Fused ring compounds and uses thereof

Abstract

FIELD OF THE INVENTION The present invention relates to fused ring compounds, compositions containing same, and uses thereof. JPEG2025540269000705.jpg56170

Description

[Technical Field]

[0001] The present invention relates to compounds that inhibit the activity of various forms of K-Ras protein, including wild-type and mutant forms of K-Ras, compositions containing the compounds, and methods of using the compounds. [Background technology]

[0002] There is an unmet need to develop novel multi-K-Ras inhibitors for the treatment of K-Ras-mediated cancers. Summary of the Invention [Means for solving the problem]

[0003] The present invention provides a compound represented by formula (I): [ka] The present invention provides a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof.

[0004] Here, the definitions of the respective variables are as follows:

[0005] The present invention further provides a pharmaceutical composition comprising a therapeutically effective amount of a compound as defined in the present invention and a pharmaceutically acceptable excipient.

[0006] The present invention further provides a method of treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound defined in the present invention, or a pharmaceutical composition.

[0007] The present invention further provides a method for treating cancer in a subject in need thereof, comprising (a) determining whether the cancer is associated with a K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-Ras G12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutation, and / or K-Ras wild-type amplification, and (b) if so, administering to the subject in need thereof a therapeutically effective amount of a compound defined in the present invention, or a pharmaceutical composition.

[0008] The present invention also provides a compound as defined in the present invention, or a pharmaceutical composition, for use in therapy.

[0009] The present invention also provides a compound as defined in the present invention for use as a medicament, or a pharmaceutical composition.

[0010] The present invention also provides a compound as defined herein, or a pharmaceutical composition, in a method for treating cancer.

[0011] The present invention also provides the use of a compound as defined in the present invention, or a pharmaceutical composition, in the treatment of cancer.

