,1H),7.82(t,J=8.0Hz,1H),7.71(d,J=7.6Hz,1H),7.64(d,J=8.6Hz,2H),7.03(d,J=8.5Hz,2H),6.81(d,J= 7.7Hz,1H),3.80(d,J=12.7Hz,2H),3.61(d,J=12.2Hz,2H),3.47(d,J=8.6Hz,6H),3.29-3.23(m,2H),3.03(s,2H),2.98(s,3H). LCMS(ESI + )m / z:478.3 [M+H] + ,HPLC method A:R T=4.44min, purity: 99.9%.

[0038] Example 2: Synthesis of Compound 2 TIFF0007866564000070.tif42170 Step 1: Synthesis of Compound 2-2: Substrate 2-1 (15 g, 69.43 mmol) was added to a dry necked flask, dissolved in THF (50 mL), and methylmagnesium bromide (20.70 g, 173.59 mmol) was added in an ice bath. The reaction was carried out overnight at room temperature and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 2-2 (15 g, 69.42 mmol). Step 2: Synthesis of Compound 2: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 2-1 (45.40 mg, 210.11 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 2 (10.2 mg, 22.95 μmol). 1 H NMR(400MHz,Methanol-d4)δ 8.99(s,1H),8.30(s,2H),8.01(d,J=7.4Hz,1H),7.71(d,J=8.8Hz,2H),7.56(d,J=7.6Hz,1H),7.05(d,J=8.7Hz, 2H),3.88-3.73(m,2H),3.69-3.56(m,2H),3.29-3.24(m,2H),3.07(d,J=12.2Hz,2H),2.99(s,3H),1.62(s,6H). LCMS(ESI + )m / z:445.4 [M+H] + ,HPLC method A:R T =4.83min, purity: 99.9%.

[0039] Example 3: Synthesis of Compound 3 TIFF0007866564000071.tif73170 Step 1: Synthesis of Compound 3-3: Substrates 3-1 (3g, 12.66 mmol), 3-2 (1.97g, 13.93 mmol), and potassium carbonate (3.50g, 25.33 mmol) were added to a dry, necked flask, dissolved in DMF (10 mL), and reacted overnight at a temperature of 80°C, monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 3-3 (3g, 10.10 mmol). Step 2: Synthesis of compounds 3-4: In a dry, necked flask, substrate 3-3 (3 g, 10.10 mmol) was added, hydrochloric acid (368.11 mg, 10.10 mmol) was added, and the mixture was dissolved in methanol (10 mL). The reaction was carried out overnight at room temperature and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 3-4 (2.4 g, 9.96 mmol). Step 3: Synthesis of compounds 3-5: In a dry, necked flask, substrates 3-4 (400 mg, 2.03 mmol) and p-toluenesulfonic acid (171.46 mg, 995.68 μmol) were added, dissolved with toluene (10 mL), and the mixture was heated to 115°C and reacted overnight, monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: product 3-5 (400 mg, 2.03 mmol). Step 4: Synthesis of compounds 3-6: In a dry, necked flask, substrates 3-5 (350 mg, 1.78 mmol), 1,2-dibromoethane (500.56 mg, 2.66 mmol), tetrabutylammonium sulfate (TBAHS, 120.44 mg, 355.27 μmol), and NaOH (71.05 mg, 1.78 mmol) were added, dissolved with toluene (5 mL), and the mixture was reacted overnight under nitrogen protection and room temperature conditions, monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 3-6 (366 mg, 1.64 mmol). Step 5: Synthesis of Compound 3: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 3-6 (89.05 mg, 399.20 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 3 (30 mg, 66.44 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.90(s,1H),9.79(s,1H),9.05(d,J=0.9Hz,1H),8.34(d,J=0.9Hz,1H),8.11(t,J=7.9Hz,1H),8.02(d,J=8.0Hz,1H),7.71(d,J=8.7Hz,1H),7 .63(d,J=7.6Hz,1H),7.01(d,J=8.6Hz,2H),3.78(d,J=12.7Hz,4H),3.27-3.11(m,2H),3.00-2.91(m,2H),2.88(s,3H),1.81(d,J=4.2Hz,4H). LCMS(ESI + )m / z:452.4 [M+H] + ,HPLC method A:R T =5.54min, purity: 99.9%.

[0040] Example 4: Synthesis of Compound 4 TIFF0007866564000072.tif35170 Step 1: Synthesis of Compound 4-3: Substrates 4-1 (10 g, 49.99 mmol), 4-2 (15.64 g, 109.98 mmol), and potassium acetate (4.90 g, 49.99 mmol) were added to a dry necked flask, dissolved in DMSO (80 mL), stirred overnight at room temperature, and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 4-3 (17 g, 49.67 mmol). Step 2: Synthesis of compound 4-4: In a dry, necked flask, substrate 4-3 (10 g, 49.99 mmol) and potassium carbonate (13.71 g, 99.35 mmol) were added, dissolved in methanol (50 mL), and stirred overnight at room temperature. The mixture was monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 4-4 (13 g, 48.14 mmol). Step 3: Synthesis of Compound 4: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 4-4 (113.48 mg, 420.21 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 4 (60 mg, 120.36 μmol). 1 H NMR(400MHz,Methanol-d4)δ 9.00-8.96(m,1H),8.21(s,1H),7.91-7.76(m,2H),7.75-7.67(m,1H),7.60-7.54(m,1H),7.26-7.18(m,1H),6.85-6.7 6(m,1H),4.58-4.42(m,1H),4.40-4.26(m,1H),3.76(s,2H),3.50(s,6H),3.20(s,1H),3.16-3.12(m,1H),3.07(s,3H). LCMS(ESI + )m / z:499.5 [M+H] + ,HPLC method A:R T =5.85min, purity: 99.7%.

[0041] Example 5: Synthesis of Compound 5 TIFF0007866564000073.tif33170 Step 1: Synthesis of Compound 5-3: In a dry, necked flask, substrate 5-1 (5 g, 28.41 mmol) was added and dissolved in THF (50 mL). NaHMDS (26.05 g, 142.06 mmol) and 5-2 (5.35 g, 56.82 mmol) were added at -17°C under nitrogen protection, and the reaction was carried out at -17°C for 1 hour, monitored by LC-MS. After the reaction was complete, the mixture was diluted with ethyl ether, water was added, and the mixture was extracted three times. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 5-3 (6.18 g, 24.71 mmol). Step 2: Synthesis of Compounds 5-4: In a dry, necked flask, substrate 5-3 (3 g, 11.99 mmol) was added, dissolved in toluene (20 mL), and 1,2-dibromoethane (3.38 g, 17.99 mmol) and tetrabutylammonium bisulfate (TBAHS, 813.23 mg, 2.40 mmol) were added. The mixture was stirred overnight at room temperature and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 5-4 (2.4 g, 8.69 mmol). Step 3: Synthesis of Compound 5: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 5-4 (116.04 mg, 420.21 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 5 (20 mg, 39.63 μmol). 11H NMR (400MHz, DMSO-d6)δ 9.91(s,1H),9.73(s,1H),9.07(s,1H),8.37(s,1H),8.20(d,J=8.1Hz,1H),8.16 -8.07(m,1H),7.71(d,J=9.0Hz,1H),7.62(dd,J=7.5,0.9Hz,1H),7.02(d,J=9.1H z,1H),3.78(d,J=13.1Hz,2H),3.54(d,J=12.1Hz,2H),3.20(s,3H),3.24-3.12( m,2H),2.96(m,2H),2.87(d,J=3.3Hz,3H),1.75-1.67(m,2H),1.63-1.54(m,2H). LCMS(ESI + )m / z:499.5 [M+H] + ,HPLC method A:R T =5.85min, purity: 99.7%.

[0042] Example 6: Synthesis of Compound 6 TIFF0007866564000074.tif40170 Step 1: Synthesis of Compound 6-2: The following compound was obtained by the same synthesis method as in Step 1 of Example 1, except that 6-1 (115.32 mg, 647.01 μmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Compound 6-2 (122 mg, 262.62 μmol). Step 2: Synthesis of Compound 6: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 6-2 (100 mg, 337.47 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 6 (122 mg, 262.62 μmol). 1 H NMR(400MHz,Methanol-d4)δ 7.87(s,2H),7.53(t,J=7.6Hz,2H),7.19(d,J=50.6Hz,3H),6.84(s,1H),6.68(s,1H),3.89(d,J=30.8Hz,4H),3.50-3.34(m,10H). LCMS(ESI + )m / z:465.4 [M+H] +,HPLC method A:R T = 5.07 min, purity: 96.2%.

[0043] Example 7: Synthesis of Compound 7 TIFF0007866564000075.tif71170 Step 1: Synthesis of Compound 7-2: The following compound was obtained by the same synthesis method as in Step 1 of Example 1, except that 7-1 (224.93 mg, 905.81 μmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Compound 7-2 (331 mg, 0.90 mmol). Step 2: Synthesis of compound 7-3: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 7-2 (224.93 mg, 905.81 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 7-3 (100 mg, 187.04 μmol). Step 3: Synthesis of Compound 7: Substrate 7-3 (350 mg, 93.52 μmol) was added to a dry necked flask, dissolved in 4 M HCl / EA (10 mL), and stirred at room temperature for 2 hours, and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 7 (32 mg, 73.65 μmol). 1 H NMR(400MHz,DMSO-d6)δ 10.09(s,1H),9.11(s,1H),9.09(s,1H),8.38(s,1H),7.91(s,1H),7.88-7.81(m,1H),7.67(d,J=7.6Hz,1H),7.55(dd,J=8.4,2 .0Hz,1H),7.19(d,J=8.4Hz,1H),6.69(d,J=7.8Hz,1H),4.29(s,2H),3.49(s,6H),3.41(d,J=5.3Hz,2H),2.96(t,J=6.1Hz,2H). LCMS(ESI + )m / z:435.4 [M+H] + ,HPLC method A:RT =4.41min, purity: 99.6%.

[0044] Example 8: Synthesis of Compound 8 TIFF0007866564000076.tif63170 Step 1: Synthesis of Compound 8-2: Substrate 8-1 (200 mg, 805.41 μmol) was added to a dry necked flask, dissolved in dry THF (10 mL), and lithium aluminum hydride (152.84 mg, 4.03 mmol) was added in an ice bath. The mixture was stirred at room temperature for 30 minutes and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 8-2 (130 mg, 801.33 μmol). Step 2: Synthesis of compound 8-4: The following compound was obtained by the same synthesis method as in Step 1 of Example 1, except that 8-2 (130 mg, 801.33 μmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Compound 8-3 (224 mg, 799.07 μmol). Step 3: Synthesis of Compound 8: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 8-3 (100 mg, 356.73 μmol) was used instead of 1-3 (105 mg, 339.4 μmol) in Step 3: Compound 8 (16 mg, 35.67 μmol). 1 H NMR(400MHz,Methanol-d4)δ 9.00-8.96(m,1H),8.21(s,1H),7.91-7.76(m,2H),7.75-7.67(m,1H),7.60-7.54(m,1H),7.26-7.18(m,1H),6.85-6.7 6(m,1H),4.58-4.42(m,1H),4.40-4.26(m,1H),3.76(s,2H),3.50(s,6H),3.20(s,1H),3.16-3.12(m,1H),3.07(s,3H). LCMS(ESI + )m / z:449.4 [M+H] +,HPLC method A:R T =4.52min, purity: 99.5%.

[0045] Example 9: Synthesis of Compound 9 TIFF0007866564000077.tif69170 Step 1: Synthesis of Compound 9-3: In a dry, necked flask, the substrates p-fluoronitrobenzene (2 g, 14.17 mmol), 9-1 (1.82 g, 14.17 mmol), and DIPEA (2.20 g, 17.01 mmol, 2.96 mL) were added, dissolved in ACN (30 mL), heated to 85°C, stirred for 15 hours, and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following product: 9-3 (3.52 g, 14.12 mmol). Step 2: Synthesis of compound 9-4: In a dry, necked flask, substrate 9-3 (3.52 g, 14.12 mmol) was added, methanol (10 mL) was added, and the mixture was dissolved with stirring. Then Pd / C (170.51 mg, 1.40 mmol) was added, and the mixture was replaced three times with H2. The reaction was carried out at room temperature for 3 hours and monitored by LC-MS. After the reaction was complete, Pd / C was filtered off using diatomaceous earth, the organic phase was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 9-4 (2.1 g, 9.57 mmol). Step 3: Synthesis of Compound 9-6: The following compound was obtained by the same synthesis method as in Step 1 of Example 1, except that 9-4 (123 mg, 560.81 μmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Compound 9-6 (189 mg, 560.13 μmol). Step 4: Synthesis of Compound 9: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 9-6 (189 mg, 560.13 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 9 (20 mg, 39.55 μmol).1 H NMR(400MHz,Chloroform-d)δ 8.94(s,1H),8.20(s,1H),7.80(t,J=7.9Hz,1H),7.68(d,J=7.7Hz,1H),7.62(s,2H),7.05(s,2H),6.78(d,J= 8.1Hz,1H),3.89-3.73(m,2H),3.46-3.43(m,7H),3.43-3.34(m,2H),2.92(s,6H),2.19(s,2H),1.91(s,2H). LCMS(ESI + )m / z:506.5 [M+H] + ,HPLC method A:R T =4.31min, purity: 95.7%.

[0046] Example 10: Synthesis of Compound 10 TIFF0007866564000078.tif55170 Step 1: Synthesis of compound 10-2: In a dry, necked flask, substrate 10-1 (3 g, 18.62 mmol) and iodomethane (8.7 g, 61.43 mmol) were added, dissolved in DMF (20 mL), heated to 70°C, stirred for 15 hours, and monitored by LC-MS. After the reaction was complete, the mixture was stopped with water, ethyl acetate was added and extracted three times, the organic phase was combined, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following product: product 10-2 (3.4 g, 16.73 mmol). Step 2: Synthesis of compound 10-3: In a dry, necked flask, substrate 10-2 (3.3 g, 16.24 mmol) was added and dissolved in H2SO4 (10 mL). HNO3 (1.02 g, 16.24 mmol) was slowly added dropwise over an ice bath, and the mixture was stirred at 0°C for 6 hours, monitored by TLC. After the reaction was complete, the mixture was stopped with water, ethyl acetate was added and extracted three times, the organic phase was combined, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following product: product 10-3 (3.9 g, 15.71 mmol). Step 3: Synthesis of compound 10-4: In a dry, necked flask, substrate 10-3 (270 mg, 1.09 mmol) was added and dissolved in THF (10 mL). BMS (334.82 mg, 4.35 mmol) was slowly added dropwise over an ice bath, the temperature was raised to 70°C, and the mixture was stirred for 24 hours, monitored by LC-MS. After the reaction was complete, the mixture was stopped with saturated sodium sulfite, ethyl acetate was added and extracted three times, the organic phase was combined, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following product: product 10-4 (200 mg, 907.99 μmol). Step 4: Synthesis of compound 10-5: In a dry, necked flask, substrate 10-4 (200 mg, 907.99 μmol) was added, dissolved in ethanol (10 mL), and Pd / C (110.28 mg, 907.99 μmol) was added. After three substitutions with H2, the mixture was stirred with hydrogen for 3 hours and monitored by LC-MS. After the reaction was complete, the mixture was filtered through diatomaceous earth, the organic phase was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following product: product 10-5 (170 mg, 893.40 μmol). Step 5: Synthesis of compound 10-6: The following compound was obtained by the same synthesis method as in Step 1 of Example 1, except that 10-5 (132 mg, 693.70 μmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Compound 10-6 (213 mg, 690.71 μmol). Step 6: Synthesis of compound 10: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 10-6 (100 mg, 324.28 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 10 (27 mg, 54.95 μmol). 1H NMR(400MHz,Chloroform-d)δ 8.98(s,1H),8.21(s,1H),7.87-7.78(m,2H),7.68(d,J=7.3Hz,1H),7.62(dd,J=8.6,2.3Hz,1H),7.46(d,J=8. 7Hz,1H),6.83-6.76(m,1H),4.41(d,J=6.0Hz,2H),3.55-3.45(m,7H),3.40(s,1H),3.11(s,3H),1.46(s,6H). LCMS(ESI + )m / z:477.4 [M+H] + ,HPLC method A:R T = 5.02 min, purity: 96.9%.

[0047] Example 11: Synthesis of Compound 11 TIFF0007866564000079.tif37170 Step 1: Synthesis of Compound 11: Compound 7 (23 mg, crude), (CH3CO)2O (6 mg, 59.0 μmol), and Et3N (12 mg, 118.0 μmol) were added to a dry three-necked flask, dissolved in DCM (1 mL), stirred overnight at room temperature, and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain: Compound 11 (4 mg, 8.40 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.99(s,1H),9.09(s,1H),8.36(s,1H),7.92-7.83(m,2H),7.73-7.65(m,1H),7.47-7.42(m,1H),7.12(d, J=8.4Hz,1H),6.69-6.66(m,1H),4.61(s,2H),3.68(s,2H),3.49(s,6H),2.83(s,2H),2.11(d,J=4Hz,3H). LCMS(ESI + )m / z:477.2 [M+H] + ,HPLC method B:R T =5.77min, purity: 92.1%.