[0012] The present invention also provides the use of a compound or pharmaceutical composition as defined in the present invention in the preparation of a medicament for treating cancer. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention provides the following disclosure. [1]. A compound represented by formula (I), [ka] a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, where: X1, in each occurrence, independently represents a bond, -C(R X11 )(RX12 )-, -NR X13 -, -O-, -S-, -S(=O)-, or -S(=O)2-; R X11 or R X12 are independently hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -N(R A )2, -OR A , -SR A , -S(=O)R B , -S(=O)2R B , -C(=O)R B , -C(=O)OR B , -C(=O)N(R B )2, -S(=O)OR B , -S(=O)N(R B )2, -S(=O)2OR B , -S(=O)2N(R B )2, -P(=O)(R B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C2-6 Alkenyl group, -C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R C )2, -OR C , -SR C , -S(=O)R D , -S(=O)2R D , -C(=O)R D , -C(=O)OR C , -OC(=O)R D , -C(=O)N(R C )2, -NR C C(=O)R D , -OC(=O)OR C , -NR C C(=O)OR D , -OC(=O)N(R C )2, -NR C C(=O)N(R C )2, -S(=O)OR C , -OS(=O)R D , -S(=O)N(R C )2, -NR C S(=O)R D , -S(=O)2OR C , -OS(=O)2R D , -S(=O)2N(R C )2, -NR C S(=O)2R D , -OS(=O)2OR C , -NR C S(=O)2OR C , -OS(=O)2NR C , -NR C S(=O)2N(R C )2, -P(R C )2, -P(=O)(R D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, R X11 and R X12 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R SX1 is replaced by R X13 is hydrogen, deuterium, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -S(=O)R B , -S(=O)2R B , -C(=O)R B , -C(=O)OR B , -C(=O)N(R B )2, -S(=O)OR B , -S(=O)N(R B )2, -S(=O)2OR B , -S(=O)2N(R B )2, -P(=O)(R B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R C )2, -OR C , -SR C , -S(=O)R D , -S(=O)2R D , -C(=O)R D , -C(=O)OR C , -OC(=O)R D , -C(=O)N(R C )2, -NR C C(=O)R D , -OC(=O)OR C , -NR C C(=O)OR D , -OC(=O)N(R C )2, -NR C C(=O)N(R C )2, -S(=O)OR C , -OS(=O)R D , -S(=O)N(R C )2, -NR C S(=O)R D , -S(=O)2OR C , -OS(=O)2R D , -S(=O)2N(R C )2, -NR C S(=O)2R D , -OS(=O)2OR C , -NR C S(=O)2OR C , -OS(=O)2NR C , -NR C S(=O)2N(R C )2, -P(R C )2, -P(=O)(R D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; X2, in each occurrence, is independently N or CR1; R1 is hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R 1A )2, -OR 1A , -SR 1A , -S(=O)R 1B , -S(=O)2R 1B , -C(=O)R 1B , -C(=O)OR 1A , -OC(=O)R 1B , -C(=O)N(R 1A )2, -NR 1A C(=O)R 1B , -OC(=O)OR 1A , -NR 1A C(=O)OR 1A , -NR 1A C(=S)OR 1A , -OC(=O)N(R 1A )2, -NR 1A C(=O)N(R 1A )2, -S(=O)OR 1A , -OS(=O)R 1B , -S(=O)N(R 1A )2, -NR 1A S(=O)R 1B , -S(=O)2OR 1A , -OS(=O)2R 1B , -S(=O)2N(R 1A )2, -NR 1A S(=O)2R 1B , -OS(=O)2OR 1A , -NR 1A S(=O)2OR 1A , -OS(=O)2N(R 1A )2, -NR 1A S(=O)2N(R 1A )2, -P(R 1A )2, -P(=O)(R 1B2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R 1C )2, -OR 1C , -SR 1C , -S(=O)R 1D , -S(=O)2R 1D , -C(=O)R 1D , -C(=O)OR 1D , -OC(=O)R 1D , -C(=O)N(R 1C )2, -NR 1C C(=O)R 1D , -OC(=O)OR 1C , -NR 1C C(=O)OR 1C , -NR 1C C(=S)OR 1C , -OC(=O)N(R 1C )2, -NR 1C C(=O)N(R 1C )2, -S(=O)OR 1C , -OS(=O)R1D , -S(=O)N(R 1C )2, -NR 1C S(=O)R 1D , -S(=O)2OR 1C , -OS(=O)2R 1D , -S(=O)2N(R 1C )2, -NR 1C S(=O)2R 1D , -OS(=O)2OR 1C , -NR 1C S(=O)2OR 1C , -OS(=O)2N(R 1C )2, -NR 1C S(=O)2N(R 1C )2, -P(R 1C )2, -P(=O)(R 1D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; n1 is 0, 1, 2, 3, 4, 5, or 6; Ring A is a 3- to 20-membered heterocycle containing only an N atom bonded to the pyrimidine ring, or a 3- to 20-membered (e.g., 3- to 10-membered) heterocycle further containing one or more heteroatoms selected from O, S, S=O, and S(=O)2 in addition to the N atom bonded to the pyrimidine ring; R S1 are independently hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S1A )2, -OR S1A , -SR S1A , -S(=O)R S1B , -S(=O)2R S1B , -C(=O)R S1B , -C(=O)ORS1A , -OC(=O)R S1B , -C(=O)N(R S1A )2, -N S1A C(=O)R S1B , -OC(=O)OR S1A , -N S1A C(=O)OR S1A , -NR S1A C(=S)O S1A , -OC(=O)N(R S1A )2, -NR S1A C(=O)N(R S1A )2, -S(=O)OR S1A , -OS(=O)R S1B , -S(=O)N(R S1A )2, -NR S1A S(=O)R S1B , -S(=O)2OR S1A , -OS(=O)2R S1B , -S(=O)2N(R S1A )2, -NR S1A S(=O)2R S1B , -OS(=O)2OR S1A , -NR S1A S(=O)2OR S1A , -OS(=O)2N(R S1A )2, -NR S1A S(=O)2N(R S1A )2, -P(R S1A )2, -P(=O)(R S1B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S1C )2, -OR S1C , -SR S1C , -S(=O)R S1D , -S(=O)2R S1D , -C(=O)R S1D , -C(=O)OR S1C , -OC(=O)R S1D , -C(=O)N(R S1C )2, -NR S1C C(=O)R S1D , -OC(=O)OR S1C , -NR S1C C(=O)OR S1C , -NR S1C C(=S)OR S1C , -OC(=O)N(R S1C )2, -NR S1C C(=O)N(R S1C )2, -S(=O)OR S1C , -OS(=O)R S1D , -S(=O)N(R S1C )2, -NR S1C S(=O)R S1D , -S(=O)2OR S1C , -OS(=O)2R S1D , -S(=O)2N(R S1C )2, -NR S1C S(=O)2R S1D , -OS(=O)2OR S1C , -NR S1C S(=O)2OR S1C , -OS(=O)2N(R S1C)2, -NR S1C S(=O)2N(R S1C )2, -P(R S1C )2, -P(=O)(R S1D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R S1 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S11 is replaced by Optionally, two adjacent R S1 along with the atoms to which they are bonded, [ka] forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R S12 is replaced by Optionally, two non-adjacent R S1 are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or replaced by one or two heteroatoms selected from N, O, S, S=O, and S(=O)2, and the hydrogen on each carbon atom or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R S13 is replaced by m1 is 0, 1, 2, 3, 4, 5, 6, 7, 8, or 9; R S2 are independently hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S2A )2, -OR S2A , -SR S2A , -S(=O)R S2B , -S(=O)2R S2B , -C(=O)R S2B , -C(=O)OR S2A , -OC(=O)R S2B , -C(=O)N(R S2A )2, -NR S2A C(=O)R S2B , -OC(=O)OR S2A , -NR S2A C(=O)OR S2A , -NR S2A C(=S)OR S2A , -OC(=O)N(R S2A )2, -NR S2A C(=O)N(R S2A )2, -S(=O)OR S2A , -OS(=O)R S2B , -S(=O)N(R S2A )2, -NR S2A S(=O)R S2B , -S(=O)2OR S2A , -OS(=O)2R S2B , -S(=O)2N(R S2A )2, -NR S2A S(=O)2R S2B , -OS(=O)2OR S2A , -NR S2A S(=O)2OR S2A , -OS(=O)2N(R S2A )2, -NR S2A S(=O)2N(R S2A )2, -P(RS2A )2, -P(=O)(R S2B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S2C )2, -OR S2C , -SR S2C , -S(=O)R S2D , -S(=O)2R S2D , -C(=O)R S2D , -C(=O)OR S2D , -OC(=O)R S2D , -C(=O)N(R S2C )2, -NR S2C C(=O)R S2D , -OC(=O)OR S2C , -NR S2C C(=O)OR S2C , -NR S2C C(=S)OR S2C , -OC(=O)N(R S2C )2, -NR S2C C(=O)N(R S2C)2, -S(=O)OR S2C , -OS(=O)R S2D , -S(=O)N(R S2C )2, -NR S2C S(=O)R S2D , -S(=O)2OR S2C , -OS(=O)2R S2D , -S(=O)2N(R S2C )2, -NR S2C S(=O)2R S2D , -OS(=O)2OR S2C , -NR S2C S(=O)2OR S2C , -OS(=O)2N(R S2C )2, -NR S2C S(=O)2N(R S2C )2, -P(R S2C )2, -P(=O)(R S2D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R S2 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S21 is replaced by Optionally, two adjacent R S2 along with the atoms to which they are bonded, [ka] forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R S22 is replaced by Optionally, two non-adjacent R S2 are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or replaced by one or two heteroatoms selected from N, O, S, S=O, and S(=O)2, and the hydrogen on each carbon atom or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R S23 is replaced by m2 is 0, 1, 2, 3, 4, or 5; Y1 is a bond, O, S, S(=O), S(=O)2, or NR Y11 and R Y11 is hydrogen, deuterium, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -S(=O)R B , -S(=O)2R B , -C(=O)R B , -C(=O)OR B , -C(=O)N(R B )2, -S(=O)OR B , -S(=O)N(R B )2, -S(=O)2OR B , -S(=O)2N(R B )2, -P(=O)(R B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R C )2, -OR C , -SR C , -S(=O)R D , -S(=O)2R D , -C(=O)R D , -C(=O)OR C , -OC(=O)R D , -C(=O)N(R C )2, -NR C C(=O)R D , -OC(=O)OR C , -NR C C(=O)OR D , -OC(=O)N(R C )2, -NR C C(=O)N(R C )2, -S(=O)OR C , -OS(=O)R D , -S(=O)N(R C )2, -NR C S(=O)R D , -S(=O)2OR C , -OS(=O)2R D , -S(=O)2N(R C )2, -NR C S(=O)2R D , -OS(=O)2OR C , -NR C S(=O)2OR C , -OS(=O)2NR C , -NR C S(=O)2N(R C )2, -P(R C )2, -P(=O)(R D) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; R3 is [ka] and Each R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 38 , R 39 , R 310 , and R 311 are independently hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -N(R A )2, -OR A , -SR A , -S(=O)R B , -S(=O)2R B , -C(=O)R B , -C(=O)OR A , -C(=O)N(R A )2, -S(=O)OR A , -S(=O)N(R A )2, -S(=O)2OR A , -S(=O)2N(R A )2, -P(=O)(R B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R C )2, -OR C , -SR C , -S(=O)R D , -S(=O)2R D , -C(=O)R D , -C(=O)OR C , -OC(=O)R D , -C(=O)N(R C )2, -NR C C(=O)R D , -OC(=O)OR C , -NR C C(=O)OR D , -OC(=O)N(R C )2, -NR C C(=O)N(R C )2, -S(=O)OR C , -OS(=O)R D , -S(=O)N(R C )2, -NR C S(=O)R D , -S(=O)2OR C , -OS(=O)2R D , -S(=O)2N(R C )2, -NR C S(=O)2R D , -OS(=O)2OR C , -NR C S(=O)2OR C , -OS(=O)2NR C , -NR CS(=O)2N(R C )2, -P(R C )2, -P(=O)(R D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, R 31 and R 32 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S33 is replaced by Optionally, R 33 and R 34 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S34 is replaced by Optionally, R 35 and R 36 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S35 is replaced by Optionally, R 38 and R 39 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S310 is replaced by Optionally, R 310 and R 311 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S316 is replaced by n2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0, 1, 2, 3, 4, 5, or 6; n4 is 0, 1, 2, 3, 4, 5, or 6; n5 is 0, 1, 2, 3, 4, 5, or 6, n6 is 0, 1, 2, 3, 4, 5, or 6, Ring B is a 3-10 membered heterocycle, optionally further containing 1, 2, or 3 heteroatoms selected from N, O, S, S(=O), and S(=O)2; Ring C is a 3-10 membered heterocycle, optionally further containing 1, 2, or 3 heteroatoms selected from N, O, S, S(=O), and S(=O)2; Ring D is a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring; Ring I is a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring containing 1, 2, or 3 heteroatoms selected from N, O, S, S(═O), and S(═O)2; Ring J is a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring containing 1, 2, or 3 heteroatoms selected from N, O, S, S(═O), and S(═O)2; Ring K is a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring containing 1, 2, or 3 heteroatoms selected from N, O, S, S(═O), and S(═O)2; R S31 is hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S31A )2, -OR S31A , -SR S31A , -S(=O)R S31B , -S(=O)2R S31B , -C(=O)R S31B , -C(=O)OR S31A , -OC(=O)R S31B , -C(=O)N(R S31A )2, -NR S31A C(=O)R S31B , -OC(=O)OR S31A , -NR S31A C(=O)OR S31A , -NR S31AC(=S)OR S31A , -OC(=O)N(R S31A )2, -NR S31A C(=O)N(R S31A )2, -S(=O)OR S31A , -OS(=O)R S31B , -S(=O)N(R S31A )2, -NR S31A S(=O)R S31B , -S(=O)2OR S31A , -OS(=O)2R S31B , -S(=O)2N(R S31A )2, -NR S31A S(=O)2R S31B , -OS(=O)2OR S31A , -NR S31A S(=O)2OR S31A , -OS(=O)2N(R S31A )2, -NR S31A S(=O)2N(R S31A )2, -P(R S31A )2, -P(=O)(R S31B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S31C )2, -OR S31C , -SR S31C , -S(=O)R S31D , -S(=O)2R S31D , -C(=O)R S31D , -C(=O)OR S31C , -OC(=O)R S31D , -C(=O)N(R S31C )2, -NR S31C C(=O)R S31D , -OC(=O)OR S31C , -NR S31C C(=O)OR S31C , -NR S31C C(=S)OR S31C , -OC(=O)N(R S31C )2, -NR S31C C(=O)N(R S31C )2, -S(=O)OR S31C , -OS(=O)R S31D , -S(=O)N(R S31C )2, -NR S31C S(=O)R S31D , -S(=O)2OR S31C , -OS(=O)2R S31D , -S(=O)2N(R S31C )2, -NR S31C S(=O)2R S31D , -OS(=O)2OR S31C , -NR S31C S(=O)2OR S31C , -OS(=O)2N(R S31C )2, -NR S31C S(=O)2N(R S31C )2, -P(R S31C )2, -P(=O)(R S31D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R S31 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S311 is replaced by Optionally, two adjacent R S31 along with the atoms to which they are bonded, [ka] forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R S312 is replaced by Optionally, two non-adjacent R S31 are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or replaced by one or two heteroatoms selected from N, O, S, S=O, and S(=O)2, and the hydrogen on each carbon atom or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R S313 is replaced by m3 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12; R S32 is hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S32A )2, -OR S32A , -SR S32A , -S(=O)R S32B , -S(=O)2R S32B , -C(=O)R S32B , -C(=O)OR S32A , -OC(=O)R S32B , -C(=O)N(R S32A )2, -NR S32A C(=O)R S32B , -OC(=O)OR S32A , -NR S32A C(=O)OR S32A , -NR S32A C(=S)OR S32A , -OC(=O)N(R S32A )2, -NR S32A C(=O)N(R S32A )2, -S(=O)OR S32A , -OS(=O)R S32B , -S(=O)N(R S32A )2, -NR S32A S(=O)R S32B , -S(=O)2OR S32A , -OS(=O)2R S32B , -S(=O)2N(R S32A )2, -NR S32A S(=O)2R S32B , -OS(=O)2OR S32A , -NR S32A S(=O)2OR S32A , -OS(=O)2N(R S32A )2, -NR S32A S(=O)2N(R S32A )2, -P(R S32A )2, -P(=O)(R S32B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S32C )2, -OR S32C , -SR S32C , -S(=O)R S32C , -S(=O)2R S32D , -C(=O)R S32D , -C(=O)OR S32C , -OC(=O)R S32D , -C(=O)N(R S32C )2, -NR S32C C(=O)R S32D , -OC(=O)OR S32C , -NR S32C C(=O)OR S32C , -NR S32C C(=S)OR S32C , -OC(=O)N(R S32C )2, -NR S32C C(=O)N(R S32C )2, -S(=O)OR S32C , -OS(=O)R S32C , -S(=O)N(R S32C )2, -NR S32C S(=O)R S32D , -S(=O)2OR S32C , -OS(=O)2R S32D , -S(=O)2N(R S32C )2, -NR S32C S(=O)2R S32D , -OS(=O)2OR S32C , -NRS32C S(=O)2OR S32C , -OS(=O)2N(R S32C )2, -NR S32C S(=O)2N(R S32C )2, -P(R S32C )2, -P(=O)(R S32D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R S32 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S321 is replaced by Optionally, two adjacent R S32 along with the atoms to which they are bonded, [ka] forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R S322 is replaced by Optionally, two non-adjacent R S32are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or replaced by one or two heteroatoms selected from N, O, S, S=O, and S(=O)2, and the hydrogen on each carbon atom or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R S323 is replaced by m4 is 0, 1, 2, 3, 4, 5, or 6, R 37 is -N(R 37A ) a 2- or 3- to 10-membered heterocyclyl group, wherein said 3- to 10-membered heterocyclyl group optionally independently contains one or more R 37 is replaced by R S38 is hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S38A )2, -OR S38A , -SR S38A , -S(=O)R S38B , -S(=O)2R S38B , -C(=O)R S38B , -C(=O)OR S38A , -OC(=O)R S38B , -C(=O)N(R S38A )2, -NR S38A C(=O)R S38B , -OC(=O)OR S38A , -NR S38A C(=O)OR S38A , -NR S38A C(=S)OR S38A , -OC(=O)N(R S38A )2, -NR S38A C(=O)N(R S38A )2, -S(=O)ORS38A , -OS(=O)R S38B , -S(=O)N(R S38A )2, -NR S38A S(=O)R S38B , -S(=O)2OR S38A , -OS(=O)2R S38B , -S(=O)2N(R S38A )2, -NR S38A S(=O)2R S38B , -OS(=O)2OR S38A , -NR S38A S(=O)2OR S38A , -OS(=O)2N(R S38A )2, -NR S38A S(=O)2N(R S38A )2, -P(R S38A )2, -P(=O)(R S38B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S38C )2, -OR S38C , -SRS38C , -S(=O)R S38D , -S(=O)2R S38D , -C(=O)R S38D , -C(=O)OR S38C , -OC(=O)R S38D , -C(=O)N(R S38C )2, -NR S38C C(=O)R S38D , -OC(=O)OR S38C , -NR S38C C(=O)OR S38C , -NR S38C C(=S)OR S38C , -OC(=O)N(R S38C )2, -NR S38C C(=O)N(R S38C )2, -S(=O)OR S38C , -OS(=O)R S38D , -S(=O)N(R S38C )2, -NR S38C S(=O)R S38D , -S(=O)2OR S38C , -OS(=O)2R S38D , -S(=O)2N(R S38C )2, -NR S38C S(=O)2R S38D , -OS(=O)2OR S38C , -NR S38C S(=O)2OR S38C , -OS(=O)2N(R S38C )2, -NR S38C S(=O)2N(R S38C )2, -P(R S38C )2, -P(=O)(R S38D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R S38 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S381 is replaced by Optionally, two adjacent R S38 along with the atoms to which they are bonded, [ka] forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R S382 is replaced by Optionally, two non-adjacent R S38 are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or replaced by one or two heteroatoms selected from N, O, S, S=O, and S(=O)2, and the hydrogen on each carbon atom or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R S383 is replaced by m8 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, R S39 is hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S39A )2, -OR S39A , -SR S39A , -S(=O)RS39B , -S(=O)2R S39B , -C(=O)R S39B , -C(=O)OR S39A , -OC(=O)R S39B , -C(=O)N(R S39A )2, -NR S39A C(=O)R S39B , -OC(=O)OR S39A , -NR S39A C(=O)OR S39A , -NR S39A C(=S)OR S39A , -OC(=O)N(R S39A )2, -NR S39A C(=O)N(R S39A )2, -S(=O)OR S39A , -OS(=O)R S39B , -S(=O)N(R S39A )2, -NR S39A S(=O)R S39B , -S(=O)2OR S39A , -OS(=O)2R S39B , -S(=O)2N(R S39A )2, -NR S39A S(=O)2R S39B , -OS(=O)2OR S39A , -NR S39A S(=O)2OR S39A , -OS(=O)2N(R S39A )2, -NR S39A S(=O)2N(R S39A )2, -P(R S39A )2, -P(=O)(R S39B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S39C )2, -OR S39C , -SR S39C , -S(=O)R S39C , -S(=O)2R S39D , -C(=O)R S39D , -C(=O)OR S39C , -OC(=O)R S39D , -C(=O)N(R S39C )2, -NR S39C C(=O)R S39D , -OC(=O)OR S39C , -NR S39C C(=O)OR S39C , -NR S39C C(=S)OR S39C , -OC(=O)N(R S39C )2, -NR S39C C(=O)N(R S39C )2, -S(=O)OR S39C , -OS(=O)R S39C , -S(=O)N(R S39C )2, -NR S39C S(=O)R S39D , -S(=O)2OR S39C , -OS(=O)2R S39D , -S(=O)2N(R S39C )2, -NR S39C S(=O)2R S39D , -OS(=O)2OR S39C , -NR S39C S(=O)2OR S39C , -OS(=O)2N(R S39C)2, -NR S39C S(=O)2N(R S39C )2, -P(R S39C )2, -P(=O)(R S39D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R S39 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S391 is replaced by Optionally, two adjacent R S39 along with the atoms to which they are bonded, [ka] forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R S392 is replaced by Optionally, two non-adjacent R S39 are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or replaced by one or two heteroatoms selected from N, O, S, S=O, and S(=O)2, and the hydrogen on each carbon atom or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R S393 is replaced by m9 is 0, 1, 2, 3, 4, 5, or 6, R S315 is hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S315A )2, -OR S315A , -SR S315A , -S(=O)R S315B , -S(=O)2R S315B , -C(=O)R S315B , -C(=O)OR S315A , -OC(=O)R S315B , -C(=O)N(R S315A )2, -NR S315A C(=O)R S315B , -OC(=O)OR S315A , -NR S315A C(=O)OR S315A , -NR S315A C(=S)OR S315A , -OC(=O)N(R S315A )2, -NR S315A C(=O)N(R S315A )2, -S(=O)OR S315A , -OS(=O)R S315B , -S(=O)N(R S315A )2, -NR S315A S(=O)R S315B , -S(=O)2OR S315A , -OS(=O)2R S315B , -S(=O)2N(R S315A )2, -NR S315A S(=O)2R S315B , -OS(=O)2OR S315A , -NR S315A S(=O)2OR S315A , -OS(=O)2N(R S315A )2, -NR S315A S(=O)2N(R S315A )2, -P(R S315A)2, -P(=O)(R S315B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S315C )2, -OR S315C , -SR S315C , -S(=O)R S315C , -S(=O)2R S315D , -C(=O)R S315D , -C(=O)OR S315C , -OC(=O)R S315D , -C(=O)N(R S315C )2, -NR S315C C(=O)R S315D , -OC(=O)OR S315C , -NR S315C C(=O)OR S315C , -NR S315C C(=S)OR S315C , -OC(=O)N(R S315C )2, -NR S315C C(=O)N(R S315C )2, -S(=O)ORS315C , -OS(=O)R S315C , -S(=O)N(R S315C )2, -NR S315C S(=O)R S315D , -S(=O)2OR S315C , -OS(=O)2R S315D , -S(=O)2N(R S315C )2, -NR S315C S(=O)2R S315D , -OS(=O)2OR S315C , -NR S315C S(=O)2OR S315C , -OS(=O)2N(R S315C )2, -NR S315C S(=O)2N(R S315C )2, -P(R S315C )2, -P(=O)(R S315D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R S315 together with the carbon atoms bonded to both of these, [ka] Form a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [ka] The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R S3151 is replaced by Optionally, two adjacent R S315 along with the atoms to which they are bonded, [ka] forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R S3152 is replaced by Optionally, two non-adjacent R S315 are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or replaced by one or two heteroatoms selected from N, O, S, S=O, and S(=O)2, and the hydrogen on each carbon atom or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R S3153 is replaced by m 10 is 0, 1, 2, 3, 4, 5, or 6, R4 is a 6- to 10-membered aryl group, a 5- to 10-membered heteroaryl group, [ka] wherein the 6- to 10-membered aryl group, the 5- to 10-membered heteroaryl group, [ka] is independently unsubstituted or contains one or more R S4 is replaced by Z, in each occurrence, is independently C or N; when Z is C, ring E in each occurrence is independently a 6-membered aromatic ring or a 5- to 6-membered heteroaromatic ring, and ring F in each occurrence is independently a 3- to 10-membered carbocycle or a 3- to 10-membered heterocycle; when Z is N, ring E in each occurrence is independently a 5- to 6-membered heteroaromatic ring, and ring F in each occurrence is independently a 3- to 10-membered heterocyclic ring; R S4 are independently deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S4A )2, -OR S4A , -SR S4A , -S(=O)R S4B , -S(=O)2R S4B , -C(=O)R S4B , -C(=O)OR S4A , -OC(=O)R S4B , -C(=O)N(R S4A )2, -NR S4A C(=O)R S4B , -OC(=O)OR S4A , -NR S4A C(=O)OR S4A , -NR S4A C(=S)OR S4A , -OC(=O)N(R S4A )2, -NR S4A C(=O)N(R S4A )2, -S(=O)OR S4A , -OS(=O)R S4B , -S(=O)N(R S4A )2, -NR S4A S(=O)R S4B , -S(=O)2OR S4A , -OS(=O)2R S4B , -S(=O)2N(R S4A )2, -NR S4A S(=O)2R S4B , -OS(=O)2OR S4A , -NR S4A S(=O)2OR S4A , -OS(=O)2N(R S4A )2, -NR S4A S(=O)2N(R S4A )2, -P(R S4A )2, -P(=O)(R S4B2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R S4C )2, -OR S4C , -SR S4C , -S(=O)R S4D , -S(=O)2R S4D , -C(=O)R S4D , -C(=O)OR S4D , -OC(=O)R S4D , -C(=O)N(R S4C )2, -NR S4C C(=O)R S4D , -OC(=O)OR S4C , -NR S4C C(=O)OR S4C , -NR S4C C(=S)OR S4C , -OC(=O)N(R S4C )2, -NR S4C C(=O)N(R S4C )2, -S(=O)OR S4C , -OS(=O)RS4D , -S(=O)N(R S4C )2, -NR S4C S(=O)R S4D , -S(=O)2OR S4C , -OS(=O)2R S4D , -S(=O)2N(R S4C )2, -NR S4C S(=O)2R S4D , -OS(=O)2OR S4C , -NR S4C S(=O)2OR S4C , -OS(=O)2N(R S4C )2, -NR S4C S(=O)2N(R S4C )2, -P(R S4C )2, -P(=O)(R S4D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; R5 is hydrogen, deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R 5A )2, -OR 5A , -SR 5A , -S(=O)R 5B , -S(=O)2R 5B , -C(=O)R 5B , -C(=O)OR 5A , -OC(=O)R 5B , -C(=O)N(R 5A )2, -NR 5A C(=O)R 5B , -OC(=O)OR 5A , -NR 5A C(=O)OR 5A , -NR 5A C(=S)OR5A , -OC(=O)N(R 5A )2, -NR 5A C(=O)N(R 5A )2, -S(=O)OR 5A , -OS(=O)R 5B , -S(=O)N(R 5A )2, -NR 5A S(=O)R 5B , -S(=O)2OR 5A , -OS(=O)2R 5B , -S(=O)2N(R 5A )2, -NR 5A S(=O)2R 5B , -OS(=O)2OR 5A , -NR 5A S(=O)2OR 5A , -OS(=O)2N(R 5A )2, -NR 5A S(=O)2N(R 5A )2, -P(R 5A )2, -P(=O)(R 5B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6Alkynyl group, halogenated C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R 5C )2, -OR 5C , -SR 5C , -S(=O)R 5D , -S(=O)2R 5D , -C(=O)R 5D , -C(=O)OR 5D , -OC(=O)R 5D , -C(=O)N(R 5C )2, -NR 5C C(=O)R 5D , -OC(=O)OR 5C , -NR 5C C(=O)OR 5C , -NR 5C C(=S)OR 5C , -OC(=O)N(R 5C )2, -NR 5C C(=O)N(R 5C )2, -S(=O)OR 5C , -OS(=O)R 5D , -S(=O)N(R 5C )2, -NR 5C S(=O)R 5D , -S(=O)2OR 5C , -OS(=O)2R 5D , -S(=O)2N(R 5C )2, -NR 5C S(=O)2R 5D , -OS(=O)2OR 5C , -NR 5C S(=O)2OR 5C , -OS(=O)2N(R 5C )2, -NR 5C S(=O)2N(R 5C )2, -P(R 5C )2, -P(=O)(R 5D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Each R 1A , R 1C , R S1A, R S1C , R S2A , R S2C , R S31A , R S31C , R S32A , R S32C , R 37A , R S38A , R S38C , R S39A , R S39C , R S315A , R S315C , R S4A , R S4C , R 5A , R 5C , R a , R b , R c , R d , R e , R f , R g , R h , R i , R j , R k , and R l are independently hydrogen, deuterium, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -S(=O)R B , -S(=O)2R B , -C(=O)R B , -C(=O)OR B , -C(=O)N(R B )2, -S(=O)OR B , -S(=O)N(R B )2, -S(=O)2OR B , -S(=O)2N(R B )2, -P(=O)(R B 2) a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein the —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R C )2, -OR C , -SR C , -S(=O)R D , -S(=O)2R D , -C(=O)R D , -C(=O)OR C , -OC(=O)R D , -C(=O)N(R C )2, -NR C C(=O)R D , -OC(=O)OR C , -NR C C(=O)OR D , -OC(=O)N(R C )2, -NR C C(=O)N(R C )2, -S(=O)OR C , -OS(=O)R D , -S(=O)N(R C )2, -NR C S(=O)R D , -S(=O)2OR C , -OS(=O)2R D , -S(=O)2N(R C )2, -NR C S(=O)2R D , -OS(=O)2OR C , -NR C S(=O)2OR C , -OS(=O)2NR C , -NR C S(=O)2N(R C )2, -P(R C )2, -P(=O)(R D) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R 1A , two R 1C , two R S1A , two R S1C , two R S2A , two R S2C , two R S31A , two R S31C , two R S32A , two R S32C , two R 37A , two R S38A , two R S38C , two R S39A , two R S39C , two R S315A , two R S315C , two R S4A , two R S4C , two R 5A , or two R 5C together with the nitrogen atom to which they are both bonded, form a 3- to 10-membered heterocyclic ring or a 5- to 10-membered heteroaromatic ring, wherein the 3- to 10-membered heterocyclic ring or the 5- to 10-membered heteroaromatic ring is independently unsubstituted or substituted with one or more R SS is replaced by Each R 1B , R 1D , R S1B , R S1D , R S2B , R S2D , R S31B , R S31D , R S32B , R S32D , R S38B , R S38D , R S39B , R S315B , R S315D , R S39D , R S4B , R S4D , R 5B , and R 5D are independently hydrogen, deuterium, -C 1-6Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -N(R A )2, -OR A , -SR A , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R C )2, -OR C , -SR C , -S(=O)R D , -S(=O)2R D , -C(=O)R D , -C(=O)OR C , -OC(=O)R D , -C(=O)N(R C )2, -NR C C(=O)R D , -OC(=O)OR C , -NR C C(=O)OR D , -OC(=O)N(R C )2, -NRC C(=O)N(R C )2, -S(=O)OR C , -OS(=O)R D , -S(=O)N(R C )2, -NR C S(=O)R D , -S(=O)2OR C , -OS(=O)2R D , -S(=O)2N(R C )2, -NR C S(=O)2R D , -OS(=O)2OR C , -NR C S(=O)2OR C , -OS(=O)2NR C , -NR C S(=O)2N(R C )2, -P(R C )2, -P(=O)(R D ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Each R A , R B , R C , and R D are independently hydrogen, deuterium, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 an alkynyl group, a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with one or more R SA is replaced by Each R SX1 , R S11 , R S12 , R S13 , R S21 , R S22 , R S23 , R S33 , R S34 , R S35 , R S37 , R S310 , R S316 , R S311 , R S312 , R S313 , R S321 , R S322 , R S323 , R S381 , R S382 , R S383 , R S391 , R S392 , R S393 , R S3151 , R S3152 , R S3153 , R SS , and R SA are independently deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl groups, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl group), -OH, -O(C 1-6 alkyl group), -SH, -S(C 1-6 alkyl group), -S(=O)(C 1-6 alkyl group), -S(=O)2(C 1-6 alkyl group), -C(=O)(C 1-6 alkyl group), -C(=O)OH, -C(=O)(OC 1-6alkyl group), -OC(=O)(C 1-6 alkyl group), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl group), -C(=O)N(C 1-6 alkyl group)2, -NHC(=O)(C 1-6 alkyl group), -N(C 1-6 alkyl group)C(=O)(C 1-6 alkyl group), -OC(=O)O(C 1-6 alkyl group), -NHC(=O)(OC 1-6 alkyl group), -N(C 1-6 alkyl group)C(=O)(OC 1-6 alkyl group), -OC(=O)NH(C 1-6 alkyl group), -OC(=O)N(C 1-6 alkyl group), -NHC(=O)NH2, -NHC(=O)NH(C 1-6 alkyl group), -NHC(=O)N(C 1-6 alkyl group)2, -N(C 1-6 alkyl group)C(=O)NH2, -N(C 1-6 alkyl group)C(=O)NH(C 1-6 alkyl group), -N(C 1-6 alkyl group)C(=O)N(C 1-6 alkyl group)2, -S(=O)(OC 1-6 alkyl group), -OS(=O)(C 1-6 alkyl group), -S(=O)NH2, -S(=O)NH(C 1-6 alkyl group), -S(=O)N(C 1-6 alkyl group)2, -NHS(=O)(C 1-6 alkyl group), -N(C 1-6 alkyl group)S(=O)(C 1-6 alkyl group), -S(=O)2(OC 1-6 alkyl group), -OS(=O)2(C 1-6 alkyl group), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl group), -S(=O)2N(C 1-6 alkyl group), -NHS(=O)(C 1-6 alkyl group), -N(C 1-6 alkyl group)S(=O)2(C 1-6alkyl group), -OS(=O)2O(C 1-6 alkyl group), -NHS(=O)2O(C 1-6 alkyl group), -N(C 1-6 alkyl group)S(=O)2O(C 1-6 alkyl group), -OS(=O)2NH2, -OS(=O)2NH(C 1-6 alkyl group), -OS(=O)2N(C 1-6 alkyl group), -NHS(=O)2NH2, -NHS(=O)2NH(C 1-6 alkyl group), -NHS(=O)N(C 1-6 alkyl group)2, -N(C 1-6 alkyl group)S(=O)2NH2, -N(C 1-6 alkyl group)S(=O)2NH(C 1-6 alkyl group), -N(C 1-6 alkyl group)S(=O)2N(C 1-6 alkyl group)2, -PH(C 1-6 alkyl group), -P(C 1-6 alkyl group)2, -P(=O)H(C 1-6 alkyl group), -P(=O)(C 1-6 alkyl group) 2, 3 to 10-membered cycloalkyl group, 3 to 10-membered cycloalkenyl group, 3 to 10-membered cycloalkynyl group, 3 to 10-membered heterocyclyl group, 6 to 10-membered aryl group, or 5 to 10-membered heteroaryl group, wherein the above-mentioned -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-3 Alkyl groups, halogenated C 1-3 Alkyl groups, halogenated C 1-3 Alkoxy group, -C 2-3 Alkenyl group, -C 2-3Alkynyl groups, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-3 alkyl group), -N(C 1-3 alkyl group), -OH, -O(C 1-3 alkyl group), -SH, -S(C 1-3 alkyl group), -S(=O)(C 1-3 alkyl group), -S(=O)2(C 1-3 alkyl group), -C(=O)(C 1-3 alkyl group), -C(=O)OH, -C(=O)(OC 1-3 alkyl group), -OC(=O)(C 1-3 alkyl group), -C(=O)NH2, -C(=O)NH(C 1-3 alkyl group), -C(=O)N(C 1-3 alkyl group)2, -NHC(=O)(C 1-3 alkyl group), -N(C 1-3 alkyl group)C(=O)(C 1-3 alkyl group), -OC(=O)O(C 1-3 alkyl group), -NHC(=O)(OC 1-3 alkyl group), -N(C 1-3 alkyl group)C(=O)(OC 1-3 alkyl group), -OC(=O)NH(C 1-3 alkyl group), -OC(=O)N(C 1-3 alkyl group), -NHC(=O)NH2, -NHC(=O)NH(C 1-3 alkyl group), -NHC(=O)N(C 1-3 alkyl group)2, -N(C 1-3 alkyl group)C(=O)NH2, -N(C 1-3 alkyl group)C(=O)NH(C 1-3 alkyl group), -N(C 1-3 alkyl group)C(=O)N(C 1-3 alkyl group)2, -S(=O)(OC 1-3 alkyl group), -OS(=O)(C 1-3 alkyl group), -S(=O)NH2, -S(=O)NH(C 1-3 alkyl group), -S(=O)N(C 1-3 alkyl group)2, -NHS(=O)(C 1-3 alkyl group), -N(C 1-3alkyl group)S(=O)(C 1-3 alkyl group), -S(=O)2(OC 1-3 alkyl group), -OS(=O)2(C 1-3 alkyl group), -S(=O)2NH2, -S(=O)2NH(C 1-3 alkyl group), -S(=O)2N(C 1-3 alkyl group), -NHS(=O)(C 1-3 alkyl group), -N(C 1-3 alkyl group)S(=O)2(C 1-3 alkyl group), -OS(=O)2O(C 1-3 alkyl group), -NHS(=O)2O(C 1-3 alkyl group), -N(C 1-3 alkyl group)S(=O)2O(C 1-3 alkyl group), -OS(=O)2NH2, -OS(=O)2NH(C 1-3 alkyl group), -OS(=O)2N(C 1-3 alkyl group), -NHS(=O)2NH2, -NHS(=O)2NH(C 1-3 alkyl group), -NHS(=O)N(C 1-3 alkyl group)2, -N(C 1-3 alkyl group)S(=O)2NH2, -N(C 1-3 alkyl group)S(=O)2NH(C 1-3 alkyl group), -N(C 1-3 alkyl group)S(=O)2N(C 1-3 alkyl group)2, -PH(C 1-3 alkyl group), -P(C 1-3 alkyl group)2, -P(=O)H(C 1-3 alkyl group), -P(=O)(C 1-3 alkyl group) substituted with one or more substituents selected from 2, 3- to 10-membered cycloalkyl groups, 3- to 10-membered cycloalkenyl groups, 3- to 10-membered cycloalkynyl groups, 3- to 10-membered heterocyclyl groups, 6- to 10-membered aryl groups, and 5- to 10-membered heteroaryl groups; each heterocyclyl group or heterocycle, at each occurrence, contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, S(=O), and S(=O)2; each heteroaryl group, at each occurrence, contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S; A compound, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof.