[0048] Example 12: Synthesis of Compound 12 TIFF0007866564000080.tif38170 Step 1: Synthesis of Compound 12-2: In a dry three-necked flask, substrate methylmagnesium bromide (1.0 M in dry THF, 4.4 mL) was added, substrate 12-1 (8.7 g, 61.43 mmol) was dissolved in THF (5 mL), and slowly added dropwise to the three-necked flask at 0°C and under nitrogen protection. The mixture was allowed to slowly return to room temperature and react for 16 hours, monitored by TLC. After the reaction was complete, the system was stopped with water, the pH was adjusted to 6-7 with saturated sodium bicarbonate solution, ethyl acetate was added and extracted three times, the organic phase was combined, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 12-2 (210 mg, 0.99 mmol). 1 H NMR (400MHz, Chloroform-d) δ 7.58(t,J=1.9Hz,1H),7.32(t,J=7.9Hz,2H),7.14(t,J=7.9Hz,1H),2.17(s,1H),1.50(s,6H). Step 2: Synthesis of compound 12: Compound 12 (11 mg, 25.0 μmol) was obtained by the same synthesis method as in step 3 of the synthesis of compound 1, except that 12-2 (100 mg, 470.0 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in step 3. 1 H NMR(400MHz,Chloroform-d)δ 8.77(s,1H),8.30(t,J=1.8Hz,1H),8.20(s,1H),7.93(dt,J=7.2,2.2Hz,1H),7.67(d,J=8.9Hz,2H),7.53-7 .46(m,2H),6.98-6.91(m,2H),3.61(d,J=39.5Hz,4H),3.35(s,2H),3.04(s,2H),2.88(s,3H),1.62(s,6H). LCMS(ESI + )m / z:444.3 [M+H] + ,HPLC method A:R T =5.32min, purity: 82.7%.

[0049] Example 13: Synthesis of Compound 13 TIFF0007866564000081.tif41170 Step 1: Synthesis of Compound 13-2: The following compound was obtained by the same synthesis method as in Example 1, except that 13-1 (120 mg, 0.59 mmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in step 1: compound 13-2 (80 mg, 0.25 mmol). Step 2: Synthesis of compound 13: Following the synthesis method of step 3 in the synthesis of Example 1, the following was obtained by the same synthesis method, except that 13-2 (80 mg, 250.0 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in step 3: Compound 13 (25 mg, 39.91 μmol), which was prepared by the acid method and the product was trifluoroacetate. 1 1H NMR (400MHz, DMSO-d6)δ 9.66(s,1H),9.02(s,1H),8.31(s,1H),7.80(dd,J=8.8,7.0Hz,1H),7.72-7 .57(m,3H),6.76-6.62(m,3H),4.62(s,1H),4.34(d,J=2.3Hz,1H),3.69-3.6 1(m,2H),3.48(d,J=1.7Hz,6H),3.28(d,J=10.9Hz,1H),3.09(dt,J=11.2,2 .9Hz,1H),2.88(d,J=5.0Hz,3H),2.44-2.31(m,1H),2.15(d,J=11.3Hz,1H). LCMS(ESI + )m / z:490.5 [M+H] + ,HPLC method A:R T =4.56min, purity: 96.4%.

[0050] Example 14: Synthesis of Compound 14 TIFF0007866564000082.tif71170 Step 1: Synthesis of Compound 14-3: In a dry three-necked flask, substrates 14-1 (182 mg, 1.42 mmol), 14-2 (200 mg, 1.29 mmol), and K2CO3 (534 mg, 3.87 mmol) were added, dissolved in DMF (10 mL), and reacted under N2 protection at 90°C for 3 hours, monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was used directly in the next step without purification to obtain: 14-3 (100 mg, crude). LC-MS (ESI + )m / z:264.3 [M+H] + . Step 2: Synthesis of compound 14-4: In a dry, necked flask, substrate 14-3 (100 mg, 43.0 μmol) was added, dissolved in MeOH (5 mL), Pd / C (30 mg) was added, and after three substitutions with H2, the mixture was stirred at room temperature for 30 minutes and monitored by LC-MS. After the reaction was complete, the mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain the following: crude product 14-4 (109 mg, crude), LC-MS (ESI + )m / z:234.2 [M+H] + . Step 3: Synthesis of Compound 14-5: The following was obtained by following the synthesis method of Step 1 in Example 1, except that 14-4 (109 mg, 0.468 mmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 14-5 (53 mg, 0.151 mmol). LCMS (ESI + )m / z:352.4 [M+H] + . Step 4: Synthesis of compound 14: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 14-4 (53 mg, 151.0 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 14 (11.9 mg, 22.93 μmol). 1H NMR(400MHz,DMSO-d6)δ 9.79(s,1H),9.03(d,J=3.6Hz,1H),8.32(s,1H),7.81(d,J=8Hz,1H),7.77 (d,J=10.4Hz,1H),7.68(d,J=7.6Hz,1H),7.46-7.44(m,1H),6.98(d,J=8. 4Hz,1H),6.6(d,J=12.8Hz,1H),3.48(s,1H),3.47(s,6H),3.05(d,J=10.8 Hz,4H),2.24(d,J=3.6Hz,9H),1.85(d,J=10.8Hz,2H),1.57-1.53(m,2H). LCMS(ESI + )m / z:520.3 [M+H] + ,HPLC method B:R T= 4.75min, purity: 76.0%.

[0051] Example 15: Synthesis of Compound 15 TIFF0007866564000083.tif34170 Step 1: Synthesis of Compound 15-2: The following was obtained by the same synthesis method as in Step 1 of Example 1, except that 15-1 (50 mg, 0.217 mmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 15-2 (35 mg, 0.101 mmol). LCMS (ESI + )m / z:349.2 [M+H] + . Step 2: Synthesis of compound 15: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 15-2 (35 mg, 101.0 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 15 (11.9 mg, 22.93 μmol). 1H NMR(400MHz,DMSO-d6)δ 9.86(s,1H),9.07(s,1H),8.34(s,1H),7.79(t,J=7.6Hz,1H),7.65(d,J=8.4Hz,2H),7.61(d,J=7.6Hz,1H),7.19(d,J=8.4Hz,2H) ),6.66(d,J=8.0Hz,1H),3.44(s,6H),3.11(s,1H),3.01-2.87(m,2H),2.77-2.66(m,4H),2.30-2.28(m,1H),1.98-1.88(m,4H). LCMS(ESI + )m / z:517.2 [M+H] + ,HPLC method B:R T = 4.84 min, purity: 85.7%.

[0052] Example 16: Synthesis of Compound 16 TIFF0007866564000084.tif34170 Step 1: Synthesis of Compound 16-2: The following was obtained by following the same synthesis method as in Step 1 of Example 1, except that 16-1 (50 mg, 0.217 mmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 16-2 (98 mg, 0.302 mmol). LCMS (ESI + )m / z:324.4 [M+H] + . Step 2: Synthesis of compound 16: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 16-2 (98 mg, 303.0 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 16 (22.4 mg, 45.53 μmol). 1H NMR(400MHz,DMSO-d6)δ 9.82(s,1H),9.05(d,J=3.6Hz,1H),8.33(s,1H),7.82-7.77(m,2H),7.68(d,J=7.6Hz,1H),7.47(dd,J=8.4Hz,1H ),7.00(d,J=8.4Hz,1H),6.66(d,J=7.6Hz,1H),3.47(s,6H),2.84(s,4H),2.59(s,3H),2.29(s,4H),2.26(s,3H). LCMS(ESI + )m / z:492.2 [M+H] + ,HPLC method B:R T= 6.50min, purity: 92.9%.

[0053] Example 17: Synthesis of Compound 17 TIFF0007866564000085.tif65170 Step 1: Synthesis of Compound 17-3: Following the synthesis method of Step 1 in Example 14, the following was obtained by the same synthesis method, except that 17-1 (200 mg, 0.952 mmol) was used instead of 14-1 (182 mg, 1.42 mmol) in Step 1, and 17-2 (105 mg, 1.05 mmol) was used instead of 14-2 (200 mg, 1.29 mmol): Product 17-3 (400 mg, crude). LCMS (ESI + )m / z:290.0 [M+H] + . Step 2: Synthesis of compound 17-4: In a dry, necked flask, substrate 17-3 (100 mg, 0.346 mmol) was added and dissolved in EtOH (5 mL). Fe powder (97 mg, 1.73 mmol) and AcOH (0.1 mL) were added, the mixture was heated to 80°C, stirred for 1 hour, and monitored by LC-MS. After the reaction was complete, the mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain the following: product 17-4 (66 mg, crude), LC-MS (ESI + )m / z:260.1 [M+H] + . Step 3: Synthesis of compound 17-5: The following was obtained by following the same synthesis method as in Step 1 of Example 1, except that 17-4 (66 mg, 0.255 mmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 17-5 (57 mg, 0.151 mmol). LCMS (ESI + )m / z:378.1 [M+H] + . Step 4: Synthesis of compound 17: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 17-5 (57 mg, 151.0 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 17 (7.5 mg, 13.74 μmol). 1 H NMR(400MHz,DMSO-d6)δ 10.34(s,1H),9.16(d,J=3.6Hz,1H),8.43(s,1H),8.02(s,2H),7.83-7.79(m,2H),7 .64(d,J=8.0Hz,1H),6.70(d,J=8.0Hz,1H),3.49(s,8H),3.03(s,5H),2.53(s,4H). LCMS(ESI + )m / z:546.1 [M+H] + ,HPLC method B:R T =7.80min, purity: 65.4%.

[0054] Example 18: Synthesis of Compound 18 TIFF0007866564000086.tif38170 Step 1: Synthesis of Compound 18-2: The following was obtained by following the same synthesis method as in Step 1 of Example 1, except that 18-1 (27 mg, 141.89 μmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 18-2 (40 mg, 116.74 μmol). LCMS (ESI + )m / z:309.3 [M+H] + . Step 2: Synthesis of compound 18: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that HGC041-02 (60 mg, 194.57 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 18 (23 mg, 47.78 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.88(s,1H),9.08(s,1H),8.34(s,1H),7.91-7.77(m,1H),7.71(d,J=8.6Hz,2H),7.62(d,J=7.5Hz,1H),7.20(dd,J=8.9,2.4Hz ,2H),6.70-6.61(m,1H),3.46(s,6H),2.90-2.82(m,2H),2.47-2.35(m,2H),2.19(s,3H),2.00-1.90(m,2H),1.75-1.59(m,3H). LCMS(ESI + )m / z:477.3 [M+H] + ,HPLC method B:R T =5.74min, purity: 99.0%.

[0055] Example 19: Synthesis of Compound 19 TIFF0007866564000087.tif40170 Step 1: Synthesis of Compound 19-2: The following was obtained by following the synthesis method of Step 1 in Example 1, except that 19-1 (100 mg, 0.478 mmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 19-2 (156 mg, 0.477 mmol). LCMS (ESI + )m / z:328.4 [M+H] + . Step 2: Synthesis of compound 19: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 19-2 (80 mg, 245.0 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 19 (14 mg, 28.27 μmol). 1H NMR(400MHz,DMSO-d6)δ 10.00(s,1H),9.03(s,1H),8.36(s,1H),7.79(t,J=8.0Hz,2H),7.61(d,J=8.0Hz,1H),7.44(t,J=6.4Hz ,1H),7.02(d,J=9.6Hz,1H),6.68(d,J=8.0Hz,1H),3.48(s,6H),3.38(s,4H),2.97(s,4H),2.23(s,3H). LCMS(ESI + )m / z:496.1 [M+H] + ,HPLC method B:R T =6.15min, purity: 88.7%.

[0056] Example 20: Synthesis of Compound 20 TIFF0007866564000088.tif42170 Step 1: Synthesis of Compound 20-2: The following was obtained by following the synthesis method of Step 1 in Example 1, except that 20-1 (100 mg, 0.365 mmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 20-2 (168 mg, 0.429 mmol). LCMS (ESI + )m / z:393.5 [M+H] + . Step 2: Synthesis of compound 20: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 20-2 (80 mg, 204.0 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 20 (20.6 mg, 36.79 μmol). 1H NMR(400MHz,DMSO-d6)δ 9.71(s,1H),9.02(s,1H),8.31(s,1H),7.81(t,J=8.0Hz,1H),7.64-7. 59(m,3H),6.92(d,J=8.8Hz,2H),6.65(d,J=8.0Hz,1H),3.65(d,J=8.0H z,2H),3.46(s,6H),2.61(t,J=11.6Hz,2H),2.51(d,J=2.0Hz,5H),2.2 9-2.25(m,4H),2.14(s,3H),1.83(d,J=12.0Hz,2H),1.54-1.47(m,2H). LCMS(ESI + )m / z:561.3 [M+H] + ,HPLC method B:R T =5.57min, purity: 87.8%.

[0057] Example 21: Synthesis of Compound 21 TIFF0007866564000089.tif40170 Step 1: Synthesis of Compound 21: The following compound was obtained by following the same synthesis method as in Step 3 of Example 1, except that 16-2 (74 mg, 229.0 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) and 2-1 (41 mg, 191.0 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 21 (20.6 mg, 15.72 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.91(s,1H),9.07(s,1H),8.34(s,1H),8.05(t,J=7.6Hz,1H),7.98(d,J=8.8Hz,1H),7.75-7.70(m,2H),7.6 2(d,J=2.4Hz,1H),6.99(d,J=8.8Hz,1H),5.34(s,1H),2.95(s,7H),2.61(s,4H),2.56(s,3H),1.51(s,6H). LCMS(ESI + )m / z:459.2 [M+H] + ,HPLC method B:R T= 7.24min, purity: 85.1%.

[0058] Example 22: Synthesis of Compound 22 TIFF0007866564000090.tif38170 Step 1: Synthesis of Compound 22-2: Following the synthesis method of Step 1 in Example 1, the following was obtained by the same synthesis method except that 22-1 was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 22-2 (50 mg, 147.32 μmol). LCMS (ESI + )m / z:340.4 [M+H] + . Step 2: Synthesis of compound 22: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 22-2 (50 mg, 147.32 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 22 (40 mg, 78.8 μmol). 1 H NMR(400MHz,Chloroform-d)δ 8.88(s,1H),8.32(d,J=9.7Hz,1H),8.07(s,1H),7.76-7.67(m,2H),6.81(d,J=7.7Hz,1H),6. 60-6.55(m,2H),3.91(s,3H),3.50(s,6H),3.30-3.18(m,4H),2.77-2.67(m,4H),2.45(s,3H).

[0059] Example 23: Synthesis of Compound 23 TIFF0007866564000091.tif38170 Step 1: Synthesis of Compound 23-2: Following the synthesis method of Step 1 in Example 1, the following was obtained by the same synthesis method except that 23-1 was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 23-2 (100 mg, 294.64 μmol). LCMS (ESI + )m / z:340.4 [M+H] + . Step 2: Synthesis of compound 23: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 23-2 (100 mg, 294.64 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 23 (70 mg, 137.9 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.87(s,1H),9.05(s,1H),8.33(s,1H),7.99(s,1H),7.87-7.72(m,2H),7.55(d,J=8.7Hz,1H),7.04(d,J=8.7Hz,1H),6.65(d,J=8 .5Hz,1H),5.76(s,1H),5.14-5.01(m,1H),4.58(d,J=5.1Hz,2H),3.48(s,6H),2.87-2.81(m,4H),2.53-2.50(m,4H),2.25(s,3H), 1 H NMR(400MHz,DMSO-d6+D2O)δ 9.05(s,1H),8.33(s,1H),7.95(s,1H),7.83(t,J=7.9Hz,1H),7.74(d,J=7.7Hz,1H),7.54(dd,J=8.6,2.7Hz,1H),7.07(d,J= 8.7Hz,1H),6.68(d,J=7.9Hz,1H),5.69(s,1H),4.59(s,2H),3.47(s,6H),2.87-2.81(m,4H),2.53-2.50(m,4H),2.25(s,3H).

[0060] Example 24: Synthesis of Compound 24 TIFF0007866564000092.tif40170 Step 1: Synthesis of Compound 24-2: The following was obtained by following the synthesis method of Step 1 in Example 1, except that 24-1 (65 mg, 2.57 mmol) was used instead of 1-2 (200 mg, 1.29 mmol) in Step 1: Product 24-2 (65 mg, 0.172 mmol). LCMS (ESI + )m / z:378.2 [M+H] + . Step 2: Synthesis of compound 24: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 24-2 (65 mg, 0.172 mmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 24 (31.8 mg, 58.35 μmol). 1 H NMR(400MHz,DMSO-d6)δ 10.14(s,1H),9.15(s,1H),7.87(s,1H),7.61(d,J=5.4Hz,3H),6.94(d,J=7.2Hz ,2H),6.74(d,J=7.8Hz,1H),3.45(s,6H),3.09(s,4H),2.46(s,4H),2.22(s,3H). LCMS(ESI + )m / z:546.2 [M+H] + ,HPLC method B:R T =7.51min, purity: 95.3%.

[0061] Example 25: Synthesis of Compound 25 TIFF0007866564000093.tif72170 Step 1: Synthesis of Compound 25-2: In a dry, necked flask, substrate 25-1 (261 mg, 947.90 μmol) and formaldehyde (85.38 mg, 2.84 mmol) were added, dissolved in methanol (10 mL) and acetic acid (0.1 mL), and stirred at room temperature for 1 hour. Then, NaCNBH3 (148.92 mg, 2.37 mmol) was added, the temperature was raised to 50°C, and the mixture was stirred for 5 hours, and monitored by LC-MS. After the reaction was complete, the organic phase was concentrated under reduced pressure, extracted three times with water and ethyl acetate, and the organic phase was combined, washed with saturated brine, and dried over anhydrous sodium sulfate to obtain the following: Crude product 25-2 (260 mg, 898.50 μmol). LC-MS (ESI + )m / z:290.3 [M+H] + . Step 2: Synthesis of compound 25-3: In a dry, necked flask, substrate 25-2 (260 mg, 898.50 μmol) was added, dissolved in methanol (10 mL), and Pd / C (35.25 mg, 290.28 μmol) was added. After three substitutions with H2, the reaction was carried out at room temperature for 3 hours and monitored by LC-MS. After the reaction was complete, the mixture was filtered through diatomaceous earth, the organic phase was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 25-3 (231 mg, 801.50 μmol). LC-MS (ESI + )m / z:260.4 [M+H] + . Step 3: Synthesis of compound 25-4: The following was obtained by following the same synthesis method as in Step 1 of Example 1, except that 25-3 (231 mg, 801.50 μmol) was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 25-4 (60 mg, 158.95 μmol). LCMS (ESI + )m / z:378.5 [M+H] + . Step 4: Synthesis of compound 25: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 25-4 (60 mg, 158.95 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 25 (35 mg, 51.31 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.70(s,1H),9.02(s,1H),8.30(s,1H),7.81(t,J=7.9Hz,1H),7.62(dd,J=14.0,8.3Hz,3H),6.92(d,J=9.0Hz,2H),6.65(d,J LCMS (ESI + )m / z:545.7 [M+H] + ,HPLC method B:R T = 6.09 min, purity: 81.9%.