[0014] [2] The compound according to [1], wherein the compound is represented by any one of the following formulas: [ka]

[0015] [3] R1 is hydrogen, deuterium, halogen, -CN, -OC 1-6 Alkyl group, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 an alkynyl group or a 3- to 6-membered cycloalkyl group, and 1-6 Alkyl group, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group or the 3- to 6-membered cycloalkyl group may be unsubstituted or may be substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 The compound according to [1] or [2], which is substituted with 1, 2, or 3 substituents selected from alkyl groups.

[0016] In some embodiments, R1 is [ka] is.

[0017] In some embodiments, R1 is hydrogen, deuterium, -F, -Cl, -Br, -CN, -OCH3, -CF3, -CH2CH2CN, a methyl group, an ethyl group, or a cyclopropyl group.

[0018] In some embodiments, R1 is [ka] is.

[0019] In some embodiments, R1 is -NO2.

[0020] In some embodiments, R1 is -Cl, [ka] -H or -F.

[0021] [4] The compound according to any one of [1] to [3], wherein R1 is hydrogen, deuterium, -F, -Cl, -Br, -CN, -OCH3, -CF3, -CH2CH2CN, a methyl group, an ethyl group, or a cyclopropyl group.

[0022] [5]. X1, in each occurrence, independently represents -C(R X11 )(R X12 )-, -NR X13 -, -O-, -S-, or -S(=O)-; R X11 or R X12 are independently hydrogen, deuterium, halogen, -C 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 The alkyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; Optionally, R X11 and R X12 together with the carbon atoms bonded to both of these, [ka] wherein the above-mentioned [ka] are independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; R X13 is hydrogen, deuterium, -C 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 The alkyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; The compound according to any one of [1] to [4].

[0023] In some embodiments, R X13 are -CH3, -CD3, [ka] -CH2CH3, -C(=O)CH3, or -CH2CH2CF3.

[0024] [6].R X11 or R X12 are independently hydrogen, deuterium, -F, methyl, -CD3, ethyl, propyl, isopropyl, or cyclopropyl; Optionally, R X11 and R X12 together with the carbon atoms bonded to both of these, [ka] Forming R X13 are independently hydrogen, deuterium, methyl, -CD3, ethyl, propyl, isopropyl, or cyclopropyl; The compound according to any one of [1] to [5].

[0025] [7].X1 is -CH2-, -CD2-, [ka] -O-, -S-, -S(=O)-, -NH-, -N(CH3)-, or -N(CD3)-; The compound according to any one of [1] to [6].

[0026] In some embodiments, X1 is -CH2-. In some embodiments, X1 is -CD2-. In some embodiments, X1 is [ka] In some embodiments, X1 is [ka] In some embodiments, X1 is -O-. In some embodiments, X1 is -S-. In some embodiments, X1 is -S(=O)-. In some embodiments, X1 is -NH- or -N(CH3)-. In some embodiments, X1 is -O- or -N(CH3)-. In some embodiments, X1 is -O- or -N(CD3)-. In some embodiments, X1 is -N(CH3)-. In some embodiments, X1 is -N(CD3)-. In some embodiments, X1 is -S(=O)2-.

[0027] [8] The compound according to any one of [1] to [7], wherein n1 is 0, 1, 2, or 3.

[0028] In some embodiments, n1 is 0, 1, or 2. In some embodiments, n1 is 0 or 1. In some embodiments, n1 is 0. In some embodiments, n1 is 1. In some embodiments, n1 is 2. In some embodiments, n1 is 3. In some embodiments, X1 is -O- and n1 is 0. In some embodiments, X1 is -O- and n1 is 1. In some embodiments, X1 is -O- and n1 is 2. In some embodiments, X1 is -O- and n1 is 3. In some embodiments, X1 is -NCH3- and n1 is 0. In some embodiments, X1 is -NCH3- and n1 is 1. In some embodiments, X1 is -NCH3- and n1 is 2. In some embodiments, X1 is -NCH3- and n1 is 3. In some embodiments, X1 is -CH2- and n1 is 0. In some embodiments, X1 is -CH2- and n1 is 1. In some embodiments, X1 is -CH2- and n1 is 2. In some embodiments, X1 is -CH2- and n1 is 3. In some embodiments, X1 is -CD2- and n1 is 0. In some embodiments, X1 is -CD2- and n1 is 1. In some embodiments, X1 is -CD2- and n1 is 2. In some embodiments, X1 is -CD2- and n1 is 3. In some embodiments, X1 is [ka] and n1 is 0. In some embodiments, X1 is [ka] and n1 is 1. In some embodiments, X1 is [ka] and n1 is 2. In some embodiments, X1 is [ka] and n1 is 3. In some embodiments, X1 is [ka] and n1 is 0. In some embodiments, X1 is [ka] and n1 is 1. In some embodiments, X1 is [ka] and n1 is 2. In some embodiments, X1 is [ka] and n1 is 3. In some embodiments, X1 is -NCD3- and n1 is 0. In some embodiments, X1 is -NCD3- and n1 is 1. In some embodiments, X1 is -NCD3- and n1 is 2. In some embodiments, X1 is -NCD3- and n1 is 3.

[0029] [9] The compound according to any one of [1] to [8], wherein m2 is 0, 1, 2, 3, 4, 5, or 6.

[0030] In some embodiments, m2 is 0, 1, 2, 3, 4, or 5. In some embodiments, m2 is 0, 1, 2, 3, or 4. In some embodiments, m2 is 0, 1, 2, or 3. In some embodiments, m2 is 0, 1, or 2. In some embodiments, m2 is 0 or 1. In some embodiments, m2 is 0. In some embodiments, m2 is 1. In some embodiments, m2 is 2. In some embodiments, m2 is 3. In some embodiments, m2 is 4. In some embodiments, m2 is 5. In some embodiments, m2 is 6.

[0031]

[10] The compound according to any one of the items [1] to [9], wherein the compound is represented by any one of the following formulas:

[0032] [ka]

[0033] [ka]

[0034]

[11] .R S2 is deuterium, halogen, or -C 1-6 alkyl group, wherein the —C 1-6 The alkyl groups are independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; Optionally, two adjacent R S2 along with the atoms to which they are bonded, [ka] forming a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, a benzene ring, or a 5- to 6-membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 The compound according to any one of [1] to

[10] , which is substituted with 1, 2, or 3 substituents selected from alkyl groups.

[0035]

[12] .R S2 is deuterium, -F, -CH3, or -CD3.

[0036] In some embodiments, R S2 is -CH3. In some embodiments, R S2 is deuterium.

[0037]

[13] . The compound according to any one of [1] to

[12] , wherein m1 is 0, 1, 2, 3, 4, 5, or 6.

[0038] In some embodiments, m1 is 0, 1, 2, 3, or 4. In some embodiments, m1 is 0, 1, 2, or 3. In some embodiments, m1 is 0, 1, or 2. In some embodiments, m1 is 0 or 1. In some embodiments, m1 is 0. In some embodiments, m1 is 1. In some embodiments, m1 is 2. In some embodiments, m1 is 3. In some embodiments, m1 is 4. In some embodiments, m1 is 5. In some embodiments, m1 is 6.

[0039]

[14] . The compound according to any one of [1] to

[13] , wherein ring A is a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered heterocycle containing only N atoms bonded to the pyrimidine ring, or a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered heterocycle further containing one or more heteroatoms selected from O, S, S=O, and S(=O)2 in addition to the N atoms bonded to the pyrimidine ring.

[0040] In some embodiments, ring A is a 3-10 (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered heterocycle containing only N atoms bonded to the pyrimidine ring, or a 3-10 (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered heterocycle containing one heteroatom selected from O, S, S=O, and S(=O)2, other than the N atom bonded to the pyrimidine ring. In some embodiments, ring A is a 3-10 (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered monocyclic heterocycle containing only N atoms bonded to the pyrimidine ring, a 3-10 (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered bicyclic heterocycle containing only N atoms bonded to the pyrimidine ring, a 3-10 (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered bridged ... a 10 (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered fused heterocycle; a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered spiroheterocycle containing only N atoms bonded to the pyrimidine ring; a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered monocyclic heterocycle further containing one heteroatom selected from O, S, S=O, and S(=O)2 other than the N atom bonded to the pyrimidine ring; a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered bicyclic heterocycle further containing one heteroatom selected from O, S, S=O, and S(=O)2, other than the N atom bonded to the pyrimidine ring; a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered bridged heterocycle further containing one heteroatom selected from O, S, S=O, and S(=O)2, other than the N atom bonded to the pyrimidine ring; or a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, or 10)-membered spiroheterocycle further containing, other than the N atom attached to the pyrimidine ring, one heteroatom selected from O, S, S=O, and S(=O)2, wherein each ring is fully saturated or has one or more (e.g., 1, 2, or 3) degrees of unsaturation.In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered monocyclic heterocycle containing only N atoms bonded to the pyrimidine ring, a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered bicyclic heterocycle containing only N atoms bonded to the pyrimidine ring, a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered bridged heterocycle containing only N atoms bonded to the pyrimidine ring, a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered fused heterocycle containing only N atoms bonded to the pyrimidine ring, a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered spiro heterocycle containing only N atoms bonded to the pyrimidine ring, a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered heterocycle further containing one heteroatom selected from O in addition to the N atom bonded to the pyrimidine ring. a monocyclic heterocycle; a 5- to 10-membered (e.g., 5, 6, 7, 8, 9, or 10)-membered bicyclic heterocycle further containing one heteroatom selected from O other than the N atom bonded to the pyrimidine ring; a 5- to 10-membered (e.g., 5, 6, 7, 8, 9, or 10)-membered bridged heterocycle further containing one heteroatom selected from O other than the N atom bonded to the pyrimidine ring; a 5- to 10-membered (e.g., 5, 6, 7, 8, 9, or 10)-membered fused heterocycle further containing one heteroatom selected from O other than the N atom bonded to the pyrimidine ring; or a 5- to 10-membered (e.g., 5, 6, 7, 8, 9, or 10)-membered spiroheterocycle further containing one heteroatom selected from O other than the N atom bonded to the pyrimidine ring, wherein each ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10) membered monocyclic heterocycle containing only N atoms bonded to the pyrimidine ring, where the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10) membered bicyclic heterocycle containing only N atoms bonded to the pyrimidine ring, where the ring is fully saturated or has one degree of unsaturation.In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered bridged heterocycle containing only N atoms bonded to the pyrimidine ring, where the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered fused heterocycle containing only N atoms bonded to the pyrimidine ring, where the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered spiro heterocycle containing only N atoms bonded to the pyrimidine ring, where the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered bridged heterocycle containing only the N atom bonded to the pyrimidine ring, wherein the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered monocyclic heterocycle further containing one heteroatom selected from O other than the N atom bonded to the pyrimidine ring, wherein the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered bicyclic heterocycle further containing one heteroatom selected from O other than the N atom bonded to the pyrimidine ring, wherein the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered bridged heterocycle containing, other than the N atom bonded to the pyrimidine ring, one additional heteroatom selected from O, wherein the ring is fully saturated or has one degree of unsaturation. In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10)-membered fused heterocycle containing, other than the N atom bonded to the pyrimidine ring, one additional heteroatom selected from O, wherein the ring is fully saturated or has one degree of unsaturation.In some embodiments, ring A is a 5-10 (e.g., 5, 6, 7, 8, 9, or 10) membered spiroheterocycle further containing one heteroatom selected from O, other than the N atom attached to the pyrimidine ring, wherein the ring is fully saturated or has one degree of unsaturation.

[0041]

[15] . Ring A is [ka] [ka] and Each ring A is optionally, independently, unsubstituted or substituted with m R S1 The compound according to any one of [1] to

[14] , which is substituted with:

[0042]

[16] .R S1 is deuterium, halogen, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 Alkyl group)2, -OH, -OC 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; Optionally, two RS1 together with the carbon atoms bonded to both of these, [ka] or forms a 3- to 6-membered carbon ring, [ka] The 3- to 6-membered carbocyclic rings are independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; Optionally, two adjacent R S1 along with the atoms to which they are bonded, [ka] or form a 3- to 6-membered carbocyclic ring, wherein the 3- to 6-membered carbocyclic ring is independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 The compound according to any one of [1] to

[15] , which is substituted with 1, 2, or 3 substituents selected from alkyl groups.

[0043] In some embodiments, R S1 is -F, -OH, -OCH3, -CN, -CH2F, -CF3, -CH2OCH3, -CH2CN, -CHF2, -CD3, -NH2, or -CH3, or The Two R's S1 together with the carbon atoms bonded to both of these, [ka] or forming a cyclopropyl ring, or Two adjacent R S1 together with the atoms to which they are attached form a cyclopropyl ring.

[0044] In some embodiments, R S1 -F, -CH3, -OH, -OCH3, -CHF2, -CH2OCH3, [ka] -Cl, -CH2CH3, -D, [ka] -CN, [ka] -CHF, -CHCN, [ka] or -CHOH, or The Two R's S1 together with the carbon atoms bonded to both of these, [ka] , a cyclopropyl ring, [ka] or Two adjacent R S1 along with the atoms to which they are bonded, [ka] Form.

[0045] In some embodiments, [ka] teeth, [ka] [ka] [ka] [ka] [ka] [ka] is.

[0046] In some embodiments, [ka] teeth, [ka] [ka] [ka] [ka] and where R S1a , R S1b , or R S1c The definition of R S1 is the same as

[0047] In some embodiments, R S1a is deuterium, halogen, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 1-6 Alkyl groups, halogenated C1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 Alkyl group)2, -OH, -OC 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 In some embodiments, R is substituted with 1, 2, or 3 substituents selected from alkyl groups. S1a is -F, -OH, -OCH3, -CN, -CH2F, -CF3, -CH2OCH3, -CH2CN, -CHF2, -CD3, -NH2, or -CH3.

[0048] In some embodiments, R S1b is deuterium, halogen, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 Alkyl group)2, -OH, -OC 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 In some embodiments, R is substituted with 1, 2, or 3 substituents selected from alkyl groups. S1b is -F, -OH, -OCH3, -CN, -CH2F, -CF3, -CH2OCH3, -CH2CN, -CHF2, -CD3, -NH2, or -CH3.

[0049] In some embodiments, R S1c is deuterium, halogen, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 Alkyl group)2, -OH, -OC 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 In some embodiments, R is substituted with 1, 2, or 3 substituents selected from alkyl groups. S1c is -F, -OH, -OCH3, -CN, -CH2F, -CF3, -CH2OCH3, -CH2CN, -CHF2, -CD3, -NH2, or -CH3.

[0050] In some embodiments, [ka] teeth, [ka] and R S12a is deuterium, halogen, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 Alkyl group)2, -OH, -OC 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 In some embodiments, R is substituted with 1, 2, or 3 substituents selected from alkyl groups. S1a is -F, -OH, -OCH3, -CN, -CH2F, -CF3, -CH2OCH3, -CH2CN, -CHF2, -CD3, -NH2, or -CH3.

[0051] R S12b is deuterium, halogen, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 Alkyl group)2, -OH, -OC 1-6an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 The alkynyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, or halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 In some embodiments, R is substituted with 1, 2, or 3 substituents selected from alkyl groups. S12b is -F, -OH, -OCH3, -CN, -CH2F, -CF3, -CH2OCH3, -CH2CN, -CHF2, -CD3, -NH2, or -CH3.

[0052] In some embodiments, R S12a is -NH(C 1-6 alkyl group) or -N(C 1-6 alkyl group)2, and R S12b is a halogen, -C 1-6 It is an alkyl group, -CN, or a 3- to 6-membered cycloalkyl group.

[0053] In some embodiments, R S12a is -NH(methyl group) or -N(methyl group)2, and R S12b is -F, -Cl, a methyl group, -CN, or a 3-membered cycloalkyl group.

[0054] In some embodiments, [ka] teeth, [ka] [ka] [ka] [ka] [ka] [ka] is.

[0055] In some embodiments, [ka] teeth, [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] is.

[0056] In some embodiments, [ka] teeth, [ka] [ka] is.

[0057] In some embodiments, [ka] teeth, [ka] is.

[0058] In some embodiments, [ka] teeth, [ka] [ka] is.

[0059] In some embodiments, [ka] teeth, [ka] is.

[0060]

[17] The compound according to any one of [1] to

[16] , wherein the compound is one of the formulae in Table A below.

[0061] Table A [ka]

[0062] [ka]

[0063] [ka]

[0064] [ka]

[0065] [ka]

[0066] [ka]

[0067] [ka]

[0068] [ka]

[0069] [ka]

[0070] [ka]

[0071] [ka]

[0072]

[18] The compound according to any one of [1] to

[17] , wherein the compound is one of the formulae in Table B.

[0073] Table B [ka]

[0074] [ka]

[0075] [ka]

[0076] [ka]

[0077] [ka]

[0078] [ka]

[0079] [ka]

[0080] [ka]

[0081] [ka]

[0082] [ka]

[0083] [ka]

[0084] [ka]

[0085] [ka]

[0086] [ka]

[0087] [ka]

[0088]

[19] The compound according to any one of [1] to

[18] , wherein Y1 is O.

[0089]

[20] .R 38 and R 39 and each independently represent hydrogen or deuterium.

[0090]

[21] The compound according to any one of [1] to

[20] , wherein n5 is 1.

[0091]

[22] The compound according to any one of [1] to

[21] , wherein ring I is a 4- to 6-membered cycloalkyl ring.

[0092]

[23] The compound according to any one of [1] to

[22] , wherein ring J is a 4- to 6-membered heterocycle containing 1 or 2 heteroatoms selected from N, O, and S.

[0093] [twenty four]. [ka] teeth, [ka] and where R S381 is hydrogen or R S38 and m 81

[0023] The compound according to any one of [1] to

[23] , wherein is 0, 1, 2, 3, 4, 5, 6, 7, or 8.

[0094]

[25] .R S381 is hydrogen, deuterium, -C 1-6 an alkyl group or a 3- to 6-membered cycloalkyl group, 1-6 The alkyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 The compound according to any one of [1] to

[24] , which is substituted with 1, 2, or 3 substituents selected from alkyl groups.

[0095]

[26] .R S381 is hydrogen, deuterium, —CH 3 , —CH 2 CH 3 , or a cyclopropyl group.

[0096]

[27] .m 81The compound according to any one of [1] to

[26] , wherein is 0.

[0097]

[28] The compound according to any one of [1] to

[27] , wherein m9 is 0, 1, or 2.

[0098]

[29] The compound according to any one of [1] to

[28] , wherein m9 is 0.

[0099]

[30] The compound according to any one of [1] to

[29] , wherein m9 is 1.

[0100]

[31] . [ka] teeth, [ka] [ka] and where R S394 is hydrogen or R S391 The compound according to any one of [1] to

[30] , wherein

[0101]

[32] .R S39 is a halogen, Preferably, R S39 The compound according to any one of [1] to

[31] , wherein is —F.

[0102]

[33] .R S391 is hydrogen, deuterium, halogen, or -C 1-6 is an alkyl group, Here, the above-mentioned -C 1-6 The alkyl groups are independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; Preferably, R S391 The compound according to any one of [1] to

[32] , wherein is hydrogen, deuterium, -F, or -CH3.

[0103]

[34] . [ka] teeth, [ka] [ka] The compound according to any one of [1] to

[33] , wherein

[0104]

[35] . [ka] teeth, [ka] [ka] The compound according to any one of [1] to

[34] , wherein

[0105]

[36] The compound according to any one of [1] to

[21] , wherein ring B is a 4- to 6-membered heterocycle containing the fused N atom.

[0106]

[37] . The compound according to any one of [1] to

[21] and

[36] , wherein ring C is a 4- to 6-membered heterocycle containing the fused N atom.

[0107]

[38] . [ka] teeth, [ka] The compound according to any one of [1] to

[21] and

[36] to

[37] , wherein

[0108]

[39] . The compound according to any one of [1] to

[21] and

[36] to

[38] , wherein m3 is 0, 1, 2, 3, or 4.

[0109]

[40] .R S31 is deuterium or -F, Optionally, two R S31 together with the carbon atoms bonded to both of these, [ka] or a cyclopropyl group, [ka] or the cyclopropyl group is independently unsubstituted or contains 1, 2, or 3 R S311 or Optionally, two adjacent R S31 together with the carbon atom to which each is attached, form a 5- to 10-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N and O, a benzene ring, or a 5- to 10-membered heteroaromatic ring containing 1 or 2 heteroatoms selected from N, O, and S, wherein each ring is independently unsubstituted or contains 1, 2, or 3 R S312 The compound according to any one of [1] to

[21] and

[31] to

[39] , wherein the compound is substituted with

[0110]

[41] . [ka] teeth, [ka] [ka] is selected from where: Ring G is a 5- to 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N and O, a benzene ring, or a 5- to 6-membered heteroaromatic ring containing 1, 2, or 3 heteroatoms selected from N, O, and S; Ring H is a 5- to 10-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N and O, a benzene ring, or a 5- to 10-membered heteroaromatic ring containing 1 or 2 heteroatoms selected from N, O, and S; R S36 The definition of R S31 is the same as R S314 is hydrogen or R S311 and m 31 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, m 32 is 0, 1, 2, 3, 4, 5, 6, 7, or 8, m 33 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, m 34 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, m5 is 0, 1, 2, 3, 4, 5, or 6, The compound according to any one of [1] to

[21] and

[36] to

[40] , wherein m6 is 0, 1, 2, 3, 4, 5, or 6.

[0111]

[42] . [ka] teeth, [ka] [ka] and where: m 31 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, m 32 is 0, 1, 2, 3, 4, 5, 6, 7, or 8, m 33 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, m 34 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, m5 is 0, 1, 2, 3, 4, 5, or 6, The compound according to any one of [1] to

[21] and

[36] to

[41] , wherein m6 is 0, 1, 2, 3, 4, 5, or 6.

[0112]

[43] .R S311 are independently deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -OH, -OC 1-6 Alkyl groups, -CN, -NH2, -NH(C 1-6 alkyl group), or -N(C 1-6 alkyl group)2, wherein the above-mentioned -C 1-6 The alkyl groups are independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; R S312 are independently deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -OH, -OC 1-6 Alkyl groups, -CN, -NH2, -NH(C 1-6 alkyl group), or -N(C1-6 alkyl group)2, wherein the above-mentioned -C 1-6 The alkyl groups are independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 substituted with 1, 2, or 3 substituents selected from alkyl groups; R S314 are independently hydrogen, deuterium, halogen, or -C 1-6 alkyl group, wherein the —C 1-6 The alkyl groups are independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl groups)2, -OH, and -OC 1-6 The compound according to any one of [1] to

[21] and

[36] to

[42] , which is substituted with 1, 2, or 3 substituents selected from alkyl groups.

[0113]

[44] .R S311 are independently deuterium, -F, or -OCH3; R S312 are independently deuterium, -F, -OCH3, or -CH2OCH3; R S314 are independently hydrogen, deuterium, -F, -CH3, -CH2OCH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, or -CH2CH(CH3)2. The compound according to any one of [1] to

[21] and

[36] to

[43] .

[0114]

[45] .R S36 The compound according to any one of [1] to

[21] and

[36] to

[44] , wherein is deuterium or —F.

[0115]

[46] .m 31 is either 0 or 1, m 32 is either 0 or 1, m 33 is either 0 or 1, m 34 is either 0 or 1, m5 is 0 or 1, The compound according to any one of [1] to

[21] and

[36] to

[45] , wherein m6 is 0 or 1.

[0116]

[47] . [ka] teeth, [ka] The compound according to any one of [1] to

[21] and

[36] to

[46] , wherein

[0117]

[48] . [ka] teeth, [ka] [ka] The compound according to any one of [1] to

[21] and

[36] to

[47] , wherein

[0118]

[49] .R 310 and R 311 are each independently hydrogen or deuterium.

[0119]

[50] The compound according to any one of [1] to

[21] and

[49] , wherein n6 is 1 or 2.

[0120]

[51] . The compound according to any one of [1] to

[21] ,

[49] to

[50] , wherein ring K is a 4- to 10-membered heterocycle containing 1 or 2 heteroatoms selected from N and O.

[0121]

[52] . [ka] teeth, [ka] and Here, the ring L is a 4- to 6-membered heterocycle, optionally further containing 1 or 2 heteroatoms selected from N and O. The compound according to any one of [1] to

[21] and

[49] to

[51] .

[0122]

[53] . [ka] teeth, [ka] The compound according to any one of [1] to

[21] and

[49] to

[52] , wherein

[0123]

[54] .R S315 are independently deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -OH, -OC 1-6 Alkyl groups, -CN, -NH2, -NH(C 1-6 alkyl group), or -N(C 1-6 alkyl group)2, wherein the above-mentioned -C 1-6 The alkyl groups are independently unsubstituted or substituted with deuterium, halogen, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy groups, -CN, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6alkyl groups)2, -OH, and -OC 1-6 The compound according to any one of [1] to

[21] and

[49] to

[53] , which is substituted with 1, 2 or 3 substituents selected from alkyl groups.

[0124]

[55] .R S315 are independently -F or -CH3.

[0125]

[56] .m 10 The compound according to any one of [1] to

[21] and

[49] to

[55] , wherein is 0, 1, 2, or 3.