[0062] Example 26: Synthesis of Compound 26 TIFF0007866564000094.tif39170 Step 1: Synthesis of Compound 26-2: Following the synthesis method of Step 1 in Example 1, the following was obtained by the same synthesis method except that 26-1 was used instead of 1-1 (247.51 mg, 1.29 mmol) in Step 1: Product 26-2 (100 mg, 451.88 μmol). LCMS (ESI + )m / z:340.4 [M+H] + . Step 2: Synthesis of compound 26: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 26-2 (60 mg, 176.79 μmol) was used instead of 1-3 (105 mg, 339.40 μmol) in Step 3: Compound 26 (31 mg, 59.85 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.83(s,1H),9.06(s,1H),8.33(s,1H),7.77(t,J=7.7Hz,1H),7.62-7.56(m,2H),7.22(d,J=8.4Hz,1H),6.85(d,J =8.5Hz,1H),6.67(d,J=8.0Hz,1H),3.70(s,3H),3.45(s,6H),2.94-2.91(m,4H),2.46-2.43(m,4H),2.21(s,3H). LCMS(ESI + )m / z:508.2 [M+H] + ,HPLC method B:R T =5.64min, purity: 98.0%.

[0063] Example 27: Synthesis of Compound 27 TIFF0007866564000095.tif68170 Step 1: Synthesis of compounds 27-A1 and 27-B1: In a dry, necked flask, substrate 27-1 (35 mg, 99.88 μmol), Cs2CO3 (97 mg, 299.64 μmol), and DMF (5 mL) were added and stirred for 5 minutes. Then, iodomethane (40.10 mg, 282.52 μmol) was added, and the temperature was raised to 90°C to react, which was monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure, and the residue was purified by medium-pressure liquid chromatography (base method) to obtain: 27-A1 (18 mg, 19.23% yield) or 27-B1 (26 mg, 27.78% yield), LCMS(E+) m / z: 365.3 [M+H]. + . Step 2: Synthesis of compound 27-A: In a dry, necked flask, substrate 27-A1 (18 mg, 49.39 μmol) and tetrahydrofuran (2 mL) were added and dissolved with stirring. Then, m-CPBA (10.23 mg, 59.27 μmol) was added, and the reaction was carried out at room temperature for 1 hour, monitored by LC-MS. After the reaction was complete, DIPEA (33.39 mg, 258.36 μmol) was added, and after stirring for 10 minutes, 1-1 (20.11 mg, 105.14 μmol) was added, and the reaction was carried out at room temperature, monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure, and the residue was purified by medium-pressure liquid chromatography (base method) to obtain 27-A (3 mg, 5.91 μmol). 1 H NMR(400MHz,DMSO-d6)δ 8.79(s,1H),7.85(d,J=6.8Hz,1H),7.58(s,2H),7.33(d,J=8.0Hz,1H),6.92(d,J=9.2Hz,2 H),6.61(d,J=8.4Hz,1H),3.43(s,3H),3.36(s,6H),3.10(s,4H),2.53(s,4H),2.24(s,3H). 1 1H NMR (400MHz, DMSO-d 6、D2O)δ 8.79(s,1H),7.85(s,1H),7.57(s,2H),7.33(d,J=7.8Hz,1H),6.94(d,J=8.5Hz,2H),6 .66(d,J=7.9Hz,1H),3.44(s,3H),3.35(s,6H),3.11(s,4H),2.49(s,4H),2.24(s,3H). LCMS(ESI + )m / z:508.2 [M+H] + ,HPLC method B:R T= 5.36min, purity: 84.4%. Step 3: Synthesis of compound 27-B: In a dry, necked flask, substrate 27-B1 (26 mg, 71.34 μmol) was added, tetrahydrofuran (2 mL) was added and dissolved with stirring, then m-CPBA (14.77 mg, 85.61 μmol) was added, and the reaction was carried out at room temperature for 1 hour, monitored by LC-MS. After the reaction was complete, DIPEA (40.81 mg, 315.77 μmol) was added, stirred for 10 minutes, then 1-1 (30.17 mg, 157.71 μmol) was added, and the reaction was carried out at room temperature, monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure, and the residue was purified by medium-pressure liquid chromatography (base method) to obtain 27-B (4 mg, 7.89 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.76(s,1H),8.88(s,1H),7.75(s,1H),7.68(s,1H),7.62-7.61(m,2H),6.95(d,J=6.0Hz,2 H),6.55(d,J=6.0Hz,1H),4.06(s,3H),3.50(s,6H),3.12(s,4H),2.56(s,4H),2.32(s,3H). 1 1H NMR (600MHz, DMSO-d 6, D2O)δ 8.86(s,1H),7.77(t,J=7.0Hz,1H),7.68(d,J=7.2Hz,1H),7.60(d,J=6.6Hz,2H),6.97(d,J=7.2 Hz,2H),6.59(d,J=7.2Hz,1H),4.07(s,3H),3.50(s,6H),3.14(s,4H),2.65(s,4H),2.31(s,3H). LCMS(ESI+ )m / z:508.2 [M+H] + ,HPLC method B:R T= 6.54min, purity: 96.5%.

[0064] Example 28: Synthesis of Compound 28 TIFF0007866564000096.tif39170 Step 1: Synthesis of compound 28-2: In a dry microwave tube, substrate 28-1 (500 mg, 2.60 mmol), dimethyl sulfoximine (169.41 mg, 1.82 mmol), Xantphos (75.17 mg, 129.91 μmol), Pd2(dba)3 (47.58 mg, 51.96 μmol), and Cs2CO3 (880.41 mg, 2.70 mmol) were added, and 1,4-dioxane (30 mL) was added to dissolve the mixture. Under nitrogen protection, the mixture was stirred under microwave at 110°C for 12 hours and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 28-2 (113.4 mg, 217.97 μmol). LC-MS (ESI + )m / z:205.1 [M+H] + . Step 2: Synthesis of compound 28: In a dry microwave tube, substrates 1-3 (100 mg, 323.24 μmol), 28-2 (55.13 mg, 269.37 μmol), t-BuOK (30.23 mg, 269.37 μmol), Pd2(dba)3 (8.63 mg, 9.43 μmol), and Xantphos (15.59 mg, 26.94 μmol) were added, and 1,4-dioxane (3 mL) was added to dissolve the substances. The mixture was stirred under nitrogen protection and microwaved at 130°C for 10 hours, and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by recrystallization to obtain product 28 (113.4 mg, 217.97 μmol). 1H NMR(400MHz,DMSO-d6)δ 10.84(s,1H),10.03(s,1H),9.05(s,1H),8.36(s,1H),8.23(d,J=5.4Hz,1H),7.73(d,J=6.6Hz,3H), 7.05(d,J=9.0Hz,2H),3.77(s,2H),3.44(s,6H),3.17(s,2H),3.09(s,2H),2.81(s,3H),2.53(s,2H). LCMS(ESI + )m / z:478.2 [M+H] + ,HPLC method B:R T= 5.86min, purity: 91.8%.

[0065] Example 29: Synthesis of Compound 29 TIFF0007866564000097.tif35170 Step 1: Synthesis of Compound 29-2: In a dry three-necked flask, substrate 29-1 (500 mg, 2.91 mmol) was added, dissolved in THF (10 mL), and replaced three times with N2. Methylmagnesium bromide (764 mg, 6.41 mmol) was added dropwise at 0°C, and the mixture was stirred at room temperature for 1 hour, monitored by LC-MS. After the reaction was complete, the mixture was stopped with saturated ammonium chloride solution, extracted three times with water and ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. The mixture was then concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 29-2 (165 mg, 0.965 mmol). LC-MS (ESI + )m / z:172.2 [M+H] + . Step 2: Synthesis of compound 29: The following compound was obtained by the same synthesis method as in Step 2 of Example 28, except that 29-2 (38 mg, 0.22 mmol) was used instead of 28-2 (55.13 mg, 269.37 μmol) in Step 2: Compound 29 (18 mg, 4.054 μmol). 1H NMR(400MHz,DMSO-d6)δ 10.02(s,1H),9.10(s,1H),8.68(d,J=5.4Hz,1H),8.61(s,1H),8.44(s,1H),8.20(S,1H),7.76(d,J= 6.6Hz,2H),7.06(d,J=8.4Hz,2H),5.44(s,1H),3.17(s,4H),2.54(s,4H),2.29(s,3H),1.57(s,6H). LCMS(ESI + )m / z:445.2 [M+H] + ,HPLC method B:R T = 6.65 min, purity: 92.9%.

[0066] Example 30: Synthesis of Compound 30 TIFF0007866564000098.tif36170 Step 1: Synthesis of compound 30-2: Following the synthesis method of Step 1 in Example 28, the following was obtained by the same synthesis method, except that 30-1 (500 mg, 2.12 mmol) was used instead of 28-1 (500 mg, 2.60 mmol) in Step 1: Product 30-2 (340 mg, 1.37 mmol). LCMS (ESI + )m / z:249.0 [M+H] + . Step 2: Synthesis of compound 30: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 30-2 (67 mg, 0.27 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 30 (22.8 mg, 44.17 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.81(s,1H),9.02(s,1H),8.27(s,1H),7.82-7.80(m,1H),7.75(s,1H),7.69(d,J=5.6Hz,2H),7.38(t,J =5.6Hz,1H),6.95-6.92(m,3H),3.26(s,6H),3.09(t,J=2.8Hz,4H),2.47(t,J=2.8Hz,4H),2.23(s,3H). LCMS(ESI + )m / z:477.1 [M+H]+ ,HPLC method B:R T =6.11min, purity: 95.9%.

[0067] Example 31: Synthesis of Compound 31 TIFF0007866564000099.tif37170 Step 1: Synthesis of compound 31-2: Following the synthesis method of Step 1 in Example 28, the following was obtained by the same synthesis method, except that 31-1 (300 mg, 1.27 mmol) was used instead of 28-1 (500 mg, 2.60 mmol) in Step 1: Product 31-2 (310 mg, 1.24 mmol). LCMS (ESI + )m / z:249.0 [M+H] + . Step 2: Synthesis of compound 31: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 31-2 (40 mg, 0.16 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 31 (25.3 mg, 52.50 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.88(s,1H),9.06(s,1H),9.04(s,1H),8.34(s,1H),8.17(s,1H),8.06(s,1H),7.65(d,J =6.0Hz,2H),6.93(d,J=6.0Hz,2H),3.33(s,6H),3.11(s,4H),2.52(s,4H),2.26(s,3H). LCMS(ESI + )m / z:478.1 [M+H] + ,HPLC method B:R T= 5.46min, purity: 98.9%.

[0068] Example 32: Synthesis of Compound 32 TIFF0007866564000100.tif35170 Step 1: Synthesis of Compound 32-2: The following was obtained by following the synthesis method of Step 1 in Example 29, except that 32-1 (300 mg, 1.39 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Product 32-2 (374 mg, crude). LCMS (ESI + )m / z:217.0 [M+H] + . Step 2: Synthesis of compound 32: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 32-2 (52 mg, 0.24 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 32 (9.8 mg, 21.65 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.89(s,1H),9.24(s,1H),9.05(s,1H),8.66(d,J=1.2Hz,1H),8.62(s,1H),8.36(s,1H),7.66(d,J=6.0H z,2H),6.93(d,J=6.0Hz,2H),5.41(s,1H),3.10(d,J=2.8Hz,4H),2.52(s,4H),2.25(s,3H),1.54(s,6H). LCMS(ESI + )m / z:445.2 [M+H] + ,HPLC method B:R T= 5.98 min, purity: 98.2%.

[0069] Example 33: Synthesis of Compound 33 TIFF0007866564000101.tif37170 Step 1: Synthesis of compound 33-2: Following the synthesis method of Step 1 in Example 28, the following was obtained by the same synthesis method, except that 33-1 (300 mg, 1.18 mmol) was used instead of 28-1 (500 mg, 2.60 mmol) in Step 1: Product 33-2 (230 mg, 0.864 mmol). LCMS (ESI + )m / z:266.1 [M+H] + . Step 2: Synthesis of compound 33: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 33-2 (60 mg, 0.23 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 33 (5.4 mg, 10.59 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.73(s,1H),9.02(s,1H),8.29(s,1H),7.59(d,J=8.4Hz,2H),7.32-7.29(m,1H),7.20(t,J=7.8Hz,1H),7 .16(t,J=6.0Hz,1H),6.83(d,J=9.0Hz,2H),3.32(s,6H),3.05(t,J=4.2Hz,4H),2.46(s,4H),2.23(s,3H). LCMS(ESI + )m / z:495.2 [M+H] + , HPLC method B: RT=5.62min, purity: 96.1%.

[0070] Example 34: Synthesis of Compound 34 TIFF0007866564000102.tif35170 Step 1: Synthesis of compound 34-2: Following the synthesis method of Step 1 in Example 29, the following was obtained by the same synthesis method, except that 34-1 (300 mg, 1.39 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Product 34-2 (330 mg, crude). LCMS (ESI + )m / z:216.1 [M+H] + . Step 2: Synthesis of compound 34: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 34-2 (59 mg, 0.272 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 34 (30.7 mg, 66.91 μmol). 1H NMR(400MHz,DMSO-d6)δ 9.84(s,1H),9.03(s,1H),8.57(s,1H),8.31(s,1H),8.15(s,1H),7.78(d,J=7.2Hz,2H),7.51(s,1H),6. 91(d,J=9.0Hz,2H),5.43(s,1H),3.07(t,J=4.2Hz,4H),2.46(t,J=4.2Hz,4H),2.22(s,3H),1.49(s,6H). LCMS(ESI + )m / z:445.3 [M+H] + ,HPLC method B:R T =5.60min, purity: 96.7%.

[0071] Example 35: Synthesis of Compound 35 TIFF0007866564000103.tif35170 Step 1: Synthesis of Compound 35-2: Following the synthesis method of Step 1 in Example 29, the following was obtained by the same synthesis method, except that 35-1 (400 mg, 1.86 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Product 35-2 (360 mg, crude). TLC (PE / EA = 3 / 1) showed that the starting materials had completed their reaction and a new point had been formed. Step 2: Synthesis of compound 35: The following compound was obtained by following the synthesis method of step 3 in Example 1, except that 35-2 (52 mg, 0.242 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in step 3, and 24-2 (97 mg, 0.259 mmol) was used instead of 1-3 (105 mg, 339.40 μmol) in step 3: Compound 35 (4.6 mg, 7.81 μmol). 1H NMR(400MHz,DMSO-d6)δ 10.19(s,1H),9.16(s,1H),8.57(s,1H),8.21(s,1H),7.91(s,1H),7.68(d,J=3.6Hz,2H),7.57-7.53(m,2H) ,6.94(d,J=9.0Hz,2H),5.25(s,1H),3.09(t,J=4.2Hz,4H),2.46(t,J=4.8Hz,4H),2.23(s,3H),1.50(s,6H). LCMS(ESI + )m / z:512.2 [M+H] + ,HPLC method B:R T =8.86min, purity: 87.4%.

[0072] Example 36: Synthesis of Compound 36 TIFF0007866564000104.tif35170 Step 1: Synthesis of Compound 36: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 36-1 (37 mg, 0.162 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 36 (32.5 mg, 64.85 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.92(s,1H),9.36(s,1H),9.08(s,1H),9.02(s,1H),8.69(d,J=8.4Hz,1H),8.54(d,J=5.4Hz,1H),8.39(s,1H),8.20(d,J=9.0 Hz,1H),7.91(d,J=6.0Hz,1H),7.70(d,J=7.8Hz,2H),7.01(d,J=9.0Hz,2H),3.14(d,J=4.8Hz,4H),2.52(s,4H),2.24(s,3H). LCMS(ESI + )m / z:437.2 [M+H] + ,HPLC method B:R T= 7.63min, purity: 87.1%.

[0073] Example 37: Synthesis of Compound 37 TIFF0007866564000105.tif39170 Step 1: Synthesis of Compound 37: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 37-1 (55 mg, 0.259 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 37 (5.9 mg, 13.11 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.93(s,1H),9.52(s,1H),9.07(s,1H),8.96(s,1H),8.41(dd,J=9.0Hz,1H),8.38(d,J=7.2H z,2H),7.73(d,J=7.8Hz,2H),6.98(d,J=9.0Hz,2H),3.19(s,4H),2.79(s,3H),2.52(s,4H). LCMS(ESI + )m / z:443.1 [M+H] + ,HPLC method B:R T = 7.47 min, purity: 98.3%.

[0074] Example 38: Synthesis of Compound 38 TIFF0007866564000106.tif35170 Step 1: Synthesis of Compound 38: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 38-1 (37 mg, 0.162 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 38 (28.7 mg, 53.80 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.88(s,1H),9.04(s,1H),8.72(s,1H),8.31(d,J=9.0Hz,2H),8.10(s,1H),7.75(d,J=7.8Hz,2H),7.53(d,J=8.4 Hz,1H),7.00(d,J=8.6Hz,2H),3.45-3.43(m,2H),3.10(s,4H),2.99(t,J=6.0Hz,2H),2.52(s,4H),2.27(s,3H). LCMS(ESI + )m / z:455.2 [M+H] + ,HPLC method B:R T =6.25min, purity: 85.2%.

[0075] Example 39: Synthesis of Compound 39 TIFF0007866564000107.tif57170 Step 1: Synthesis of compound 39-2: In a dry necked flask, 30 mL of ethyl acetate solution of CuBr2 (16.70 g, 72.00 mmol) was added. At room temperature, 30 mL of trichloromethane solution of substrate 39-1 (5.20 g, 24.00 mmol) was slowly added dropwise to the reaction mixture. After stirring for 30 minutes, the mixture was transferred to an oil bath at 80°C and the reaction continued, monitored by TLC. After the reaction was complete, the reaction mixture was filtered, the mother liquor was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain product 39-2 (7.00 g, 23.90 mmol). Step 2: Synthesis of compound 39-3: In a dry, necked flask, substrate 39-2 (7.00 g, 23.90 mmol) and K2CO3 (3.96 g, 28.68 mmol) were added, dissolved in ACN (50 mL), and stirred at room temperature for 1 hour, then monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: product 39-3 (1.41 g, 6.59 mmol), LC-MS (ESI + )m / z:215.1 [M+H]+. Step 3: Synthesis of compound 39-4: Substrate 39-3 (427.9 mg, 2.00 mmol) was added to a dry necked flask, dissolved in ACN (4 mL), and NaBH4 (151.8 mg, 4.00 mmol) was slowly added in an ice bath. The reaction was carried out in an ice water bath for 1 hour and monitored by TLC. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain product 39-4 (210.00 mg, 0.98 mmol). Step 4: Synthesis of compound 39: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 39-4 (42.79 mg, 0.20 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 39 (10.0 mg, 22.56 μmol). 1 1H NMR (600 MHz, Methanol-d6)δ 9.82(s,1H),9.02(s,1H),8.25(s,1H),8.17(s,1H),7.95(d,J=8.4Hz,1H),7.72(d,J=8.4Hz,2H),7.05(d, J=8.4Hz,1H),6.95(d,J=9.0Hz,2H),5.80(d,J=6.0Hz,1H),5.39(q,J=3.2Hz,1H),4.66-4.63(m,1H),4.35 -4.33(m,1H),3.08(s,4H),2.46(s,4H),2.23(s,3H).LCMS(ESI + )m / z:444.2 [M+H] + ,HPLC method B:R T =6.24min, purity:88.2%.

[0076] Example 40: Synthesis of Compound 40 TIFF0007866564000108.tif74170 Step 1: Synthesis of Compound 40-2: The following compound was obtained by following the synthesis method of Step 1 in Example 29, except that 40-1 (423.90 mg, 2.00 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Compound 40-2 (210.00 mg, 0.98 mmol), LCMS (ESI + )m / z:211.2 [M+H-H2O] + . Step 2: Synthesis of compound 40: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 40-2 (45.59 mg, 0.20 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 40 (20.00 mg, 43.74 μmol). 1H NMR(600MHz,Methanol-d4)δ 9.83(s,1H),9.02(s,1H),8.25(s,1H),8.15(s,1H),7.93(d,J=9.6Hz,1H),7.72(d,J=8.4Hz,2H),7.03(d,J=9.0Hz,1H),6.95( d,J=8.4Hz,2H),5.68(s,1H),4.42(d,J=9.6Hz,1H),4.38(d,J=9.6Hz,1H),3.08(s,4H),2.46(s,4H),2.22(s,3H),1.61(s,3H). LCMS(ESI + m / z:458.1 [M+H] + HPLC method B:R T =6.53min, purity: 87.3%. Compound 40 was divided into two parts, and the following results were obtained: Compound 40-A and Compound 40-B. 40-A: 1 H NMR(600MHz,DMSO-d6)δ 9.83(s,1H),9.02(s,1H),8.25(s,1H),8.16(s,1H),7.93(d,J=8.4Hz,1H),7.72(d,J=8.4Hz,2H),7.03(d,J=8.4Hz,1H),6.95( d,J=9.6Hz,2H),5.69(s,1H),4.42(d,J=9.6Hz,1H),4.38(d,J=9.6Hz,1H),3.07(s,4H),2.46(s,4H),2.22(s,3H),1.62(s,3H). LCMS(ESI + m / z:458.1 [M+H] + HPLC: Method B: R T :6.40min, purity:95.5%. 40-B: 1H NMR(600MHz,DMSO-d6)δ 9.83(s,1H),9.02(s,1H),8.25(s,1H),8.15(s,1H),7.93(d,J=8.4Hz,1H),7.72(d,J=8.4Hz,2H),7.03(d,J=8.4Hz,1H),6.95(d,J =9.6Hz,2H),5.69(s,1H),4.43(d,J=9.6Hz,1H),4.38(d,J=9.6Hz,1H),3.08(s,4H),2.50-2.46(m,4H),2.22(s,3H),1.61(s,3H). LCMS(ESI + )m / z:458.1 [M+H] + . HPLC: Method B, R T :6.53min, Purity: 100%.

[0077] Example 41: Synthesis of Compound 41: TIFF0007866564000109.tif35170 Step 1: Synthesis of compound 41-1: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 41-1 (38 mg, 0.194 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 41 (2.0 mg, 4.50 μmol). 1 H NMR(600MHz,DMSO-d6)δ 11.34(s,1H),9.79(s,1H),9.03(s,1H),8.28(d,J=4.8Hz,1H),8.08(s,1H),7.85(dd,J=8.4Hz,1H),7.75-7. 71(m,3H),7.46(t,J=2.4Hz,1H),6.95(d,J=9.0Hz,2H),6.52(s,1H),3.09(s,4H),2.48(s,4H),2.24(s,3H). LCMS(ESI + )m / z:425.1 [M+H] + ,HPLC method B:R T= 7.54min, purity: 95.5%.

[0078] Example 42: Synthesis of Compound 42: TIFF0007866564000110.tif35170 Step 1: Synthesis of compound 42-2: Compound 42-2 (850 mg, crude) was obtained by the same synthesis method as in Step 1 of Example 29, except that 42-1 (1 g, 4.29 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1. TLC (PE / EA = 3 / 1) showed that the starting materials had completed their reaction and new points had been formed. Step 2: Synthesis of compound 42: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 42-2 (63 mg, 0.269 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 42 (12 mg, 23.56 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.85(s,1H),9.03(s,1H),8.40(d,J=4.8Hz,1H),8.29(s,1H),8.06(s,1H),7.73(d,J=7.8Hz,2H),7.37(q ,J=11.4Hz,1H),6.96(d,J=9.0Hz,2H),5.47(s,1H),3.09(s,4H),2.47(s,3H),2.23(s,4H),1.58(s,6H). LCMS(ESI + )m / z:462.1 [M+H] + ,HPLC method B:R T= 7.56min, purity: 93.9%.

[0079] Example 43: Synthesis of Compound 43 TIFF0007866564000111.tif34170 Step 1: Synthesis of compound 43-2: The following compound was obtained by following the synthesis method of Step 1 in Example 29, except that 43-1 (452.00 mg, 2.00 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Compound 43-2 (200 mg, 0.88 mmol), LCMS (ESI + )m / z:209.2 [M+H-H2O] + . Step 2: Synthesis of compound 43: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 43-2 (45.20 mg, 0.20 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 43 (10.00 mg, 21.96 μmol). 1 H NMR(600MHz,Methanol-d6)δ 9.85(s,1H),9.02(s,1H),8.27(s,1H),8.17(s,1H),7.74(d,J=8.4Hz,2H),7.39(d,J=8.4Hz,1H),7.16(d,J=8.4Hz,1H),6.84 (d,J=8.4Hz,2H),5.13(s,1H),3.09(s,4H),2.87-2.79(m,2H),2.49(s,4H),2.26(s,3H),2.04(t,J=7.2Hz,2H),1.47(s,3H). LCMS(ESI + )m / z:456.1 [M+H] + ,HPLC method B:R T =7.17min, purity: 93.5%.

[0080] Example 44: Synthesis of Compound 44 TIFF0007866564000112.tif38170 Step 1: Synthesis of compound 44-2: The following compound was obtained by following the synthesis method of Step 1 in Example 29, except that 44-1 (452.00 mg, 2.00 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Compound 44-2 (200.00 mg, 0.88 mmol), LCMS (ESI + )m / z:209.2 [M+H-H2O] + . Step 2: Synthesis of compound 44: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 44-2 (45.20 mg, 0.20 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 44 (10.0 mg, 21.96 μmol). 1H NMR(600MHz,DMSO-d6)δ 9.75(s,1H),9.02(s,1H),8.27(s,1H),7.62(d,J=8.4Hz,2H),7.57(d,J=8.4Hz,1H),7.45-7.40(m,2H),6.84(d,J=8. 4Hz,2H),5.19(s,1H),3.05(s,4H),2.95-2.84(m,2H),2.47(s,4H),2.23(s,3H),2.06(t,J=7.2Hz,2H),1.46(s,3H). LCMS(ESI + )m / z:456.1 [M+H] + ,HPLC method B:R T =6.50min, purity: 94.0%.

[0081] Example 45: Synthesis of Compound 45 TIFF0007866564000113.tif35170 Step 1: Synthesis of compound 45-2: In a dry, necked flask, substrate 45-1 (1.23 g, 5.00 mmol) and a solution of AcOH (1 mL) in THF (4 mL) were added. Zn powder (3.30 g, 50.00 mmol) was slowly added at room temperature, and the mixture was stirred at room temperature for 0.5 hours, monitored by TLC. After the reaction was complete, the mixture was filtered through diatomaceous earth, the mother liquor was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain product 45-2 (0.86 g, 4.0 mmol). Step 2: Synthesis of compound 45-3 In a dry, necked flask, combine substrate 45-2 (214.0 mg, 1.0 mmol) and CH(OMe) 3( 3 mL was added, stirred at room temperature for 1 hour, and monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure and the following was obtained: Product 45-3 (210.00 mg, 0.95 mmol), LC-MS (ESI + )m / z:225.2 [M+H] + . Step 3: Synthesis of Compound 45 The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 45-3 (44.79 mg, 0.20 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 45 (10.00 mg, 22.06 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.82(s,1H),9.04(s,1H),8.40(s,2H),8.31(s,1H),8.05(d,J=7.8Hz,1H),7.86(s,1H),7.68(d,J=8.4Hz,2H ),6.94(d,J=9.0Hz,2H),4.31(q,J=7.2Hz,2H),3.10(s,4H),2.47(s,4H),2.23(s,3H),1.42(t,J=7.2Hz,3H). LCMS(ESI + )m / z:454.1 [M+H] + ,HPLC method B:R T =6.44min, purity: 96.5%.

[0082] Example 46: Synthesis of Compound 46 TIFF0007866564000114.tif37170 Step 1: Synthesis of Compound 46: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 46-1 (57 mg, 0.269 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 46 (8.8 mg, 19.26 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.83(s,1H),9.05(s,1H),8.78(s,1H),8.68(s,1H),8.42(d,J=8.4Hz,1H),8.34(s,1H),7. 79-7.74(m,3H),7.02(d,J=8.4Hz,2H),4.46(s,2H),3.10(s,4H),2.47(s,4H),2.23(s,3H). LCMS(ESI + )m / z:441.1 [M+H] + ,HPLC method B:R T =7.56min, purity: 96.5%.

[0083] Example 47: Synthesis of Compound 47 TIFF0007866564000115.tif64170 Step 1: Synthesis of compound 47-2: In a dry, necked flask, 47-1 (3 g, 21 mmol) was added, and DCM (60 mL) was added and dissolved. Subsequently, DIPEA (3.27 g, 25 mmol) and N-methylpiperazine (2.1 g, 21 mmol) were added, and the mixture was stirred at room temperature for 1 hour. Water (50 mL) was added to the reaction mixture, and after thorough stirring, the mixture was separated. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was used directly in the next step without purification to obtain the following: Crude product 47-2 (4.2 g, crude), which was a yellow solid. Step 2: Synthesis of compound 47-3: In a dry, necked flask, 47-2 (2.2g, 10 mmol) was added, methanol (100 mL) was added to dissolve it, ammonium chloride (2.6g, 50 mmol) was added, and zinc powder (3.3g, 50 mmol) was slowly added under stirring conditions. Heat dissipation occurred, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered, the filtrate was concentrated, and the residue was purified by column chromatography using a silica gel column (DCM:MeOH = 8:1) to obtain the following product: product 47-3 (1.2g), which was a brown solid. Step 3: Synthesis of compound 47-4: In a dry, necked flask, 47-3 (400 mg, 2.1 mmol) and 1-2 (323 mg, 2.1 mmol) were added, and a mixed solvent of 1,4-dioxane / acetic acid (20 mL / 2 mL) was added to dissolve them. The mixture was heated to 110°C and reacted for 4 hours. After the reaction was complete, the reaction mixture was cooled, the solvent was concentrated, and residual impurities were purified by column chromatography using a silica gel column (DCM:MeOH = 10:1). The following was obtained: 47-4 (260 mg), which was a yellow solid. Step 4: Synthesis of compound 47-6: In a dry two-necked flask, methylmagnesium iodide (2M in THF, 21.5 mL) was added, and under ice bath and nitrogen protection conditions, 47-5 (2 g, 8.7 mmol) in THF (dry, 20 mL) solution was added and the mixture was slowly heated to room temperature and stirred overnight. The reaction was stopped with saturated ammonium chloride solution (50 mL), then extracted three times with ethyl acetate, the organic phase was combined, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography using a silica gel column (PE / EA = 5 / 1) to obtain the following product: 47-6 (1.8 g), which was a clear oily substance. Step 5: Synthesis of compound 47-7: In a dry three-necked flask, 47-6 (430 mg, 2 mmol) was added, dissolved with anhydrous THF (20 mL), protected with nitrogen, cooled to -78°C, then slowly added n-butyllithium (2.5 M, 1.2 mL) dropwise, stirred for 0.5 hours, then added triisopropyl borate (560 mg, 3 mmol), continued stirring for 2 hours, stopped the reaction with water (30 mL), extracted three times with ethyl acetate, combined the organic phase, dried over anhydrous sodium sulfate, filtered, and concentrated the filtrate under reduced pressure to obtain the following: crude product 47-7 (380 mg, crude), a white solid, which was used directly in the next step of the reaction. Step 6: Synthesis of compound 47: In a dry, necked flask, 47-4 (31 mg, 0.1 mmol), 47-7 (27 mg, 0.15 mmol), and pyridine (16 mg, 0.2 mmol) were added, dissolved in DCM, and copper acetate (36 mg, 0.2 mmol) was added. The mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by Prep-TLC and then further purified by Prep-HPLC to obtain compound 47 (3 mg, 6.15 μmol). 1H NMR(600MHz,Methanol-d4)δ 8.94(s,1H),8.59(d,J=2.7Hz,1H),8.32(d,J=1.7Hz,1H),8.17(s,1H),8.04(dd,J=9.1,2.7Hz,1H),7.95(d, J=5.6Hz,1H),7.54-7.45(m,2H),6.92(d,J=9.1Hz,1H),3.61(s,4H),2.87(s,4H),2.57(s,3H),1.58(s,6H). LCMS(ESI + )m / z:445.2 [M+H] + ,HPLC method B:R T =5.12min, purity: 91.1%.

[0084] Example 48: Synthesis of Compound 48 TIFF0007866564000116.tif35170 Step 1: Synthesis of compound 48-3: In a dry, necked flask, substrates 48-1 (399.9 mg, 2.0 mmol), 48-2 (190.08 mg, 2.0 mmol), Cu(OAc)2 (39.93 mg, 0.2 mmol), cesium carbonate (325.82 mg, 1.0 mmol), and N,N-dimethylglycine (206.22 mg, 2.00 mmol) were added in a 1,4-dioxane (4 mL) solution. The mixture was stirred at 100°C for 18 hours and monitored by LC-MS. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, the mother liquor was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: Product 48-3 (250.00 mg, 1.03 mmol), LCMS (ESI + )m / z:250.1 [M+H] + . Step 2: Synthesis of compound 48: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 48-3 (49.79 mg, 0.20 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 48 (12.00 mg, 25.09 μmol). 1H NMR(600MHz,DMSO-d6)δ 9.93(s,1H),9.05(s,1H),8.53(s,1H),8.35(s,1H),8.19(s,1H),7.81(d,J=6.6Hz,1H),7.73-7.71(m,1H),7.62(d,J=8.4Hz,2H),7.60-7 .57(m,1H),7.37(d,J=8.4Hz,1H),6.73(d,J=8.4Hz,2H),6.57(d,J=9.3Hz,1H),6.40-6.37(m,1H),3.02(s,4H),2.48(s,4H),2.24(s,3H). LCMS(ESI + )m / z:479.3 [M+H] + ,HPLC method B:R T =6.35min, purity: 96.9%.

[0085] Example 49: Synthesis of Compound 49 TIFF0007866564000117.tif39170 Step 1: Synthesis of compound 49-3: In a dry, necked flask, substrate 49-2 (2.3 g, 50.0 mmol) and a solution of K2CO3 (11.06 g, 80.0 mmol) in ethanol (60 mL) were added, cooled to 5°C under nitrogen protection, then 49-1 (2.0 g, 10 mmol) was added, and the mixture was stirred at 80°C for 18 hours and monitored by LC-MS. After the reaction was complete, the mixture was cooled to room temperature, concentrated under reduced pressure, extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (PE / EA = 2 / 3) to obtain the following: product 49-3 (1.8 g, 7.96 mmol), LC-MS (ESI + )m / z:226.1 [M+H] + . Step 2: Synthesis of compound 49: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 49-3 (40.69 mg, 0.18 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 49 (1.50 mg, 2.84 μmol). 1H NMR(600MHz,DMSO-d6)δ 9.77(s,1H),9.03(s,1H),8.39-8.33(m,1H),8.27(s,1H),8.02(dd,J=9.0,2.1Hz,1H),7.73(d,J=8.1Hz,2H),7.53 (d,J=9.0Hz,1H),6.94(d,J=8.5Hz,2H),5.55(s,2H),3.80(s,3H),3.07(d,J=5.0Hz,4H),2.46(s,4H),2.23(s,3H). LCMS(ESI + )m / z:455.2 [M+H] + , HPLC method B:R T= 8.92min, purity=86.2%.