[0126]

[57] . [ka] teeth, [ka] The compound according to any one of [1] to

[21] and

[49] to

[56] , wherein

[0127]

[58] . [ka] teeth, [ka] [ka] The compound according to any one of [1] to

[21] and

[49] to

[57] , wherein

[0128]

[59] . [ka] teeth, [ka] [ka] [ka] [ka] [ka] [ka] [ka] The compound according to any one of [1] to

[21] , wherein

[0129] In some embodiments, [ka] teeth, [ka] is.

[0130] In some embodiments, [ka] teeth, [ka] [ka] is.

[0131] In some embodiments, [ka] teeth, [ka] [ka] is.

[0132]

[60] R4 is a phenyl group, a pyridyl group, a naphthyl group, a quinolyl group, an isoquinolyl group, an indazolyl group, a benzothienyl group, or a benzothiazolyl group, wherein the phenyl group, the pyridyl group, the naphthyl group, the quinolyl group, the isoquinolyl group, the indazolyl group, the benzothienyl group, or the benzothiazolyl group is unsubstituted or has 1, 2, 3, 4, 5, or 6 R S4 The compound according to any one of [1] to

[59] , which is substituted with

[0133]

[61] .R4 is [ka] and m7 is 0, 1, 2, or 3, R S4a is -OH or -NH2, R S4b is hydrogen, deuterium, or a halogen, R S4c is hydrogen, deuterium, -C 1-3 Alkyl group, -C 2-3 Alkenyl group, or -C 2-3 is an alkynyl group, R S4d is hydrogen, deuterium, or a halogen, R S4e is hydrogen, deuterium, halogen, -C 1-3 Alkyl group or halogenated C 1-3 is an alkyl group, R S4f is -OH or -NH2, R S4g is hydrogen, deuterium, halogen, -C 1-3 Alkyl group or halogenated C 1-3 is an alkyl group, R S4h is hydrogen, deuterium, halogen, -C 1-3Alkyl group or halogenated C 1-3 is an alkyl group, R S4i is hydrogen, deuterium, halogen, -C 1-3 Alkyl group or halogenated C 1-3 is an alkyl group, R S4j are hydrogen, deuterium, halogens, -CN, -C 1-3 Alkyl groups, halogenated C 1-3 Alkyl group, or -O halogenated C 1-3 is an alkyl group, R S4k are hydrogen, deuterium, halogens, -CN, -C 1-3 Alkyl groups, halogenated C 1-3 Alkyl group, or -O halogenated C 1-3 is an alkyl group, R S4l are hydrogen, deuterium, halogens, -CN, -C 1-3 Alkyl groups, halogenated C 1-3 Alkyl group, or -O halogenated C 1-3 is an alkyl group, R S4m are hydrogen, deuterium, halogens, -CN, -C 1-3 Alkyl groups, halogenated C 1-3 Alkyl group, or -O halogenated C 1-3 is an alkyl group, R S4n is hydrogen, deuterium, halogen, -C 1-3 Alkyl group or halogenated C 1-3 is an alkyl group, R S4o is hydrogen, deuterium, halogen, -C 1-3 Alkyl group or halogenated C 1-3 is an alkyl group, R S4p is hydrogen, deuterium, halogen, -C 1-3 Alkyl group or halogenated C 1-3 The compound according to any one of [1] to

[60] , which is an alkyl group.

[0134]

[62] .m7 is 0, RS4a is -OH or -NH2, R S4b is -F, R S4c is an ethyl group, a vinyl group, or an ethynyl group, R S4d is hydrogen or -F, R S4e is -F, R S4f is -NH2, R S4g is hydrogen, -F, or a methyl group, R S4h is hydrogen, -F, or a methyl group, R S4i is -I or -CF3, R S4j is -CN, R S4k is hydrogen, R S4l is a methyl group, R S4m is -CF3, -OCF2Cl, -OCF3, or -CF2H, R S4n is hydrogen, -F, or a methyl group, R S4o is hydrogen, -F, or a methyl group, R S4p is hydrogen, —F, or a methyl group.

[0135]

[63] .R4 is [ka] [ka] The compound according to any one of [1] to

[62] , wherein In some embodiments, R4 is [ka] is.

[0136] In some embodiments, R4 is [ka] [ka] is.

[0137] In some embodiments, R4 is [ka] is.

[0138]

[64] The compound according to any one of [1] to

[63] , wherein R5 is halogen.

[0139]

[65] The compound according to any one of [1] to

[64] , wherein R5 is -F.

[0140] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] is.

[0141] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] is.

[0142] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] and R4 is [ka] and [ka] teeth, [ka] is.

[0143] In some embodiments, the compound has the formula: [ka] R5 is -F, -Cl, -CH3, or -OCH3; R S1 is -H, -CH3, or -CD3, -Y1-R3 is [ka] [ka] [ka] and R4 is [ka] [ka] is.

[0144] In some embodiments, the compound has the formula: [ka] -Y1-R3 is [ka] and R S1 teeth, [ka] and R4 is [ka] is.

[0145] In some embodiments, the compound has the formula: [ka] where: R4 is [ka] and -Y1-R3 is [ka] and R7 is [ka] and The R8 is [ka] is.

[0146] In some embodiments, the compound has the formula: [ka] where: R5 is -F, -Cl, -CH3, or -OCH3; R S1 is -H, [ka] or -CD3, -Y1-R3 is [ka] [ka] and R4 is [ka] [ka] is.

[0147] In some embodiments, the compound has the formula: [ka] where: -Y1-R3 is [ka] and R S1 teeth, [ka] and R4 is [ka] is.

[0148] In some embodiments, the compound has the formula: [ka] R5 is -F, -Cl, or -CH3; R S1 teeth, [ka] and R1 is [ka] and -Y1-R3 is [ka] and R4 is [ka] is.

[0149] In some embodiments, the compound has the formula: [ka] R4 is [ka] and -Y1-R3 is [ka] and R S1 teeth, [ka] and R1 is [ka] is.

[0150] In some embodiments, the compound has the formula: [ka] where: R5 is [ka] and R S1 teeth, [ka] and R1 is [ka] and -Y1-R3 is [ka] and R4 is [ka] is.

[0151] In some embodiments, the compound has the formula: [ka] R5 is [ka] and R X13 teeth, [ka] and R S2 teeth, [ka] and R S1 teeth, [ka] and -Y1-R3 is [ka] [ka] [ka] and R4 is [ka] [ka] is.

[0152] In some embodiments, the compound has the formula: [ka] -Y1-R3 is [ka] and R4 is [ka] and R7 is [ka] and The R8 is [ka] is.

[0153] In some embodiments, the compound has the formula: [ka] R5 is [ka] and R S1 teeth, [ka] and R1 is [ka] and -Y1-R3 is [ka] and R4 is [ka] is.

[0154] In some embodiments, the compound has the formula: [ka] where: R5 is -F, -Cl, -CH3, or -OCH3; R X13is -CH3 or -CD3, R S2 is -H, -CH3, or -CD3, R S1 is -H, -CH3, or -CD3, -Y1-R3 is [ka] [ka] [ka] and R4 is [ka] [ka] is.

[0155] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] is.

[0156] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] is.

[0157] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] and R4 is [ka] and [ka] teeth, [ka] is.

[0158] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] is.

[0159] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] is.

[0160] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] and R4 is [ka] and [ka] teeth, [ka] is.

[0161] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] and R4 is [ka] and [ka] teeth, [ka] is.

[0162] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0163] In some embodiments, the compound is [ka] and where: R S1a teeth, [ka] and R S1c teeth, [ka] and [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0164] In some embodiments, the compound is [ka] and where: R S1b teeth, [ka] and [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0165] In some embodiments, the compound is [ka] and where: R S1a teeth, [ka] and R S1c teeth, [ka] and [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0166] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0167] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0168] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] and [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0169] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] and R4 is [ka] is.

[0170] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] and R4 is [ka] is.

[0171] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] [ka] [ka] [ka] [ka] [ka] and R4 is [ka] is.

[0172] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] [ka] [ka] [ka] [ka] and R4 is [ka] is.

[0173] In some embodiments, the compound is [ka] and where: R1 is [ka] and [ka] teeth, [ka] and R4 is [ka] is.

[0174] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] and [ka] teeth, [ka] and R4 is [ka] is.

[0175] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] and [ka] teeth, [ka] and R4 is [ka] is.

[0176] In some embodiments, the compound is [ka] and where: R1 is [ka] and [ka] teeth, [ka] and R4 is [ka] is.

[0177] In some embodiments, the compound is [ka] and where: [ka] teeth, [ka] is.

[0178]

[66] The compound according to any one of [1] to

[65] , wherein the compound is any one of the compounds in Table C.

[0179] Table C [ka]

[0180] [ka]

[0181] [ka]

[0182] [ka]

[0183]

change

[0184]

change

[0185]

change

[0186]

change

[0187]

change

[0188]

change

[0189]

change

[0190]

change

[0191]

change

[0192]

change

[0193]

change

[0194] [ka]

[0195] [ka]

[0196] [ka]

[0197] [ka]

[0198] [ka]

[0199]

[67] . A pharmaceutical composition comprising a therapeutically effective amount of a compound represented by formula (I) according to any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, and a pharmaceutically acceptable excipient.

[0200]

[68] . A method for treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by formula (I) as set forth in any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition as set forth in

[67] .

[0201]

[69] A method for treating cancer in a subject in need thereof, comprising: (a) determining whether the cancer is associated with K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-Ras G12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutations, and / or K-Ras wild-type amplification; and (b) Where relevant, a method for treating cancer in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of formula (I) as set forth in any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition as set forth in

[67] .

[0202]

[70] . A compound of formula (I) according to any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition according to

[67] , for use in therapy.

[0203]

[71] . A compound represented by formula (I) according to any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition according to

[67] , for use as a pharmaceutical.

[0204]

[72] . A compound of formula (I) according to any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition according to

[67] , for use in a method for treating cancer.

[0205]

[73] . Use of a compound represented by formula (I) according to any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition according to

[67] , in the treatment of cancer.

[0206]

[74] . Use of a compound represented by formula (I) according to any one of [1] to

[66] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition according to

[67] , in the preparation of a medicament for treating cancer.

[0207]

[75] . The cancer is selected from pancreatic cancer, colorectal cancer, lung cancer (e.g., non-small cell lung cancer), breast cancer, colon cancer, gastric cancer, endometrial cancer, esophageal cancer, or gastroesophageal junction cancer. A method for treating cancer according to

[68] , use in the method for treating cancer according to

[72] , use in the treatment of cancer according to

[73] , or use in the preparation of a medicament for treating cancer according to

[74] .

[0208]

[76] . The cancer is associated with at least one of K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-Ras G12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutations, and / or K-Ras wild-type amplification. A method for treating cancer according to

[68] or

[75] , use in a method for treating cancer according to

[72] or

[75] , use in the treatment of cancer according to

[73] or

[75] , or use in the preparation of a medicament for treating cancer according to

[74] or

[75] .

[0209] The present invention provides the following: [B-1]. A compound represented by formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, [ka] where: R3 is -C 1-6 an alkylene group, optionally containing deuterium, halogen, -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, halogenated C 2-6 Alkenyl group, -C 2-6 Alkynyl group, halogenated C 2-6 Alkynyl group, -N(R A )2, -OR A , -SR A , -S(=O)R B , -S(=O)2R B , -C(=O)R B , -C(=O)OR B , -C(=O)N(R B )2, -S(=O)OR B , -S(=O)N(R B )2, -S(=O)2OR B , -S(=O)2N(R B )2, -P(=O)(R B ) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Here, the above-mentioned -C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C 1-6 Alkyl groups, halogenated C 1-6 Alkyl groups, halogenated C 1-6 Alkoxy group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, -CN, -NO2, -N3, oxo, -N(R C )2, -OR C , -SR C , -S(=O)R D , -S(=O)2R D , -C(=O)R D , -C(=O)OR C , -OC(=O)R D , -C(=O)N(R C )2, -NR C C(=O)R D , -OC(=O)OR C , -NR C C(=O)OR D , -OC(=O)N(R C )2, -NR C C(=O)N(R C )2, -S(=O)OR C , -OS(=O)R D , -S(=O)N(R C )2, -NR C S(=O)R D , -S(=O)2OR C , -OS(=O)2R D , -S(=O)2N(R C )2, -NR C S(=O)2R D , -OS(=O)2OR C , -NR C S(=O)2OR C , -OS(=O)2NR C , -NR C S(=O)2N(R C )2, -P(R C )2, -P(=O)(R D) 2, substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Ring A, R S1 , m1, R S2 , m2, n1, X1, X2, R4, R5, Y1, R A , R B , R C , R D The definition of is the same as that of any one of [1] to

[66] , a compound, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof.

[0210] [B-2].R3 is -N(R A )2 substituted with -C 1-6 is an alkylene group, R A is hydrogen or -C 1-3 The compound according to [B-1], which is an alkyl group.

[0211] [B-3] R3 is -C substituted with -N(CH3)2 1-6 The compound according to [B-2], which is an alkylene group.

[0212] [C-1]. [ka] An intermediate having the structure L1 is a leaving group, L2 is a leaving group, Ring A, R S1 , m1, R S2 An intermediate in which the definitions of m2, n1, X1, X2, R5, Y1, and R3 are the same as those in any one of [1] to

[66] and [B-1] to [B-3].

[0213] [C-2]. An intermediate according to [C-1], wherein L1 is selected from -Cl, -Br, -S(=O)CH3 or -S(=O)2CH3.

[0214] [C-3]. An intermediate according to [C-1] or [C-2], wherein L2 is selected from -Cl or -Br.