[0086] Example 50: Synthesis of Compound 50 TIFF0007866564000118.tif36170 Step 1: Synthesis of Compound 50-2: The following compound was obtained by following the synthesis method of Step 1 in Example 29, except that 50-1 (434.04 mg, 2 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Compound 50-2 (200 mg, 878.09 μmol), which was a white solid. Step 2: Synthesis of compound 50: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 50-2 (37.89 mg, 174.55 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 50 (17 mg, 38.16 μmol). 1 H NMR(600MHz,Chloroform-d)δ 9.44(s,1H),8.89(s,1H),8.70(s,1H),8.17(s,1H),7.57(d,J=8.4Hz,2H),7.43(d,J=7.9Hz,1H ),6.99(d,J=8.9Hz,2H),3.25(t,J=4.9Hz,4H),2.69(t,J=4.8Hz,4H),2.42(s,3H),1.69(s,6H). LCMS(ESI + )m / z:445.2[M+H] + ,HPLC method B:RT = 7.98 min, purity > 87.1%.

[0087] Example 51: Synthesis of Compound 51 TIFF0007866564000119.tif38170 Step 1: Synthesis of Compound 51-2: In a dry, necked flask, substrate 51-1 (600 mg, 3.19 mmol) and triethyl orthoacetate (1.5 mL) were added, the temperature was raised to 100°C, and the reaction was carried out for 12 hours, with the reaction monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure, extracted three times with water and ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. The mixture was then concentrated under reduced pressure to obtain the following: crude product 51-2 (650 mg, crude), which was used directly in the next step of the reaction. Step 2: Synthesis of compound 51: The following compound was obtained by following the same synthesis method as in Step 3 of Example 1, except that 51-2 (65.80 mg, 310.31 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3, and DMF (2 mL) was used instead of 1,4-dioxane (3 mL): Compound 51 (18.1 mg, 36.78 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.86(s,1H),9.07(s,1H),8.39(s,1H),7.87(d,J=7.8Hz,1H),7.76(d,J=7.8Hz,1H),7.59(d,J=8.4Hz, 2H),7.76(t,J=7.8Hz,1H),6.81(d,J=9.0Hz,2H),3.05(s,4H),2.59(s,3H),2.45(s,4H),2.22(s,3H). LCMS(ESI + )m / z:441.2 [M+H] + ,HPLC method B:R T =6.48min, purity: 89.5%.

[0088] Example 52: Synthesis of Compound 52 TIFF0007866564000120.tif35170 Step 1: Synthesis of Compound 52-2: The following compound was obtained by the same synthesis method as in Step 1 of Example 29, except that 52-1 (500.00 mg, 2.15 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Compound 52-2 (300 mg, 1.29 mmol). Step 2: Synthesis of compound 52: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 52-2 (67.81 mg, 290.92 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 52 (4.5 mg, 9.23 μmol). 1 H NMR(600MHz,DMSO-d6)δ 8.79(s,1H),8.04(s,1H),7.73(dd,J=6.6Hz,1H),7.46(d,J=8.4Hz,3H),7.27(s,1H),7.21( d,J=9.0Hz,1H),6.81(d,J=9.0Hz,2H),3.09(s,4H),2.53(s,4H),2.29(s,3H),1.55(s,6H). LCMS(ESI + )m / z:462.2 [M+H] + ,HPLC method B:R T= 6.42 min, purity: 94.7%.

[0089] Example 53: Synthesis of Compound 53 TIFF0007866564000121.tif34170 Step 1: Synthesis of compound 53-2: The following compound was obtained by the same synthesis method as in Step 1 of Example 29, except that 53-1 (1.11 g, 5 mmol) was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1: Compound 53-2 (1.0 g, 4.49 mmol). Step 2: Synthesis of compound 53: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 53-2 (39.80 mg, 180.00 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 53 (7.1 mg, 12.10 μmol). 1H NMR(600MHz,Chloroform-d)δ 8.82(s,1H),8.00(s,1H),7.79(d,J=1.7Hz,1H),7.75(d,J=1.6Hz,1H),7.61-7.56(m,2H),7.31( s,1H),7.01-6.95(m,2H),3.22(t,J=4.9Hz,4H),2.65(t,J=4.8Hz,4H),2.40(s,3H),1.73(s,6H). LCMS(ESI + )m / z:450.2[M+H] + ,HPLC method B:R T = 8.55 min, purity > 76.6%.

[0090] Example 54: Synthesis of Compound 54 TIFF0007866564000122.tif35170 Step 1: Synthesis of compound 54-2: In a dry, necked flask, substrates 54-1 (472 mg, 1.99 mmol), 48-2 (94.74 mg, 996.23 μmol), CuI (37.95 mg, 0.2 mmol), cesium carbonate (323.78 mg, 1.0 mmol), and N,N-dimethylglycine (102.73 mg, 1.0 mmol) were added in a 1,4-dioxane (4 mL) solution. The mixture was stirred at 100°C for 18 hours and monitored by LC-MS. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, the mother liquor was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: product 54-2 (100 mg, 398.28 μmol). Step 2: Synthesis of compound 54: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 54-2 (49.51 mg, 197.18 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 54 (20 mg, 38.12 μmol). 1H NMR(600MHz,DMSO-d6)δ 9.91(s,1H),9.05(s,1H),8.37(s,1H),8.26-8.23(m,1H),8.11(d,J=8.4 Hz,1H),8.02-8.01(m,1H),7.79(d,J=7.8Hz,1H),7.74(d,J=8.4Hz,2H), 7.61-7.58(m,1H),6.68(d,J=8.4Hz,2H),6.61(d,J=9.0Hz,1H),6.35(t, J=6.6Hz,1H),3.01(t,J=4.8Hz,4H),2.47(d,J=5.0Hz,4H),2.24(s,3H). LCMS(ESI + )m / z:480.1[M+H] + , HPLC method B:R T =8.16min, purity >91.4%.

[0091] Example 55: Synthesis of Compound 55 TIFF0007866564000123.tif35170 Step 1: Synthesis of Compound 55-2: Compound 55-2 was obtained by the same synthesis method as in Step 1 of Example 29, except that 55-1 was used instead of 29-1 (500 mg, 2.91 mmol) in Step 1. Step 2: Synthesis of compound 55: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 55-2 (50 mg, 195.99 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 55 (17 mg, 35.16 μmol). 1 H NMR(600MHz,Methanol-d4)δ 9.56(s,1H),8.93(s,1H),8.27(d,J=8.7Hz,1H),8.20(s,1H),7.70(d,J=9.7Hz,1H),7.64-7.39(m, 3H),6.97(d,J=9.0Hz,2H),3.17(t,J=5.1Hz,4H),2.64(t,J=5.0Hz,4H),2.36(s,3H),1.73(s,6H). LCMS(ESI + )m / z:484.2[M+H] +, HPLC method B:R T =5.21min, purity 90.0%.

[0092] Example 56: Synthesis of Compound 56 TIFF0007866564000124.tif68170 Step 1: Synthesis of compound 56-2: In a dry, necked flask, substrate 56-1 (943.17 mg, 5 mmol) and EtOH (10 mL) were added and dissolved with stirring. Then DIPEA (969.30 mg, 7.50 mmol, 1.31 mL) was added, and hydrazine hydrate (272.38 mg, 8.50 mmol) was slowly added dropwise at 0°C. The temperature was raised to 50°C and the reaction was carried out for 1 hour. After the reaction was complete, the reaction mixture was concentrated under reduced pressure to obtain the following: crude product 56-2 (790 mg, 4.75 mmol). Step 2: Synthesis of compound 56-3: The following compound was obtained by following the same synthesis method as in Step 3 of Example 1, except that 30-2 (332.41 mg, 2 mmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3, and 56-2 (330.85 mg, 1.33 mmol) was used instead of 1-3 (105 mg, 339.40 μmol): Compound 56-3 (252 mg, 755.78 μmol). Step 3: Synthesis of compound 56: In a dry, necked flask, substrate 56-3 (66.69 mg, 0.2 mmol), m-CPBA (26.45 mg, 300.00 μmol), and THF (0.8 mL) were added and stirred at room temperature for 10 minutes. Then, DIPEA (129.24 mg, 1.00 mmol) was added and stirred at room temperature for 5 minutes. Finally, substrate 56-4 (57.68 mg, 300.00 μmol) was added and the mixture was reacted at 100°C for 6 hours, monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure, extracted three times with water and ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. The mixture was then concentrated under reduced pressure, and the residue was purified by column chromatography to obtain compound 56 (6.5 mg). 1H NMR(600MHz,DMSO-d6)δ 9.96(s,1H),9.09(s,1H),8.33(s,1H),8.18(d,J=9.1Hz,1H),8.05(d,J=3.1Hz,1H),7.79(dd,J=8.0,2.1Hz,1H),7.76 - 7.75(m,1H),7.47(dd,J=9.1,3.1Hz,1H),7.41 - 7.39(m,1H),6.94(dd,J=8.0,2.1Hz,1H),3.27(s,6H),3.17-3.14(m,4H),2.48(t,J=4.9Hz,4H),2.23(s,3H). LCMS(ESI + )m / z:478.2[M+H] + ,HPLC method B:R T = 5.69 min, purity 89.9%.

[0093] Example 57: Synthesis of Compound 57 TIFF0007866564000125.tif87170 Step 1: Synthesis of compound 57-3: In a dry, necked flask, substrate 57-1 (20 g, 186.65 mmol) and toluene (120 mL) solution were added, followed by substrate 57-2 (15.70 g, 186.65 mmol) and MgSO4 (22.40 g, 186.08 mmol). The mixture was stirred at 30°C for 18 hours and monitored by LC-MS. After the reaction was complete, the mixture was filtered, washed with toluene (40 mL) solution, filtered again, and the following was obtained: product 57-3 (32.34 g, crude). Step 2: Synthesis of compound 57-4: In a dry, necked flask, substrate 57-3 (32.34 g, 186.66 mmol) and toluene (160 mL) solution were added. At 0°C, TEA (19.27 g, 190.40 mmol) was added, and Ac2O (19.44 g, 190.40 mmol) was slowly added dropwise. The mixture was stirred at room temperature for 18 hours and monitored by LC-MS. After the reaction was complete, the solution was washed twice with water, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 57-4 (22.3 g, 103.58 mmol), a yellow oily substance. LC-MS (ESI +)m / z:216.2 [M+H] + . Step 3: Synthesis of compound 57-5: In a dry three-necked flask, substrate 57-4 (22.3 g, 103.58 mmol) was added and dissolved in DMF (75.46 mL). POCl3 (39.71 g, 258.95 mmol) and MgSO4 (22.40 g, 186.08 mmol) were added dropwise under nitrogen protection at -10°C. The mixture was stirred at room temperature for 1 hour, then the temperature was raised to 105°C and the reaction was allowed to proceed for 16 hours, monitored by LC-MS. After the reaction was complete, the mixture was stopped in ice water and the pH was adjusted to 9-10 with 30% sodium hydroxide aqueous solution. The mixture was extracted three times with water and ethyl acetate, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain: Product 57-5 (10.6 g, 69.01 mmol), a yellow solid, LC-MS (ESI + )m / z:154.1 [M+H] + . Step 4: Synthesis of compound 57-6: In a dry, necked flask, substrate 57-5 (3 g, 19.53 mmol) and phthalic anhydride (5.79 g, 39.06 mmol) were added, dissolved in DCM (13.5 mL), and H2O2 (6.64 g, 58.59 mmol) was added. The mixture was stirred at 40°C for 18 hours and monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: product 57-6 (3 g, 17.69 mmol), a white solid, which was analyzed by LC-MS (ESI + )m / z:170.0[M+H] + . Step 5: Synthesis of compound 57-7: In a dry, necked flask, Ac2O (9.03 g, 88.44 mmol) was added, and at 85°C, 57-6 (3 g, 17.69 mmol) in MeCN (20 mL) solution was added dropwise. The mixture was stirred at 85°C for 3 hours and monitored by LC-MS. After the reaction was complete, the mixture was concentrated under reduced pressure, the residue was adjusted to pH 8-9 with saturated sodium bicarbonate solution, extracted three times by DCM, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the following: Product 57-7 (3.8 g, crude), which was a bright yellow oily substance. LC-MS (ESI + )m / z:212.2 [M+H] + . Step 6: Synthesis of Compounds 57-8: In a dry, necked flask, substrate 57-7 (3.74 g, 17.67 mmol), K2CO3 (7.32 g, 53.01 mmol), and MeOH solution (40 mL) were added and stirred at 15°C for 2 hours, and monitored by LC-MS. After the reaction was complete, the mixture was filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: product 57-8 (1.94 g, 11.44 mmol), which was a bright yellow oily substance, LC-MS (ESI + )m / z:170.1 [M+H] + . Step 7: Synthesis of Compound 57-9: In a dry, necked flask, substrate 57-8 (3.74 g, 17.67 mmol) was added, dissolved in DCM (40 mL), and Dess-martin periodinane (7.36 g, 17.36 mmol) was added. The mixture was stirred at 15°C for 2 hours and monitored by LC-MS. After the reaction was complete, the pH was adjusted to 8-9 with saturated sodium bicarbonate solution, extracted three times with DCM, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain product 57-9 (2 g, crude), a white solid, with LC-MS (ESI+) m / z: 168.0 [M+H]+. Step 8: Synthesis of compounds 57-10: In a dry three-necked flask, substrate 57-9 (0.5 g, 2.98 mmol) was added and dissolved in anhydrous THF (15 mL). Methylmagnesium bromide (1 M in THF, 11.93 mL) was slowly added dropwise under ice bath and nitrogen protection, and the mixture was slowly heated to room temperature and stirred for 1 hour. The reaction was stopped with saturated ammonium chloride solution, then extracted three times with EA, the organic phase was combined, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated, and the residue was purified by column chromatography to obtain: product 57-10 (0.29 g, 1.47 mmol), which was yellow and oily, LCMS (ESI+) m / z: 198.0 [M+H]+. Step 9: Synthesis of Compound 57: In a dry, necked flask, substrates 57-10 (16 mg, 80.95 μmol), 1-3 (25 mg, 80.81 μmol), XantPhos (4.67 mg, 8.09 μmol), Pd2(dba)3 (2.59 mg, 2.83 μmol), and t-BuOK (9.08 mg, 80.95 μmol) were added, and 1,4-dioxane (1 mL) was added to dissolve the substances. The mixture was stirred at 150°C for 1 hour under nitrogen protection and monitored by LC-MS. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following product: product 57 (8.33 mg, 17.70 μmol). 1 1H NMR (600MHz, DMSO-d6)δ 9.79(s,1H),8.05(s,1H),8.01(d,J=9.6Hz,1H),7.66(d,J=7.6Hz,1H),7.55 (d,J=8.4Hz,2H),7.34(s,1H),6.89(d,J=9.0Hz,2H),3.23(s,4H),3.00-2.9 6(m,1H),2.95-2.78(s,1H),2.71(s,4H),2.42(s,3H),2.36-2.31(m,1H),2. 22-2.17(m,1H),2.06-2.02(m,1H),1.83-1.79(m,1H),0.94(t,J=7.2Hz,3H). LCMS(ESI + )m / z:471.1 [M+H] + ,HPLC method B:R T=4.90min, purity 99.9%.

[0094] Example 58: Synthesis of Compound 58 TIFF0007866564000126.tif66170 Step 1: Synthesis of compound 58-2: In a dry, necked flask, substrate 58-1 (87 mg, 395.46 μmol) and methylamine (120.00 mg, 3.86 mmol, 1 M tetrahydrofuran solution) were added and reacted at room temperature for 2 hours, monitored by LC-MS. After the reaction was complete, the reaction mixture was concentrated under reduced pressure to obtain crude product 58-2, which was used directly in the next step of the reaction. Step 2: Synthesis of compound 58-3: In a dry, necked flask, substrate 58-2 and THF (1 mL) were added and dissolved with stirring. CH3COOH (1 mL) and zinc powder (500 mg) were then added, and the mixture was reacted at room temperature for 2 hours, monitored by LC-MS. After the reaction was complete, zinc powder and insoluble matter were filtered off using diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain crude product 58-3 (25 mg, crude). Step 3: Synthesis of compound 58-4: Substrate 58-3 (25 mg, crude) and triethyl orthoacetate (1 mL) were added to a dry, necked flask and reacted at room temperature for 2 hours, monitored by LC-MS. After the reaction was complete, the reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain product 58-4 (7 mg, 31.10 μmol). Step 4: Synthesis of compound 58: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 58-4 (34.7 mg, 154.16 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 58 (2.0 mg, 4.41 μmol). 1H NMR(600MHz,DMSO-d6)δ 9.82(s,1H),9.04(s,1H),8.30(d,J=4.1Hz,2H),7.96(dd,J=8.7,2.1Hz,1H),7.72(d,J=8.4Hz,2H),7.69(d,J=8. 6Hz,1H),6.98-6.92(m,2H),3.78(s,3H),3.10(t,J=4.9Hz,4H),2.58(s,3H),2.47(t,J=4.9Hz,4H),2.23(s,3H). LCMS(ESI + )m / z:454.1 [M+H] + ,HPLC method B:R T =6.50min, purity 92.2%.

[0095] Example 59: Synthesis of Compound 59 TIFF0007866564000127.tif35170 Step 1: Synthesis of compound 59-2: In a dry two-necked flask, substrate 59-1 (1 g, 5.32 mmol) and sodium bicarbonate (893.62 mg, 10.64 mmol) were added, dissolved with THF (8 mL), and under nitrogen protection at 0°C, chloroacetyl chloride (600.69 mg, 5.32 mmol) was added and stirred for 30 minutes. Then K2CO3 (1.47 g, 10.64 mmol) was added, and the temperature was raised to 80°C and the reaction was carried out for 3 hours. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the following: crude product 59-2 (1.4 g, crude). Step 2: Synthesis of compound 59-3: In a dry two-necked flask, substrate 59-2 (500 mg, 2.19 mmol) and cesium carbonate (785.82 mg, 2.41 mmol) were added, DMF (2.5 mL) was added, and the mixture was dissolved with stirring. Iodoethane (341.96 mg, 2.19 mmol) was added at 0°C and under nitrogen protection, and the mixture was allowed to return to room temperature and react for 2 hours. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by medium-pressure chromatography to obtain product 59-3 (190 mg, 741.91 μmol). Step 3: Synthesis of compound 59: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 59-3 (34.60 mg, 135.11 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 59 (3.49 mg, 7.07 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.78(s,1H),9.03(s,1H),8.29(s,1H),7.88(d,J=2.4Hz,1H),7.82(dd,J=8.4Hz,1H),7.60(d,J=9.0Hz,2H),),7.23(d,J=3.0Hz,1H) ),6.93(d,J=9.0Hz,2H),4.70(s,2H),3.90(d,J=7.2Hz,2H),3.09(t,J=4.8Hz,4H),2.47(s,4H),2.23(s,3H),1.08(t,J=7.2Hz,3H). LCMS(ESI + )m / z:485.2 [M+H] + ,HPLC method B:R T= 5.67min, purity: 95.1%.

[0096] Example 60: Synthesis of Compound 60 TIFF0007866564000128.tif31170 Step 1: Synthesis of compound 60-2: In a dry two-necked flask, substrate 60-1 (200 mg, 1.30 mmol) and potassium carbonate (540 mg, 3.91 mmol) were added, DMF (2.5 mL) was added, and the mixture was dissolved with stirring. Iodoethane (406.24 mg, 2.60 mmol) was added at 0°C and under nitrogen protection, and the temperature was raised to 75°C and the mixture was reacted for 1 hour. After the reaction was complete, the mixture was extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by medium-pressure chromatography to obtain product 60-2 (140 mg, 770.83 μmol). Step 2: Synthesis of compound 60: The following compound was obtained by the same synthesis method as in Step 2 of Example 28, except that 60-2 (35.22 mg, 193.94 μmol) was used instead of 28-2 (55.13 mg, 269.37 μmol) in Step 2: Compound 60 (4.13 mg, 8.20 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.91(s,1H),9.05(s,1H),8.55(s,1H),8.44(d,J=8.8Hz,1H),8.36(s,1H),7.97(s,2H),7.90(d,J=8.8Hz,1H),6.98(d, J=8.8Hz,2H),4.54(q,J=16.8Hz,2H),3.09(t,J=4.4Hz,4H),2.47(t,J=4.8Hz,4H),2.23(s,3H),1.59(t,J=3.2Hz,3H). LCMS(ESI + )m / z:455.1 [M+H] + ,HPLC method A:R T= 5.86min, purity: 90.3%.

[0097] Example 61: Synthesis of Compound 61 TIFF0007866564000129.tif39170 Step 1: Synthesis of Compound 61-2: In a dry three-necked flask, substrate 61-1 (1 g, 4.72 mmol) and THF (10 mL) solution were added. Cooled under nitrogen protection to -40°C, n-BuLi (2.5 M in THF, 4.15 mL) was slowly added dropwise, and the mixture was stirred at -40°C for 1 hour. Then, 1,2-dibromoethane (2.66 g, 14.15 mmol) was slowly added dropwise, and the mixture was gradually returned to room temperature and stirred for 12 hours, monitored by LC-MS. After the reaction was complete, the mixture was stopped with 4N HCl (5 mL), extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain: product 61-2 (1.2 g, crude), LC-MS (ESI + )m / z:238.1 [M+H] + . Step 2: Synthesis of compound 61-3: In a necked flask, substrate 61-2 (700 mg, 2.94 mmol), iodoethane (458.57 mg, 2.94 mmol), and Cs2CO3 (1.05 g, 3.23 mmol) were added, DMF (3 mL) was added, and the mixture was dissolved with stirring. The reaction was carried out at 75°C for 8 hours and monitored by LC-MS. After the reaction was complete, the mixture was stopped with 4N HCl (5 mL), extracted three times with water and ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the following: product 61-3 (285 mg, 1.07 mmol), LC-MS (ESI + )m / z:266.1 [M+H] + . Step 3: Synthesis of compound 61: The following compound was obtained by the same synthesis method as in Step 3 of Example 1, except that 61-3 (30 mg, 112.73 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3: Compound 61 (8.85 mg, 17.89 μmol). 1 H NMR(400MHz,DMSO-d6)δ 9.82(s,1H),9.03(s,1H),8.30(s,1H),7.89-7.85(m,2H),7.64(d,J=8.8Hz,2H),7.21(d,J=8.4Hz,1H),6.93(d,J=9.2Hz,2H),3.80(q, J=14.0Hz,2H),3.09(t,J=4.8Hz,4H),2.46(t,J=4.8Hz,4H),2.23(s,3H),1.71-1.68(m,2H),1.58-1.57(m,2H),1.13(t,J=7.2Hz,3H). LCMS(ESI + )m / z:495.3 [M+H]+, HPLC method A:R T =6.17min, purity 99.9%.

[0098] Example 62: Synthesis of Compound 62 TIFF0007866564000130.tif81170 Step 1: Synthesis of compound 62-2: In a dry, necked flask, substrate 62-1 (192 mg, 997.71 μmol) and hydrazine hydrate solution (160 mg, 4.99 mmol) were added, ethanol (3 mL) was added, and the mixture was dissolved with stirring. The temperature was raised to 80°C and the reaction was carried out for 16 hours, monitored by LC-MS. After the reaction was complete, the reaction mixture was concentrated under reduced pressure, and the residue was purified by medium-pressure chromatography to obtain product 62-2 (180 mg, 957.32 μmol). Step 2: Synthesis of compound 62-4: In a dry microwave tube, substrates 62-2 (142 mg, 755.2 μmol), 62-3 (77.1 mg, 755.2 μmol), and methanol (2 mL) were added and reacted in an oil bath at 60°C for 1 hour under nitrogen protection. After the reaction was complete, the reaction mixture was concentrated under reduced pressure, and then 1,4-dioxane (2 mL) and iodobenzene acetate (267.2 mg, 830.7 μmol) were added and reacted overnight under nitrogen protection and room temperature conditions, monitored by LC-MS. After the reaction was complete, the reaction mixture was concentrated under reduced pressure, extracted three times with ethyl acetate and water, the organic phase was washed three times with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the following: crude product 62-4 (116 mg, 429.5 μmol), which was an orange solid. Step 3: Synthesis of Compound 62: In the same synthesis method as in Step 3 of Example 1, except that 62-4 (134 mg, 496.14 μmol) was used instead of 1-5 (109.92 mg, 441.22 μmol) in Step 3, a carboxylation group removal reaction occurred during the reaction, resulting in the acquisition of compound 62 (10 mg, 19.06 μmol). 1 H NMR(600MHz,DMSO-d6)δ 9.94(s,1H),9.36(d,J=18.3Hz,2H),9.06(s,1H),8.38(s,1H),8.32(dd,J=9.8,2.0Hz,1H),8.07(d,J=9.9Hz,1H),7.6 6(d,J=8.6Hz,2H),7.00(d,J=8.7Hz,2H),3.17(d,J=5.3Hz,1H),3.12(t,J=5.0Hz,4H),2.49-2.47(m,4H),2.23(s,3H). LCMS(ESI+ )m / z:427.2 [M+H]+, HPLC method B:R T =5.48min, purity: 97%.

[0099] Biological activity evaluation measurement: Unless otherwise specified, compound AZD-1775 is used as a control in some of the biological evaluation experiments of this embodiment, and the structural information of AZD-1775 (CAS number 955365-80-7) is as follows: TIFF0007866564000131.tif60170

[0100] Test Example 1: Evaluation of compounds in the binding of Wee1 protein to Tracer 178 using the TR-FRET method. First, compound solutions with different concentration gradients were prepared. The compounds were dissolved in DMSO, and while adding DMSO as a positive control (maximum signal control) and a negative control (minimum signal control), the compounds were diluted fourfold so that the final level of DMSO in each reaction well reached 0.25%. Two parallel replicas were set up for each concentration, resulting in a total of 10 dose points. The compounds were prepared at different concentrations in buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% Brij-35) WEE1 (Thermo Fisher, Cat# PR7373A) protein final reaction concentration 15 nM). The reaction substrates Tracer 178 (Invitrogen, PV5593) and MAb Anti-GST-Eu crypate (Cisbio, 61GSTKLA) were added to a 384-well plate (Corning, cat#3574), centrifuged at 1000 rpm for 1 minute, and incubated on a shaker at 25°C for 60 minutes at 300 rpm. Tracer 178 and MAb Anti-GST-Eu crypate were prepared in buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% Brij-35), with final reaction concentrations of 50 nM for Tracer 178 and 2 nM for MAb Anti-GST-Eu crypate. A negative control (minimum signal control) was used instead of the protein solution using the same amount of buffer. After incubation was complete, fluorescence signal values ​​were read using a BMG PHERAStar reader (using 337 nm as excitation light and 620 nm and 665 nm as emission light). The fluorescence signal ratio was calculated: 665 / 620 * 1000 was the final enzyme activity signal value. The TR-FRET signal was normalized against readings obtained from positive control (maximum signal control) and negative control (minimum signal control) to give the inhibition rate at different concentrations of the compound. The IC50 of enzyme activity inhibition was calculated using GraphPad Prism 6 by fitting a log(inhibitor) vs. response-variable gradient model. The fitting formula is as follows: Y = Bottom + (Top - Bottom) / (1 + 10^((LogIC50 - X) * HillSlope)), where Y represents the known percentage residual enzyme activity and X represents the known concentration of the compound after log. The Wee1 inhibitory activity of the example compounds was measured according to the method described above, and the test results are shown in Table 1. The IC of each compound 50 When we sought and classified them according to the description, the results were as follows: "-":I C 50 Measurement value exceeds 10 μM. "+": IC 50 Measured values ​​less than 10 μM and greater than 1 μM. "++": IC 50 Measured values ​​less than 1 μM and greater than 100 nM. "+++": IC 50 Measured values ​​below 100 nM and above 10 nM, "++++": IC 50 Measured values ​​below 10 nM and above 1 nM, "+++++": IC 50 Measured value: 1 nM or less.

[0101] [Table 1] As can be seen from the above experiments, the compounds disclosed in this invention have significant inhibitory activity against Wee1 kinase.

[0102] Test Example 2: Evaluation of the antiproliferative effect of compounds on H1299 cells and MIA Paca-2 cells using the Cell Titer-Glo method. Compound solutions with different concentration gradients were prepared. The test compound at a concentration of 10 mM and the reference compound AZD1775 at a concentration of 10 mM were dissolved in DMSO. The compounds were then serially diluted with culture medium, and two parallel replicates were set up for each concentration, resulting in a total of nine dose points. The cell proliferation group without the compound was used as the positive control (maximum signal control), and the culture medium was used as the negative control (minimum signal control). The process was carried out while ensuring that the final concentration of DMSO in each reaction well was 0.2%. After removing the culture medium from the 384-well plate, 25 µl of the prepared compounds at different concentrations were transferred to the well plate, and the compounds and cells were cultured for 3 days in a cell incubator at 37°C and 5% CO2. The 384-well plate was removed from the cell incubator and equilibrated at room temperature for 1 hour. Then, 25 µl of Cell Titer-Glo assay reagent was added to each well, dissolved on a shaker for 2 minutes, and after 10 minutes of incubation, the luminescence was read using a BMG PHERAStar. The inhibition rate was calculated from the luminescence signal: first, the mean of the positive control (maximum signal control) and negative control (minimum signal control) was calculated. The inhibition rates of cells at different concentrations of a compound were calculated using TIFF0007866564000133.tif33170. IC50 was calculated by fitting a log(inhibitor) vs. response-variable gradient model to GraphPad Prism 6. The fitted equation is as follows: Y = Bottom + (Top - Bottom) / (1 + 10^((LogIC50 - X) * HillSlope)), where Y is the inhibition rate and X is the concentration of the known compound after logging. Table 2 shows the results of in vitro anti-cell proliferation assays of the example compounds H1299 and MIA Paca-2 using the method described above, and the IC of each compound. 50 We determined and classified them according to the following description: "-":I C 50 Measurement value exceeds 50 μM. "+": IC 50 Measured values ​​below 50 μM and above 20 μM, "++": IC 50 Measured values ​​below 20 μM and above 5 μM, "+++": IC 50 Measured values ​​below 5 μM and above 1 μM, "++++": IC 50 Measured values ​​below 1 μM and above 0.1 μM, "+++++": IC 50 Measured value: 0.1 μM or less.

[0103] [Table 2] Conclusion: The compounds of the present invention have relatively strong cell proliferation inhibitory activity against H1299 and MIA Paca-2.

[0104] Test Example 3: In vitro evaluation of metabolic stability of liver microsomes (mouse and human). 1. Preparation of the working solution Microsomes were removed from a -80°C refrigerator, rapidly thawed in a 37°C water bath, and placed on ice before use. A 10 mM stock solution was prepared by diluting the test sample with DMSO, and then diluted with acetonitrile to prepare a 0.5 mM secondary stock solution. Microsomes were diluted to 0.75 mg / ml using Buffer C. Next, based on n=2 and 5 time points, the secondary stock solution was prepared by adding a compound at a final concentration of 1.5 μM as a working solution, and 350 μL of each compound was prepared and placed on ice before use. NADPH was diluted with Buffer C to prepare a 6 mM working solution as a starter solution. An acetonitrile solution containing an internal standard was prepared as a precipitating agent, and Verapamil-HCl was selected as the internal standard at a concentration of 4 ng / ml. 2. Experimental procedure: Using a round-bottom well plate designated as the reaction plate, 30 μL / well of the prepared working solution for each compound was dispensed into the well plate according to the number of replications and time point (0-hour samples were also added to the reaction plate), and the plate was incubated at 37°C for 10 minutes. In another plate with pointed-bottom wells designated as the precipitation plate, 135 μL of precipitant was added per well. After 10 minutes of incubation, the 0-hour samples were transferred to the plate, and 15 μL of starter solution was added. The precipitation plate was placed on ice before centrifugation. A sufficient amount of diluted starter solution was added to the dispensing plate to facilitate the plate gun aspiration operation. The reaction was carried out on a warm incubation shaker, and 15 μL of starter solution / sample was added to the plate using a volumetric lance. The reaction started with a gentle shake, and the time was accurately measured and recorded using a timer. After the reaction time had elapsed, the solution in the plate was aspirated using a displacement gun and added to the precipitation plate, at which point the reaction was terminated. After all reactions were complete, the plate was shaken for 10 minutes in a 600 rpm plate shaker to precipitate the protein. The mixture was centrifuged at 4°C at maximum speed for 15 minutes, 80 μL of the supernatant was taken, mixed with 320 μL of pure water, and subjected to LC-MS analysis.

[0105] 3.Measurement results: [Table 3] Conclusion: The compounds of the present invention exhibit good in vitro metabolic stability in liver microsomes (mouse and human).

[0106] Test Example 4: Evaluation of Plasma Protein Binding Rate (PPB) 1. Experimental Procedure Sample preparation: The compound was dissolved in DMSO to prepare a 10 mM stock solution. Next, the compound was diluted with PBS to prepare a 0.02 mM secondary stock solution. This 0.02 mM solution was then diluted to 1 μM using blank plasma and prepared as the sample for incubation. Preparation of the dialysis setup: First, 400 μL of blank PBS was added to the white wells of the equilibrated dialysis plate, 200 μL of the prepared plasma sample was added to the red wells, and the dialysis plate was sealed with sealing film. Preparation of recovery plates: Two 96-well deep-well plates labeled T0 and T5 were prepared. All plasma samples were added in a ratio of n=2. 300 μL of acetonitrile (Verapamil-HCl, 4 ng / mL) was added directly to the T0 plate, followed by 50 μL of blank PBS. The mixture was mixed for 5 minutes and incubated in a 4°C refrigerator until incubation was complete. Experimental procedure: The dialysis machine and T5 plate were incubated together in a microplate incubator (37°C, 300 rpm or minimum rotation speed) for 5 hours. At the end of incubation, 300 μL of acetonitrile (Verapamil-HCl, 4 ng / mL) was added, followed by 50 μL of PBS solution. After the dialysis incubation was complete, a new 96-well deep-well plate was prepared. 50 μL of plasma wells were added to the corresponding positions on the 96-well plate, followed by 300 μL of acetonitrile and 50 μL of blank PBS. 50 μL of buffer wells were added to the corresponding positions on the 96-well plate, followed by 300 μL of acetonitrile and 50 μL of blank plasma. 300 μL of acetonitrile (Verapamil-HCl, 4 ng / mL) was added to the plasma-containing wells of the T5 plate, followed by 50 μL of PBS solution. The mixture was shaken for 5 minutes to completely precipitate the protein, and then centrifuged at 20,000 g for 10 minutes at 4°C. 200 μL of the supernatant was added to 200 μL of pure water, mixed thoroughly, and LC-MS / MS analysis was performed. 2. Data Processing and Parameter Calculation Plasma protein binding rate = [(Rpe - Rb) / Rpe] × 100% Recovery rate = [(Rpe + Rb) / R5h] × 100% Stability=(R5 / R0)×100% Among them: R pe = Ratio of plasma sample peak area to internal standard R b = Ratio of buffer solution peak area of ​​test sample to internal standard R5 = Ratio of incubator-stable sample peak area to internal standard R0 = Ratio of the refrigerator-stable sample peak area to the internal standard

[0107] 3.Measurement results: TIFF0007866564000136.tif62170 Conclusion: The compounds of the present invention have a good ratio of plasma protein binding to free drug. Compared with AZD-1775, the plasma protein binding of the compounds of the present invention was found to be similar and to have less inter-species variability.