[0215] [C-4].-Y1-R3 is [ka] The intermediate according to any one of [C-1] to [C-3], wherein

[0216] [C-5] The intermediate according to any one of [C-1] to [C-4], which is any one of the intermediates in Table D.

[0217] Table D [ka]

[0218] [ka]

[0219] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents, patent applications, and publications cited herein are incorporated herein by reference.

[0220] Unless otherwise specified, the term "halogen" or "halogenated" as used herein refers to fluorine, chlorine, bromine, or iodine. Preferred halogen groups include -F, -Cl, and -Br.

[0221] Unless otherwise specified, the term "alkyl group" as used herein includes saturated monovalent hydrocarbyl groups having straight or branched chains. For example, -C 1-6 Alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 3-(2-methyl)butyl, 2-pentyl, 2-methylbutyl, neopentyl, n-hexyl, 2-hexyl, and 2-methylpentyl. 1-3 C in alkyl groups 1-3 is defined as a group having 1, 2, or 3 carbon atoms arranged in a linear or branched chain.

[0222] Unless otherwise specified, as used herein, "halogenated alkyl groups" (e.g., -C 1-6 Halogenated alkyl groups, -C 1-4 Halogenated alkyl groups, -C 1-3 Halogenated alkyl group, or halogenated C 1-6 The term alkyl group refers to an alkyl group as defined herein (e.g., —C 1-6 Alkyl group, -C 1-4 Alkyl group, or -C 1-3 It indicates that one or more (e.g., one, two, or three) hydrogen atoms in a methyl group (e.g., alkyl group) are replaced with halogen. Examples include trifluoromethyl, difluoromethyl, and fluoromethyl groups.

[0223] The term "alkylene group" refers to a difunctional group obtained by removal of a hydrogen atom from an alkyl group, as defined above. Examples include a methylene group (i.e., -CH-), an ethylene group (i.e., -CH-CH- or -CH(CH)-), and a propylene group (i.e., -CH-CH-CH-, -CH(-CH-CH)-, or -CH-CH(CH)-).

[0224] The term "alkenyl group" refers to a straight or branched chain hydrocarbyl group having one or more double bonds and generally from 2 to 20 carbon atoms in length. For example, "-C 2-6 An "alkenyl group" is an alkenyl group having 2 to 6 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl, propenyl, butenyl, 2-methyl-2-buten-1-yl, heptenyl, and octenyl groups.

[0225] The term "alkynyl group" refers to a straight or branched chain hydrocarbyl group having one or more triple bonds and generally from 2 to 20 carbon atoms in length. For example, "-C 2-6 An "alkynyl group" is an alkynyl group having 2 to 6 carbon atoms. Representative alkynyl groups include, but are not limited to, for example, ethynyl, 1-propynyl, 1-butynyl, heptynyl, octynyl, and the like.

[0226] The term "alkoxy group" refers to oxygen ethers formed by the alkyl groups defined above.

[0227] Unless otherwise specified, the term "aryl group," as used herein, refers to an unsubstituted or substituted, monocyclic or polycyclic aromatic ring system having carbon ring atoms. Preferred aryl groups are monocyclic or bicyclic 6- to 10-membered aromatic ring systems. Phenyl and naphthyl groups are preferred aryl groups.

[0228] Unless otherwise specified, the term "heterocycle" or "heterocyclyl group," as used herein, refers to an unsubstituted or substituted, monocyclic or polycyclic non-aromatic ring system containing one or more heteroatoms, including monocyclic heterocycles, bicyclic heterocycles, bridged heterocycles, fused heterocycles, or spiro heterocycles. Preferred heteroatoms include N, O, and S, including N-oxides, sulfoxides, and dioxides. Preferably, the ring is 3-10 membered and is fully saturated or has one or more degrees of unsaturation. This definition includes multiple degrees of substitution, preferably 1, 2, or 3. Examples of such heterocyclyl groups include, but are not limited to, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxopiperazinyl, oxopiperidinyl, oxoazepanyl, azanyl, tetrahydrofuranyl, dioxolanyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydrooxazolyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thianyl, morpholine sulfoxide, thiomorpholine sulfone, and oxadiazole groups.

[0229] Unless otherwise specified, the term "heteroaryl group" as used herein refers to an aromatic ring system containing carbon and at least one heteroatom. Heteroaryl groups can be monocyclic or polycyclic, substituted or unsubstituted. Monocyclic heteroaryl groups can have 1 to 4 heteroatoms in the ring, while polycyclic heteroaryl groups can have 1 to 10 heteroatoms. Polycyclic heteroaryl rings can have fused rings, spiro rings, or bridged rings; for example, a bicyclic heteroaryl group is a polycyclic heteroaryl group. Bicyclic heteroaryl rings can have 8 to 12 member atoms. Monocyclic heteroaryl rings can have 5 to 8 member atoms (carbon and heteroatom). Illustrative examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, triazolyl, pyridyl, pyridazinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, benzofuranyl, benzothienyl, benzisoxazolyl, benzoxazolyl, benzopyrazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, adenyl, quinolyl, or isoquinolyl.

[0230] The term "carbocycle" refers to a substituted or unsubstituted monocyclic, bicyclic, bridged, fused, or spirocyclic non-aromatic ring system containing only carbon atoms. Exemplary "cycloalkyl groups" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

[0231] Unless otherwise specified, the term "one or more," as used herein, refers to one or more. In some embodiments, "one or more" refers to one, two, three, four, five, or six. In some embodiments, "one or more" refers to one, two, three, or four. In some embodiments, "one or more" refers to one, two, or three. In some embodiments, "one or more" refers to one or two. In some embodiments, "one or more" refers to one. In some embodiments, "one or more" refers to two. In some embodiments, "one or more" refers to three. In some embodiments, "one or more" refers to four. In some embodiments, "one or more" refers to five. In some embodiments, "one or more" refers to six.

[0232] Unless otherwise specified, the term "substituted" used herein refers to the substitution of a hydrogen atom on a carbon atom or a hydrogen atom on a nitrogen atom with a substituent.In the present invention, when one or more substituents are substituted on a ring, each substituent can be independently substituted on each ring atom of the ring, and the ring atom includes, but is not limited to, a ring carbon atom or a ring nitrogen atom.In addition, when the ring is a polycyclic ring such as a fused ring, a bridged ring, or a spiro ring, each substituent can be independently substituted on each ring atom of the polycyclic ring.

[0233] The term "oxo" refers to the oxygen atom, together with the carbon atom to which it is attached. [ka] It refers to forming a group.

[0234] It is intended that the definition of any substituent or variable at a particular location in a molecule be independent of its definitions elsewhere in that molecule. It is to be understood that substituents and substitution patterns on the compounds of the invention can be selected by those skilled in the art to provide chemically stable compounds.

[0235] As used herein, the term "composition" is intended to include a product containing the specified ingredients in the specified amounts, as well as any product resulting directly or indirectly from the combination of the specified ingredients in the specified amounts. Accordingly, pharmaceutical compositions containing the compounds of the present invention as active ingredients are part of the present invention. Also, some crystalline forms of the compounds may exist as polymorphs, and are therefore intended to be included in the present invention. Furthermore, some compounds may form solvates with water (i.e., hydrates) or common organic solvents, and such solvates are also intended to be included within the scope of the present invention.

[0236] The term "pharmaceutically acceptable salt" refers to a salt prepared from a pharmaceutically acceptable non-toxic base or acid. When a compound of the present invention is acidic, its corresponding salt can be easily prepared from a pharmaceutically acceptable non-toxic base, including inorganic bases and organic bases. When a compound of the present invention is basic, its corresponding salt can be easily prepared from a pharmaceutically acceptable non-toxic acid, including inorganic acids and organic acids. Because the compounds of the present invention are intended for pharmaceutical use, they are preferably provided in a substantially pure form, for example, at least 60% pure, more suitably at least 75% pure, and particularly at least 98% pure (% by weight).

[0237] The scope of the present invention includes prodrugs of the compounds of the present invention. Generally, such prodrugs are functional derivatives that can be easily converted into the desired compound in the body. Thus, in the therapeutic methods of the present invention, the term "administration" is intended to include treating the various conditions described with the specifically disclosed compounds or compounds that are not specifically disclosed but can be converted into the specified compound in the body after administration to a subject. General procedures for selecting and preparing suitable prodrug derivatives are described, for example, in "Design of Prodrugs," H. Bundgaard, Elsevier, 1985.

[0238] The present invention includes all stereoisomers of the compounds and their pharmaceutically acceptable salts. It also includes mixtures of stereoisomers and resolved specific stereoisomers. During synthetic procedures to prepare such compounds, or procedures using racemization or epimerization methods known to those skilled in the art, the product of such procedures may be a mixture of stereoisomers. As used herein, the term "stereoisomer" refers to isomers in which atoms or groups in a molecule are bonded in the same order but differ in spatial arrangement, including conformational isomers and configurational isomers. Configurational isomers include geometric isomers and optical isomers, and optical isomers primarily include enantiomers and diastereomers. The present invention includes all possible stereoisomers of the compounds (e.g., their atropisomers). The absolute configuration of the present compounds can be confirmed by common technical methods, such as X-ray single crystal diffraction or cocrystallization with a KRAS mutant protein, or by comparing the pharmacological activity of two isomers with that of a pair of isomers whose absolute configuration has been determined.

[0239] The present invention is intended to include all isotopes of atoms occurring in the compounds of the present invention. Isotopes include atoms having the same atomic number but different mass numbers. By way of general example, isotopes of hydrogen include, but are not limited to, deuterium and tritium. Isotopes of hydrogen include, 1 H (hydrogen), 2 H (deuterium), and 3 H (tritium). They are also commonly referred to as D (deuterium) and T (tritium). As used herein, -CD3 represents a methyl group in which all hydrogen atoms are deuterium. Carbon isotopes include: 13 C and 14 It contains C. The isotopes of oxygen are 16 O. 17 O, or 18 Isotopically labeled compounds of the present invention can generally be prepared by common techniques known to those skilled in the art or by methods analogous to those described herein, using the appropriate isotopically labeled reagent in place of the unlabeled reagent.

[0240] Unless otherwise specified, the term "deuterated molecule" as used herein refers to a compound having the same chemical structure as a reference compound, but in which one or more hydrogen atoms have been replaced with deuterium atoms ("D"). It should be recognized that some variation in natural isotopic abundance may occur in a synthesized compound depending on the source of chemicals used in its synthesis. Despite such variation, the concentration of naturally occurring stable hydrogen isotopes is very small and negligible compared to the degree of stable isotopic substitution in the deuterated derivatives described herein. Thus, unless otherwise specified, when referring to a "deuterated molecule" of a compound herein, at least one hydrogen has been replaced with deuterium in far excess of its natural isotopic abundance (usually about 0.015%).

[0241] Unless otherwise specified, when tautomers exist in the compounds of the present invention, the present invention includes any possible tautomers, pharmaceutically acceptable salts thereof, and mixtures thereof.

[0242] "PROTAC molecule" refers to a compound described herein linked, with or without a linker, to another agent, where the compound functions as a K-Ras protein (including K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-Ras G12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutant proteins, and K-Ras wild-type protein), e.g., the compound is incorporated into a protease-targeting chimera (PROTAC).

[0243] Unless otherwise clear from the context, when a value is expressed as "about" X or "approximately" X, the value indicated for X should be understood to be accurate to ±10%, preferably ±5%, ±2%.

[0244] The term "subject" refers to an animal. In some embodiments, the animal is a mammal. The subject further refers to, for example, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds, etc. In some embodiments, the subject is human. As used herein, a "patient" refers to a human subject. As used herein, a subject is "in need of" treatment if the subject would derive biological, medical, or quality of life benefit from such treatment. In some embodiments, the subject is experiencing and / or exhibiting at least one symptom of a cancer to be treated and / or prevented. In some embodiments, the subject has been identified or diagnosed as suffering from a K-Ras G12A, K-Ras G12C, K-Ras G12D, K-Ras G12R, K-Ras G12S, K-Ras G12V, K-Ras G13D K-Ras Q61H mutation and / or wild-type K-Ras amplification cancer.

[0245] The terms "inhibition," "inhibiting," or "inhibit" refer to the alleviation or suppression of a given condition, symptom, condition, or disease, or a significant decrease in the baseline activity of a biological activity or process.

[0246] In one embodiment, the terms "treat," "treating," or "treatment" of any disease or condition refers to ameliorating the disease or condition (i.e., slowing, arresting, or reducing the progression of the disease or at least one clinical symptom thereof). In another embodiment, "treat," "treating," or "treatment" refers to the alleviation or improvement of at least one physical parameter, including parameters not discernible by the patient. In yet another embodiment, "treat," "treating," or "treatment" refers to physically (e.g., stabilizing discernible symptoms), physiologically (e.g., stabilizing physical parameters), or otherwise modulating the disease, condition, or any of these. In yet another embodiment, "treat," "treating," or "treatment" refers to preventing or delaying the onset, progression, or development of the disease or condition. [Example]

[0247] The following examples are provided to better illustrate the present invention. Unless otherwise specified, all parts and percentages are by weight and all temperatures are in degrees Celsius. The following abbreviations are used in the examples:

[0248] [Table 1]

[0249] [Table 2]

[0250] Preparation of intermediates INT1: [ka] INT2: [ka] INT3: [ka] INT4: [ka] INT5: [ka] INT6: [ka] INT7: [ka] INT8: [ka] INT9: [ka] INT12: [ka] INT14: [ka]

[0251] The intermediates were either purchased or prepared by prior art techniques.