[0108] Test Example 5: Membrane Permeability Test (Caco-2) Caco-2 cells were purchased from the American Model Tissue Cell Collection (Rockville, MD). The cell medium was modified Eagle Medium (MEM) containing 10% inactivated fetal bovine serum and 1% non-essential amino acids. Cells were inoculated onto polycarbonate filter membranes (product number 3396) and incubated at 37°C in a 5% CO2 incubator. Cells were cultured for 21-28 days after inoculation, and transport experiments were performed. The density of the cell monolayer was characterized and verified using the apparent permeability (Papp) of Lucifer Yellow. A 10 mM stock solution was prepared by dissolving the compound in DMSO, and this was diluted with Hanks Balanced Salt Solution (HBSS, Invitrogen, Cat# 14025-092) containing 25 mM HEPES (pH 7.4) to prepare the working solution. A 10 μM working solution of the test compound was added to the apical and basolateral sides of Caco-2 cells and incubated at 37°C for 90 minutes. After incubation, the apical and basolateral samples were diluted, and the concentrations of the compound on the apical and basolateral sides were detected by LC-MS / MS. The compound concentrations were quantified using standard curves. Measurement results: [Table 5] Conclusion: The compounds of the present invention have good membrane permeability.

[0109] Test Example 6: Evaluation of the metabolic dynamics of a compound To investigate the pharmacokinetic properties of the compound in mice, six male ICR mice were orally administered an appropriate dose (10 mg / kg) of the compound. The mice were divided into two groups, A and B. Anticoagulated whole blood was collected from group A at 5 minutes, 30 minutes, 2 hours, and 8 hours after administration, and from group B at 15 minutes, 1 hour, 4 hours, and 24 hours after administration, and the plasma was separated. Plasma concentrations of the compounds were measured by LC-MS using a standard curve calibration method. Plasma concentration-time data were fitted to pharmacokinetic parameters using Winnolin 5.2 software. Measurement results: [Table 6] Conclusion: The compounds of the present invention possess good pharmacokinetic properties, clearly improving the half-life of the compounds and reducing their clearance.

[0110] Test Example 7: Solubility Measurement The compound was placed in a buffer solution and shaken at constant temperature for 24 hours. The supernatant was prepared as a solution of approximately 100 μg / ml of the test substance, and its solubility was calculated by reverse-phase high-performance liquid chromatography by gradient elution and by an external standard method. Chromatography conditions: C18 column, mobile phase A: 0.02 M potassium dihydrogen phosphate:acetonitrile = 90:10, mobile phase B:acetonitrile, V: 1.0 ml / min, T: 35°C, λ: 210 nm. Measurement results: [Table 7] Conclusion: The solubility of the compound of the present invention is clearly superior to that of AZD-1775.

[0111] Test Example 8: Evaluation of the inhibitory effect of compounds on cytochrome P450 Enzyme experiments were conducted to quantify the inhibition of CYP450 enzyme activity of each isoform by small molecule inhibitors using fluorescence generated by substrate oxidation with cytochrome P450. The experiments were performed using a 384-well plate (Corning, Cat# 3575) with a reaction buffer of 142.86 mM potassium phosphate, pH 7.4. The solution A components used in the experiments were 26.13 mM NADP+ (Sigma-aldrich, Cat# N0505), 65.77 mM G6P (J&K, Cat# 968161), and 65.42 mM MgCl2 (Sigma-aldrich, Cat# M2670). The solution B component used in the experiments was 40 U / mL G6PDH (Sigma-aldrich, Cat# G6378). The substrate mixtures were 0.05X solution A, 0.01X solution B, 50 mM potassium phosphate, 0.01 mM BOMCC / 0.01 mM EOMCC / 0.001 mM DBOMF. For CYP3A4 and CYP2C9, the reaction system consisted of 50 μL or 20 μL, respectively, containing 3 nM CYP3A4 or 120 nM CYP2C9, a BOMCC substrate mixture, and different concentrations of the test compound. For CYP2C19, CYP2D6, and CYP1A2, the reaction system consisted of 20 μL, containing 12.5 nM CYP2C19, 80 nM CYP2D6 or 1 nM CYP1A2, an EOMCC substrate mixture, and different concentrations of the test compound. The CYP2C8 reaction system consisted of 50 μL of 1.5 nM CYP2C8, a DBOMF substrate mixture, and different concentrations of the test compound. After pre-incubation with the enzyme for 10 minutes, the substrate was added, and the fluorescence signal was read using a BMG PHERAStar at different wavelengths (BOMCC / EOMCC Ex430nm / Em480nm, DBOMF Ex490nm / Em520nm) depending on the substrate. The reaction interval was 30 seconds or longer (set according to the actual number of wells), and the reaction time was 30 minutes. The data were analyzed and processed using GraphPad Prism 6 software to obtain IC50 values.

[0112] Measurement results: [Table 8] Conclusion: None of the compounds of the present invention exhibit any clear CYP inhibitory activity.

[0113] Test Example 9: hERG potassium channel inhibition test Experimental Procedure (1) Experimental materials: Culture of cell lines stably transfected with A.CHO (Chinese hamster ovary cells) The cell line used in the membrane clamp assay was a 10th generation CHO cell line overexpressing hERG potassium channel cDNA. CHO hERG cells were cultured in petri dishes or flasks at 37°C in a 5% CO2 incubator. Cells were dropped onto circular slides 24–48 hours before electrophysiological experiments, cultured in cell medium, and used for experiments after the cells had adhered. The cell culture medium (purchased from Invitrogen) consists of the following: - Hams F12 medium -10%(v / v) heat inactivated FBS -100 μg / ml Hygromycin B (thaumatin) -100 μg / ml Geneticin (Genomycin, G418) B. Preparation of Compounds The compound powder was dissolved in an extracellular solution, and sonication and shaking for 5-10 minutes were generally performed to ensure complete dissolution of the compound. The final concentrations of the compounds used in the electrophysiological assay were 5 μM and 20 μM, and DMSO was 0.1%. (2) Experimental Protocol A. Experimental Procedure for Electrophysiological Recording Cell membrane currents were recorded using a HEKA EPC-10 USB membrane clamp amplifier (HEKA Elektronik, Germany). 1) Coverslips with numerous uniformly grown CHO hERG cells on the surface were collected, placed in a continuous recording cell on an inverted microscope, perfused with extracellular fluid (approximately 1 ml per minute), and continuous recording was performed after waiting for the current to stabilize. 2) Using a standard whole-cell recording mode, HERG channel currents were recorded for individual cells. First, the membrane voltage was clamped to -80mV, and the cells were stimulated with +20mV for 5 seconds to activate the hERG potassium channels. Then, they were repolarized to -50mV for 5 seconds to generate an outward tail current, and the cells were continuously perfused until the current stabilized. At that point, the peak value of the tail current was used as the control current value. 3) Next, the extracellular solution containing the test drug was perfused, and the inhibitory effect of the drug on the hERG current was recorded until a steady state was reached. At that point, the peak value of the tail current was taken as the current value after drug administration. 4) Perfuse the cells again with extracellular fluid until the hERG current returns to or approaches the level before drug addition, and then continue perfusing to test other concentrations or drugs. One or more concentrations of compounds or drugs can be tested in each cell. 5) Cisapride (C4740-10mg, Sigma) was used as a positive control in the experiment to confirm that the cells used responded appropriately. (3) Quality control The reported experimental data must meet the following criteria: Electrophysiological recording parameters a) Sealing resistance>500MΩ b) Contact resistance (Ra)<10MΩ c) Initial tail current amplitude > 200 pA d) Current rundown (natural decrease) <2% / min e) Leakage current < 200 pA or 10% of peak hERG current (within 90% of recording time)

[0114] Measurement results: [Table 9] Conclusion: The hERG inhibitory activity of the compound of the present invention is clearly lower than that of AZD-1775.

Claims

1. A compound represented by formula 1, its deuterium compound, its stereoisomer, or a pharmacoposifiable salt thereof. [Here, R １ is selected from the group consisting of hydrogen, halogen, cyano group, -C １～６ alkyl group, -C ２～６ alkenyl group, -C ２～６ alkynyl group, halogen-substituted -C １～６ alkyl group, halogen-substituted -C ２～６ alkenyl group, halogen-substituted -C ２～６ alkynyl group, -C ０～４ alkylene group -OR １１ , -C ０～４ alkylene group -NR １２ R １２ and is selected from the group consisting of R １１ However, -C １～６ Alkyl alkyl group, -C ２～６ Alkenyl group, -C ２～６ Alkynyl group, halogen-substituted -C １～６ Alkyl and halogen-substituted -C ２～６ Alkenyl group, halogen-substituted -C ２～６ Selected from the group consisting of alkynyl groups, Each R １２ However, each independently, hydrogen and -C １～６ Alkyl alkyl group, -C ２～６ Alkenyl group, -C ２～６ Alkynyl group, halogen-substituted -C １～６ Alkyl and halogen-substituted -C ２～６ Alkenyl group, halogen-substituted -C ２～６ Selected from the group consisting of alkynyl groups, The C ring is selected from the group consisting of formula 10. R2 is selected from the group consisting of equation 11, R21 and R22 are each independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, halogen-substituted -C1-6 alkyl group, and -OR24. Each R24 is independently selected from the group consisting of hydrogen and -C1-C6 alkyl groups. R23 and R3, together with the atoms they are linked to, form a 4-membered carbocyclyl group, a 5-membered carbocyclyl group, a 6-membered carbocyclyl group, a 7-membered carbocyclyl group, a 5-membered heterocycloalkyl group, and a 6-membered heterocycloalkyl group. R ５ However, hydrogen, -C １～６ Selected from the group consisting of alkyl groups, Ring A is selected from the group consisting of equation 5, However, it represents a single bond or a double bond. Y １ , Y ２ , Y ３ , Y ４ However, N and CR are independent of each other. Ｙ Selected from the group consisting of, Each R Ｙ However, each is independent of hydrogen, halogen, cyano group, and -C. １～６ Alkyl alkyl group, -C ２～６ Alkenyl group, -C ２～６ Alkynyl group, halogen-substituted -C １～６ Alkyl and halogen-substituted -C ２～６ Alkenyl group, halogen-substituted -C ２～６ Alkynyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, The B ring is selected from the group consisting of a 3-12 membered carbocyclyl group and a 4-12 membered heterocycloalkyl group, and the carbocyclyl group and heterocycloalkyl group are further divided into one, two, three, four or five R groups. Ｂ It may be replaced with, Each R Ｂ is, independently of one another, hydrogen, halogen, cyano group, -C １～６ alkyl group, -C ２～６ alkenyl group, -C ２～６ alkynyl group, halogen-substituted -C １～６ alkyl group, halogen-substituted -C ２～６ alkenyl group, halogen-substituted -C ２～６ alkynyl group, -C ０～４ alkylene group -OR Ｂ１ , -C ０～４ alkylene group -OC(O)R Ｂ１ , -C ０～４ alkylene group -SR Ｂ１ , -C ０～４ alkylene group -S(O) ２ R Ｂ１ , -C ０～４ alkylene group -S(O)R Ｂ１ , -C ０～４ alkylene group -S(O) ２ NR Ｂ１ R Ｂ１ , -C ０～４ alkylene group -S(O)NR Ｂ１ R Ｂ１ , -C ０～４ alkylene group -C(O)R Ｂ１ , -C ０～４ alkylene group -C(O)OR Ｂ１ , -C ０～４ alkylene group -C(O)NR Ｂ１ R Ｂ１ , -C ０～４ alkylene group -NR Ｂ１ R Ｂ１ , -C ０～４ alkylene group -NR Ｂ１ C(O)R Ｂ１ is selected from the group consisting of a 3- to 12-membered carbocyclic group and a 4- to 12-membered heterocycloalkyl group, and the carbocyclic group and the heterocycloalkyl group may be further substituted with one, two, three, four or five R Ｂ１ , or two independent R Ｂ together with the atoms to which they are attached form a group of formula 6, Each R Ｂ１ is, independently of one another, hydrogen, -C １～６ alkyl group, -C ２～６ alkenyl group, -C ２～６ alkynyl group, halogen-substituted -C １～６ alkyl group, halogen-substituted -C ２～６ alkenyl group, halogen-substituted -C ２～６ alkynyl group, and is selected from the group consisting of R ６ , R ７ , R ８ , R ９ However, each is independent of hydrogen, halogen, cyano group, and -C. １～６ Alkyl alkyl group, -C ２～６ Alkenyl group, -C ２～６ Alkynyl group, halogen-substituted -C １～６ Alkyl and halogen-substituted -C ２～６ Alkenyl group, halogen-substituted -C ２～６ Alkynyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, Alternatively, R ６ , R ７ However, together with the atoms linked to them, they form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or R ８ , R ９ However, together with the atoms that link to them, they form a 3-8 membered carbocyacrylic group and a 4-8 membered heterocycloalkyl group. Y ５ , Y ６ However, each is independent of the chemical bond, -C ０～４ Alkylene groups -O-, -C ０～４ Alkylene groups -S-, -C ０～４ Alkylene group - NR Ｙ５１ -, CR Ｙ５１ R Ｙ５１ Selected from the group consisting of, Each R Ｙ５１ However, each independently, hydrogen and -C １～６ Alkyl alkyl group, -C ２～６ Alkenyl group, -C ２～６ Alkynyl group, halogen-substituted -C １～６ Alkyl and halogen-substituted -C ２～６ Alkenyl group, halogen-substituted -C ２～６ Alkynyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, Y ７ However, O, S, NR Ｙ７１ Selected from the group consisting of, R Ｙ７１ However, hydrogen, -C １～６ Alkyl alkyl group, -C ２～６ Alkenyl group, -C ２～６ Alkynyl group, halogen-substituted -C １～６ Alkyl and halogen-substituted -C ２～６ Alkenyl group, halogen-substituted -C ２～６ Alkynyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, R １０ However, hydrogen, halogen, cyano group, -C １～６ Alkyl alkyl group, -C ２～６ Alkenyl group, -C ２～６ Alkynyl group, halogen-substituted -C １～６ Alkyl and halogen-substituted -C ２～６ Alkenyl group, halogen-substituted -C ２～６ Alkynyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups.

2. The C ring is selected from the group consisting of formula 12. The compound according to claim 1, characterized in that m is selected from the group consisting of 0, 1, 2, and 3.

3. A compound represented by formula 1, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Here, R1 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR11, -C0-4 alkylene group -NR12, R12] R 11 is selected from the group consisting of -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Each R12 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. The C ring is selected from the group consisting of equation 7, R2 is selected from the group consisting of equation 13, R21 and R22 are each independently selected from the group consisting of hydrogen and -C1-6 alkyl groups. R5 is selected from the group consisting of hydrogen and -C1-C6 alkyl groups. Ring A is selected from the group consisting of equation 5, However, it represents a single bond or a double bond. Y1, Y2, Y3, and Y4 are each independently selected from the group consisting of N and CRY. Each R Y is independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group), The B ring is selected from the group consisting of a 3- to 12-membered carbocyclyl group and a 4- to 12-membered heterocycloalkyl group, and the carbocyclyl group and heterocycloalkyl group may be further substituted with one, two, three, four, or five R B groups. Each R B independently consists of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR B1, -C0-4 alkylene group -OC(O)R B1, -C0-4 alkylene group -SR B1, -C0-4 alkylene group -S(O)2 R B1, -C0-4 alkylene group -S(O)R B1, -C0-4 alkylene group -S(O)2 NR B1 R B1, -C0-4 alkylene group -S(O)NR B1 R B1, -C 0-4 alkylene group -C(O)R B1, -C 0-4 alkylene group -C(O)OR B1, -C 0-4 alkylene group -C(O)NR B1R B1, -C 0-4 alkylene group -NR B1R B1, -C 0-4 alkylene group -NR B1C(O)R B1, selected from the group consisting of a 3-12 membered carbocyclyl group and a 4-12 membered heterocycloalkyl group, wherein the carbocyclyl group and heterocycloalkyl group may be further substituted with one, two, three, four or five R B1s, or two independent R Bs together with atoms linked to them form the group of formula 6. Each R B1 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. R6, R7, R8, and R9 are each independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group). Alternatively, R6 and R7, together with the atoms they link to, form a 3-8 membered carbocyclyl group or a 4-8 membered heterocycloalkyl group, or R8 and R9, together with the atoms they link to, form a 3-8 membered carbocyclyl group or a 4-8 membered heterocycloalkyl group. Y5 and Y6 are each independently selected from the group consisting of chemical bonds, -C0-4 alkylene group-O-, -C0-4 alkylene group-S-, -C0-4 alkylene group-NR Y51-, and CR Y51 R Y51. Each R Y51 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, halogen-substituted -C2-6 alkynyl groups, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group). Y7 is selected from the group consisting of O, S, NR, and Y71. R Y71 is selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, halogen-substituted -C2-6 alkynyl groups, -C0-4 alkylene groups -OH, -C0-4 alkylene groups -O (C1-6 alkyl groups), -C0-4 alkylene groups -NH2, -C0-4 alkylene groups -NH (C1-6 alkyl groups), and -C0-4 alkylene groups -N (C1-6 alkyl groups) (C1-6 alkyl groups). R 10 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group).

4. A compound represented by formula 1, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Here, R1 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR11, -C0-4 alkylene group -NR12, R12] R 11 is selected from the group consisting of -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Each R12 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. The C ring is selected from the group consisting of equation 2, X1, X2, and X4 are each independently selected from the group consisting of N and CR4. X 3 is selected from the group consisting of N and CR 3. X 5 is selected from the group consisting of O, S, and NR 4. X 6 is selected from the group consisting of CR 4 and N. X 8 is selected from the group consisting of CR 4 R 4 and O. X 7 is selected from the group consisting of S and NR 4. X 9 is selected from the group consisting of CR 4 R 4, R2 is selected from the group consisting of equation 3, R21 and R22 are each independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR24, -C0-4 alkylene group -NR24, R24. Each R 24 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R21 and R22, together with the atoms they are linked to, form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or a group of formula 4. R 23 is hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -C(O)R 25, -C0-4 alkylene group -C(O)NR 25 R 25, -C0-4 alkylene group -C(O)OR 25, -C0-4 alkylene group -S(O)2 R 25, -C0-4 alkylene group -S(O)R 25, -C0-4 alkylene group -S(O)(NH)R 25, -C0-4 alkylene group -S(O)2 NR 25 R 25, -C 0-4 alkylene group -S(O)NR 25 R 25, -C 0-4 alkylene group -S(O)(NH)NR 25 R 25, -C 0-4 alkylene group -OR 25, -C 0-4 alkylene group -OC(O)R 25, -C 0-4 alkylene group -OS(O) 2 R 25, -C 0-4 alkylene group -OS(O)R 25, -C 0-4 alkylene group -NR 25 R 25, -C 0-4 alkylene group -NR 25 C(O)R 25, -C 0-4 alkylene group -NR 25 S(O) 2 R 25, -C 0-4 Selected from the group consisting of alkylene group -NR 25 S(O)R 25, -C 0 to 4, and alkylene group -NR 25 S(O)(NH)R 25. Each R 25 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R23 and R3, together with the atoms they are linked to, form a 4-8 membered carbocyclyl group and a 4-8 membered heterocycloalkyl group, respectively. R3 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, hydroxy-substituted -C1-6 alkyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group), Each R4 is independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group). R5 is selected from the group consisting of hydrogen and -C1-C6 alkyl groups. Ring A is selected from the group consisting of Equation 18, Y １ , Y ２ , Y ３ , Y ４ However, N and CR are independent of each other. Ｙ Selected from the group consisting of, Each R Ｙ However, each is independent of hydrogen, halogen, cyano group, and -C. １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, R ６ , R ７ , R ８ , R ９ However, each independently, hydrogen and -C １～６ Selected from the group consisting of alkyl groups, Alternatively, R ６ , R ７ However, together with the atoms linked to them, they form a 3-membered carbocyacrylic group, a 4-membered carbocyacrylic group, a 5-membered carbocyacrylic group, a 6-membered carbocyacrylic group, a 4-membered heterocycloalkyl group, a 5-membered heterocycloalkyl group, or a 6-membered heterocycloalkyl group. ８ , R ９ However, together with the atoms that link to them, they form a 3-membered carbocyacrylic group, a 4-membered carbocyacrylic group, a 5-membered carbocyacrylic group, a 6-membered carbocyacrylic group, a 4-membered heterocycloalkyl group, a 5-membered heterocycloalkyl group, and a 6-membered heterocycloalkyl group. R Ｂ However, hydrogen, -C １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -S(O) ２ R Ｂ１ , -S(O)R Ｂ１ , -C(O)R Ｂ１ , -C(O)OR Ｂ１ Selected from the group consisting of, Each R Ｂ１ However, each independently, hydrogen and -C １～６ Alkyl and halogen-substituted -C １～６ Selected from the group consisting of alkyl groups, R 10 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group).

5. The compound according to claim 4, characterized in that the A ring is selected from the group consisting of formula 19.

6. A compound represented by formula 1, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Here, R1 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR11, -C0-4 alkylene group -NR12, R12] R 11 is selected from the group consisting of -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Each R12 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. The C ring is selected from the group consisting of equation 2, X1, X2, and X4 are each independently selected from the group consisting of N and CR4. X 3 is selected from the group consisting of N and CR 3. X 5 is selected from the group consisting of O, S, and NR 4. X 6 is selected from the group consisting of CR 4 and N. X 8 is selected from the group consisting of CR 4 R 4 and O. X 7 is selected from the group consisting of S and NR 4. X 9 is selected from the group consisting of CR 4 R 4, R2 is selected from the group consisting of equation 3, R21 and R22 are each independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR24, -C0-4 alkylene group -NR24, R24. Each R 24 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R21 and R22, together with the atoms they are linked to, form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or a group of formula 4. R 23 is hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -C(O)R 25, -C0-4 alkylene group -C(O)NR 25 R 25, -C0-4 alkylene group -C(O)OR 25, -C0-4 alkylene group -S(O)2 R 25, -C0-4 alkylene group -S(O)R 25, -C0-4 alkylene group -S(O)(NH)R 25, -C0-4 alkylene group -S(O)2 NR 25 R 25, -C 0-4 alkylene group -S(O)NR 25 R 25, -C 0-4 alkylene group -S(O)(NH)NR 25 R 25, -C 0-4 alkylene group -OR 25, -C 0-4 alkylene group -OC(O)R 25, -C 0-4 alkylene group -OS(O) 2 R 25, -C 0-4 alkylene group -OS(O)R 25, -C 0-4 alkylene group -NR 25 R 25, -C 0-4 alkylene group -NR 25 C(O)R 25, -C 0-4 alkylene group -NR 25 S(O) 2 R 25, -C 0-4 Selected from the group consisting of alkylene group -NR 25 S(O)R 25, -C 0 to 4, and alkylene group -NR 25 S(O)(NH)R 25. Each R 25 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R23 and R3, together with the atoms they are linked to, form a 4-8 membered carbocyclyl group and a 4-8 membered heterocycloalkyl group, respectively. R3 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, hydroxy-substituted -C1-6 alkyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group), Each R4 is independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group). R5 is selected from the group consisting of hydrogen and -C1-C6 alkyl groups. Ring A is selected from the group consisting of equation 20, Y １ , Y ２ , Y ４ However, N and CR are independent of each other. Ｙ Selected from the group consisting of, Each R Ｙ However, each is independent of hydrogen, halogen, cyano group, and -C. １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, R Ｂ However, hydrogen, -C １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -S(O) ２ R Ｂ１ , -S(O)R Ｂ１ , -C(O)R Ｂ１ , -C(O)OR Ｂ１ Selected from the group consisting of, Each R Ｂ１ However, each independently, hydrogen and -C １～６ Alkyl and halogen-substituted -C １～６ Selected from the group consisting of alkyl groups, Y ５ However, chemical bonds, O, S, NR Ｙ５１ CR Ｙ５１ R Ｙ５１ Selected from the group consisting of, Each R Ｙ５１ However, each independently, hydrogen and -C １～６ Selected from the group consisting of alkyl groups, R 10 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group).

7. The compound according to claim 6, characterized in that the A ring is selected from the group consisting of formula 21.

8. A compound represented by formula 1, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Here, R1 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR11, -C0-4 alkylene group -NR12, R12] R 11 is selected from the group consisting of -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Each R12 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. The C ring is selected from the group consisting of equation 2, X1, X2, and X4 are each independently selected from the group consisting of N and CR4. X 3 is selected from the group consisting of N and CR 3. X 5 is selected from the group consisting of O, S, and NR 4. X 6 is selected from the group consisting of CR 4 and N. X 8 is selected from the group consisting of CR 4 R 4 and O. X 7 is selected from the group consisting of S and NR 4. X 9 is selected from the group consisting of CR 4 R 4, R2 is selected from the group consisting of equation 3, R21 and R22 are each independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR24, -C0-4 alkylene group -NR24, R24. Each R 24 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R21 and R22, together with the atoms they are linked to, form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or a group of formula 4. R 23 is hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -C(O)R 25, -C0-4 alkylene group -C(O)NR 25 R 25, -C0-4 alkylene group -C(O)OR 25, -C0-4 alkylene group -S(O)2 R 25, -C0-4 alkylene group -S(O)R 25, -C0-4 alkylene group -S(O)(NH)R 25, -C0-4 alkylene group -S(O)2 NR 25 R 25, -C 0-4 alkylene group -S(O)NR 25 R 25, -C 0-4 alkylene group -S(O)(NH)NR 25 R 25, -C 0-4 alkylene group -OR 25, -C 0-4 alkylene group -OC(O)R 25, -C 0-4 alkylene group -OS(O) 2 R 25, -C 0-4 alkylene group -OS(O)R 25, -C 0-4 alkylene group -NR 25 R 25, -C 0-4 alkylene group -NR 25 C(O)R 25, -C 0-4 alkylene group -NR 25 S(O) 2 R 25, -C 0-4 Selected from the group consisting of alkylene group -NR 25 S(O)R 25, -C 0 to 4, and alkylene group -NR 25 S(O)(NH)R 25. Each R 25 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R23 and R3, together with the atoms they are linked to, form a 4-8 membered carbocyclyl group and a 4-8 membered heterocycloalkyl group, respectively. R3 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, hydroxy-substituted -C1-6 alkyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group), Each R4 is independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group). R5 is selected from the group consisting of hydrogen and -C1-C6 alkyl groups. Ring A is selected from the group consisting of equation 22, However, it represents a single bond or a double bond. Y １ , Y ２ , Y ４ However, N and CR are independent of each other. Ｙ Selected from the group consisting of, Each R Ｙ However, each is independent of hydrogen, halogen, cyano group, and -C. １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, R Ｂ However, hydrogen, -C １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -S(O) ２ R Ｂ１ , -S(O)R Ｂ１ , -C(O)R Ｂ１ , -C(O)OR Ｂ１ Selected from the group consisting of, Each R Ｂ１ However, each independently, hydrogen and -C １～６ Alkyl and halogen-substituted -C １～６ Selected from the group consisting of alkyl groups, Y ５ , Y ６ However, each is independent of the chemical bond, -C ０～１ Alkylene groups -O-, -C ０～１ Alkylene groups -S-, -C ０～１ Alkylene group - NR Ｙ５１ -, CR Ｙ５１ R Ｙ５１ Selected from the group consisting of, Each R Ｙ５１ However, each independently, hydrogen and -C １～６ Selected from the group consisting of alkyl groups, R 10 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group).

9. The compound according to claim 8, characterized in that the A ring is selected from the group consisting of formula 23.

10. A compound represented by formula 1, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Here, R1 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR11, -C0-4 alkylene group -NR12, R12] R 11 is selected from the group consisting of -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Each R12 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. The C ring is selected from the group consisting of equation 2, X1, X2, and X4 are each independently selected from the group consisting of N and CR4. X 3 is selected from the group consisting of N and CR 3. X 5 is selected from the group consisting of O, S, and NR 4. X 6 is selected from the group consisting of CR 4 and N. X 8 is selected from the group consisting of CR 4 R 4 and O. X 7 is selected from the group consisting of S and NR 4. X 9 is selected from the group consisting of CR 4 R 4, R2 is selected from the group consisting of equation 3, R21 and R22 are each independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR24, -C0-4 alkylene group -NR24, R24. Each R 24 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R21 and R22, together with the atoms they are linked to, form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or a group of formula 4. R 23 is hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -C(O)R 25, -C0-4 alkylene group -C(O)NR 25 R 25, -C0-4 alkylene group -C(O)OR 25, -C0-4 alkylene group -S(O)2 R 25, -C0-4 alkylene group -S(O)R 25, -C0-4 alkylene group -S(O)(NH)R 25, -C0-4 alkylene group -S(O)2 NR 25 R 25, -C 0-4 alkylene group -S(O)NR 25 R 25, -C 0-4 alkylene group -S(O)(NH)NR 25 R 25, -C 0-4 alkylene group -OR 25, -C 0-4 alkylene group -OC(O)R 25, -C 0-4 alkylene group -OS(O) 2 R 25, -C 0-4 alkylene group -OS(O)R 25, -C 0-4 alkylene group -NR 25 R 25, -C 0-4 alkylene group -NR 25 C(O)R 25, -C 0-4 alkylene group -NR 25 S(O) 2 R 25, -C 0-4 Selected from the group consisting of alkylene group -NR 25 S(O)R 25, -C 0 to 4, and alkylene group -NR 25 S(O)(NH)R 25. Each R 25 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R23 and R3, together with the atoms they are linked to, form a 4-8 membered carbocyclyl group and a 4-8 membered heterocycloalkyl group, respectively. R3 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, hydroxy-substituted -C1-6 alkyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group), Each R4 is independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group). R5 is selected from the group consisting of hydrogen and -C1-C6 alkyl groups. Ring A is selected from the group consisting of equation 24, Y １ However, N, CR Ｙ Selected from the group consisting of, R Ｙ However, hydrogen, halogen, cyano group, -C １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -C ０～４ Alkylene groups -OH, -C ０～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - NH ２ , -C ０～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C ０～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, The B ring is selected from the group consisting of a 3- to 8-membered monocyclic carbocyclyl group and a 4- to 8-membered monocyclic heterocycloalkyl group, and the monocyclic carbocyclyl group and monocyclic heterocycloalkyl group are further divided into one, two, three, four or five R groups. Ｂ It may be replaced with, Each R Ｂ However, each is independent of hydrogen, halogen, cyano group, and -C. １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -OR Ｂ１ ,-SR Ｂ１ , -S(O) ２ R Ｂ１ , -S(O)R Ｂ１ , -C(O)R Ｂ１ , -C(O)OR Ｂ１ , -NR Ｂ１ R Ｂ１ A group consisting of, or two independent R Ｂ However, together with the atoms that connect to them, they form the group of formula 25, Each R Ｂ１ However, each independently, hydrogen and -C １～６ Alkyl and halogen-substituted -C １～６ Selected from the group consisting of alkyl groups, Y ７ However, O, S, NR Ｙ７１ Selected from the group consisting of, R Ｙ７１ However, hydrogen, -C １～６ Alkyl and halogen-substituted -C １～６ Alkyl alkyl group, -C １～４ Alkylene groups -OH, -C １～４ Alkylene group -O(C) １～６ Alkyl alkyl group), -C １～４ Alkylene group - NH ２ , -C １～４ Alkylene group - NH(C) １～６ Alkyl alkyl group), -C １～４ Alkylene group - N(C) １～６ (Alkyl alkyl group) (C １～６ Selected from the group consisting of alkyl groups, R 10 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group).

11. The compound according to claim 10, characterized in that the A ring is selected from the group consisting of formula 26.

12. A compound represented by formula 1, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Here, R1 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR11, -C0-4 alkylene group -NR12, R12] R 11 is selected from the group consisting of -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Each R12 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. The C ring is selected from the group consisting of equation 2, X1, X2, and X4 are each independently selected from the group consisting of N and CR4. X 3 is selected from the group consisting of N and CR 3. X 5 is selected from the group consisting of O, S, and NR 4. X 6 is selected from the group consisting of CR 4 and N. X 8 is selected from the group consisting of CR 4 R 4 and O. X 7 is selected from the group consisting of S and NR 4. X 9 is selected from the group consisting of CR 4 R 4, R2 is selected from the group consisting of equation 3, R21 and R22 are each independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OR24, -C0-4 alkylene group -NR24, R24. Each R 24 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R21 and R22, together with the atoms they are linked to, form a 3-8 membered carbocyacrylic group, a 4-8 membered heterocycloalkyl group, or a group of formula 4. R 23 is hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -C(O)R 25, -C0-4 alkylene group -C(O)NR 25 R 25, -C0-4 alkylene group -C(O)OR 25, -C0-4 alkylene group -S(O)2 R 25, -C0-4 alkylene group -S(O)R 25, -C0-4 alkylene group -S(O)(NH)R 25, -C0-4 alkylene group -S(O)2 NR 25 R 25, -C 0-4 alkylene group -S(O)NR 25 R 25, -C 0-4 alkylene group -S(O)(NH)NR 25 R 25, -C 0-4 alkylene group -OR 25, -C 0-4 alkylene group -OC(O)R 25, -C 0-4 alkylene group -OS(O) 2 R 25, -C 0-4 alkylene group -OS(O)R 25, -C 0-4 alkylene group -NR 25 R 25, -C 0-4 alkylene group -NR 25 C(O)R 25, -C 0-4 alkylene group -NR 25 S(O) 2 R 25, -C 0-4 Selected from the group consisting of alkylene group -NR 25 S(O)R 25, -C 0 to 4, and alkylene group -NR 25 S(O)(NH)R 25. Each R 25 is independently selected from the group consisting of hydrogen, -C1-6 alkyl groups, -C2-6 alkenyl groups, -C2-6 alkynyl groups, halogen-substituted -C1-6 alkyl groups, halogen-substituted -C2-6 alkenyl groups, and halogen-substituted -C2-6 alkynyl groups. Alternatively, R23 and R3, together with the atoms they are linked to, form a 4-8 membered carbocyclyl group and a 4-8 membered heterocycloalkyl group, respectively. R3 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, hydroxy-substituted -C1-6 alkyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group), Each R4 is independently selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group). R5 is selected from the group consisting of hydrogen and -C1-C6 alkyl groups. Ring A is selected from the group consisting of equation 28, R 10 is selected from the group consisting of hydrogen, halogen, cyano group, -C1-6 alkyl group, -C2-6 alkenyl group, -C2-6 alkynyl group, halogen-substituted -C1-6 alkyl group, halogen-substituted -C2-6 alkenyl group, halogen-substituted -C2-6 alkynyl group, -C0-4 alkylene group -OH, -C0-4 alkylene group -O (C1-6 alkyl group), -C0-4 alkylene group -NH2, -C0-4 alkylene group -NH (C1-6 alkyl group), and -C0-4 alkylene group -N (C1-6 alkyl group) (C1-6 alkyl group).

13. A compound selected from the group consisting of formula 29, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

14. Use of a compound according to any one of claims 1 to 13, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof in the manufacture of a Wee1 inhibitor.

15. Use of a compound according to any one of claims 1 to 13, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention and / or treatment of cancer.

16. A pharmaceutical composition comprising a compound according to any one of claims 1 to 13, a deuterium compound thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

17. Furthermore, the pharmaceutical composition according to claim 16, comprising a pharmacologically acceptable carrier, additive, or mediator.

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