[0252] INT10 [ka]

[0253] To a solution of INT11-6 (8.2 g) in DCM (100 ml) was added DIEA (11.82 g), and trifluoromethanesulfonic anhydride (15.77 g) was added dropwise at 0 °C. The reaction mixture was stirred overnight at RT under a N atmosphere, adjusted to pH 8 with NaHCO solution, and extracted with DCM. The organic layer was worked up and purified to give INT10-1 (9.24 g).

[0254] A solution of INT10-1 (9.24 g), benzophenone imine (3.34 g), Cs2CO3 (14.87 g), Pd2(dba)3 (0.90 g), and Xantphos (1.7 g) in 1,4-dioxane (100 ml) was stirred at 80 °C under a N2 atmosphere overnight. The solution was extracted with EA. The separated organic layer was worked up and purified to give INT10-2 (5.71 g).

[0255] A solution of INT10-2 (5.71 g), KOAc (2.67 g), bis(pinacolato)diboron (4.24 g), and Pd(dppf)Cl (0.66 g) in toluene (60 ml) was stirred overnight at 120 °C under a N atmosphere. The solution was extracted with EA, and the separated organic layer was worked up and purified to give INT10 (3.02 g).

[0256] INT11 [ka]

[0257] INT11 was prepared by a method similar to the synthesis of INT2 described in WO2021041671.

[0258] INT13 [ka]

[0259] INT13 was prepared by a method similar to that used to synthesize INT10.

[0260] INT15 [ka]

[0261] Under a N2 atmosphere, POCl3 (4 ml) was added to a solution of INT6 (4.03 g) and DIEA (8 ml) in toluene (25 ml), and the resulting mixture was stirred at 80 °C for 2 h and concentrated. The residue was diluted with DCM (40 ml), and DIEA (3 ml) and but-3-en-1-amine hydrochloride (1.65 g) were added. The reaction mixture was stirred at RT for 1 h and diluted with DCM and water. The separated organic layer was concentrated and purified to give INT15-1 (4.61 g). MS: m / z 333 [M+H] + .

[0262] To a solution of INT15-1 (4.61 g) and methylammonium chloride (2.86 g) in DMAc (40 ml) was added DIEA (9.07 g). The mixture was purged with N2 and then stirred at 70 °C for 16 hours. It was diluted with EA and water. The separated organic layer was concentrated and purified to give INT15-2 (3.60 g). MS: m / z 328 [M+H] + .

[0263] To a solution of benzaldehyde (1.00 g) in MeOH (20 ml), piperidine (2.34 g) and 1,1-dimethoxypropan-2-one (4.36 g) were added. The mixture was purged with N2, stirred at RT overnight, diluted with EA, and washed with water. The separated organic layer was concentrated and purified to give INT15-3 (1.0 g). MS: m / z 207 [M+H] + .

[0264] To a solution of INT15-3 (0.31 g) and INT15-2 (0.38 g) in DMSO (5 ml), TsOH·HO (0.30 g) was added. The mixture was purged with N and stirred at 80 °C overnight, cooled to RT, diluted with EA, and washed with water. The separated organic layer was concentrated and purified to give INT15-4 (0.48 g). MS: m / z 470 [M+H] + .

[0265] To a solution of INT15-4 (1.12 g) in toluene (20 ml) was added Grubbs Gen 2nd (0.42 g). The mixture was purged with N2, stirred at 80 °C for 2 h, cooled to RT, and concentrated. The residue was purified to give INT15 (0.28 g). MS: m / z: 366 [M+H] + .

[0266] INT16 [ka]

[0267] INT16-a (70.59 g) and TEA (29.70 g) were cooled to -15°C in a THF (1000 ml) solution. Isobutyl chloroformate (36.31 g) was added to the resulting mixture, which was stirred at the same temperature for 2 hours and then filtered. The filtrate was cooled to 0°C and added dropwise to a solution of NaBH4 (16.71 g) in water (200 ml). The solution was stirred at 0°C for 1 hour. The mixture was quenched with water and extracted with EA. The organic layer was worked up and purified to give INT16-1 (74.35 g, 110.5% yield). MS (ESI, m / z): 282 [M+H] + .

[0268] Sodium hydride (60% in oil, 1.77 g) was added to a solution of 3-chloro-2-(chloromethyl)-1-propene (1.92 g) in DMF (15 ml) at 0 °C under a N atmosphere, and the resulting mixture was stirred at RT for 30 min. A solution of INT16-1 (3.82 g) in anhydrous THF (15 ml) was added to the reaction mixture, which was stirred at RT for 18 h and diluted with EA and water. The separated organic layer was worked up and purified to give INT16-2 (2308 mg). MS: m / z 334 [M+H] + .

[0269] To a solution of INT16-2 (2308 mg) and K2OsO4·2H2O (0.13 g) in THF (25 ml) and water (12 ml) was added NaIO4 (6.06 g). The mixture was stirred at RT for 18 h and diluted with EA and water. The separated organic layer was worked up and purified to give INT16-3 (2165 mg). MS: m / z 336 [M+H] + .

[0270] To a solution of INT16-3 (2165 mg) in THF (15 ml) was added NaBH (495 mg) at -20 °C under a N atmosphere. The resulting mixture was stirred for 1 h and diluted with EA and saturated NH Cl. The separated organic layer was worked up and purified to give INT16-4 (2.02 g). MS: m / z 338 [M+1] + .

[0271] To a solution of INT16-4 (2.02 g) in DCM (15 ml) was added BAST (495 mg) at -20 °C under N2 atmosphere, and the resulting mixture was stirred at RT for 18 h and then diluted with DCM and saturated NaHCO3. The separated organic layer was concentrated and purified to give INT16 (0.98 g). MS: m / z: 340 [M+1] + .

[0272] INT17 [ka]

[0273] To a solution of INT15 (2.02 g) in MeOH (200 ml) and DCM (300 ml) at 0 °C, NaBH4 (0.64 g) and CeCl3·7H2O (6.12 g) were added, and the resulting mixture was stirred for 4 h. The mixture was quenched with H2O and extracted with EA. The organic layer was worked up to give INT17 (2.02 g, crude product). MS: m / z: 479 [M+1] + .

[0274] Example 1 [ka]

[0275] CP1-5 were prepared by a method similar to the procedure described in WO2023046135.

[0276] To a solution of CP1-5 (296 mg) in CH3CN (15 ml) was added HCl (4 M in 1,4-dioxane, 5 ml). The reaction mixture was stirred at RT for 1 h and concentrated. The residue was dissolved in EA and washed with aq. NaHCO3 (sat.). The organic layer was dried and concentrated to give CP1-6 (316 mg). MS (ESI, m / z): 774 [M+H] + .

[0277] A solution of CP1-6 (292 mg) and pyridine (360 mg) in DCM (6 ml) was cooled to -20 °C, trifluoromethanesulfonic anhydride (573 mg) was added dropwise, and the mixture was allowed to warm to RT. The reaction mixture was stirred at RT for 2 h and then concentrated. The residue was dissolved in EA and washed with water. The organic layer was dried, concentrated, and purified by prep-TLC (DCM:MeOH = 30:1, v / v) to give CP1-7 (251 mg). MS (ESI, m / z): 906 [M+H] + .

[0278] A solution of CP1-7 (51 mg), benzophenone imine (24 mg), Pd(dba) (12 mg), Xantphos (13 mg), and CsCO (55 mg) in toluene (3 mL) was stirred at 100 °C for 16 h under a N atmosphere and washed with EA and water. The organic layer was dried, concentrated, and purified by prep-TLC (Hex:EA = 0:1, v / v) to give CP1-8 (49 mg). MS (ESI, m / z): 937 [M+H] + .

[0279] To a solution of CP1-8 (49 mg) in DCM (3 ml) was added HCl (4 M in 1,4-dioxane, 0.3 ml). The reaction mixture was stirred at RT for 16 h and concentrated. The residue was dissolved in EA and washed with saturated aqueous NaHCO3. The organic layer was dried and concentrated to give CP1-9 (53 mg). MS (ESI, m / z): 773 [M+H] + .

[0280] To a solution of CP1-9 (53 mg) in DMF (3 mL) was added CsF (105 mg). The reaction mixture was stirred at 40 °C for 2 hours and then filtered to collect the filtrate. The filtrate was concentrated and purified by prep-HPLC (Ultimate XB-C18, Phase A: water with 0.05% trifluoroacetic acid, Phase B: CH3CN, gradient: 10% B to 28% B in 25 min, flow rate: 40 mL / min, 228 nm) to obtain compound 1 (CP1, confirmed). MS (ESI, m / z:): 617 [M+H] + .

[0281] Example 2 [ka]

[0282] Compound 2 (CP2, 38.5 mg, TFA salt, confirmed) was synthesized from 2-a by a method similar to that for CP1. MS (ESI, m / z:): 624 [M+H] + .

[0283] Example 3 [ka]

[0284] To a solution of CP2-1 (103 mg) and INT13 (337 mg) in toluene (7.5 mL) and water (1.5 mL) was added Cs2CO3 (147 mg) and cataCXium A Pd G3 (18 mg). The reaction mixture was stirred overnight at 100 °C under a N2 atmosphere, then worked up and purified by prep-TLC to give CP3-1 (65 mg). MS: m / z: 943 [M+H]+ .

[0285] A procedure similar to that for preparing CP1 was used to obtain compound 3 (CP3, 19.5 mg, TFA salt, confirmed) in CP3-1. MS (ESI, m / z:): 623 [M+H] + .

[0286] Example 4 [ka]

[0287] Compound 4 (CP4, confirmed) was synthesized by a method similar to that for CP9.

[0288] Example 5 [ka]

[0289] Compound 5 (CP5, confirmed) was synthesized and purified from 5-a and CP1-3 by a method similar to that for CP3. The resulting product was separated by Prep-HPLC (Ultimate XB-C18, 30 mm x 150 mm, 5 μm, Phase A: water with 0.1% trifluoroacetic acid, Phase B: CH3CN, gradient: 15% B to 35% B in 30 min, flow rate: 40 mL / min, 250 nm) to give compound 5A (CP5A, 2.9 mg, first peak, TFA salt) and compound 5B (CP5B, 3.6 mg, second peak, TFA salt). MS (ESI, m / z: 629 [M+H]). + .

[0290] Example 6 [ka]

[0291] To a solution of CP1 (30 mg) in MeOH (10 mL) was added Pd / C (75 mg, 10% content). The mixture was stirred at RT under H2 atmosphere for 1.5 hours, filtered, and the filtrate was concentrated and purified by Prep-HPLC (Agela Durashell C18, 30 mm x 250 mm, 10 μm, A: 0.1% TFA in water, B: CH3CN, gradient: 10% B to 29% B in 31 minutes, flow rate 40 mL / min, 230 nm) to give compound 6A (CP6A, 4.7 mg, TFA salt, confirmed). LCMS: m / z: 621 [M+H]. + and compound 6B (CP6B, 10 mg, TFA salt, confirmed). LCMS: m / z: 619 [M+H] + .

[0292] Example 7 [ka]

[0293] Compound 7 (CP7, 25.9 mg, TFA salt, confirmed) was synthesized from 7-a and CP1-3 in a similar manner to CP1. LCMS: m / z: 611 [M+H] + .

[0294] Example 8 [ka]

[0295] Compound 8 (CP8, confirmed) was synthesized using INT11 and CP1-4 in a similar manner to CP1. LCMS: m / z: 635 [M+H] + .

[0296] Example 9 [ka]

[0297] To a solution of 9-a (2.49 g) in THF (10 ml) was added NaH (60% in oil, 1.15 g) at 0° C. After stirring for 0.75 h, DMAP (63 mg), TBAI (394 mg) and bromoacetaldehyde dimethyl acetal (4.35 g) were added to the mixture. The reaction mixture was stirred at 70° C. for 23 h. The reaction mixture was quenched with water and extracted with EA. The organic layer was washed with brine, dried, filtered and concentrated. The residue was purified on a silica gel column to give CP9-1 (3.55 g). LCMS: m / z: 343 [M+H] + .

[0298] To a solution of CP9-1 (1.56 g) in MeOH (25 ml), Pd(OH) / C (0.84 g) was added. The reaction mixture was stirred at RT for 5 h under an H atmosphere, filtered, and the filtrate was concentrated to give CP9-2 (0.75 g). MS m / z: 164 [M+H] + .

[0299] To a solution of INT6 (1.27 g) and DIEA (1.76 g) in toluene (15 ml) was added POCl3 (0.8 ml). The reaction mixture was stirred at 80 °C for 1.5 h and concentrated. The resulting residue was dissolved in DCM (10 ml), and CP9-2 (0.75 g) and DIEA (2 ml) were added at 0 °C. The reaction mixture was stirred at RT for 1.5 h, then diluted with water and extracted with EA. The collected organic layer was washed with brine, dried, concentrated, and purified on a silica gel column to give CP9-3 (1.38 g). MS: m / z: 425 [M+H] + .

[0300] A mixture of CP9-3 (0.31 g), methylamine hydrochloride (216 mg), CsCO (1254 mg), and DMAc (4 ml) in an 8 ml sealed bottle was stirred at 100 °C for 17 h. The reaction mixture was diluted with water and extracted with EA. The organic layer was washed with brine, dried, concentrated, and purified by prep-TLC to give CP9-4 (226 mg). MS: m / z: 420 [M+H] + .

[0301] To a solution of CP9-4 (200 mg) in 1,4-dioxane (4 ml), TsOH·HO (97 mg) was added. The solution was stirred at 100 °C under N atmosphere for 24 hours, then diluted with water and extracted with EA. The collected organic layer was washed with brine, dried, concentrated, and purified by prep-TLC to give CP9-5 (52 mg). MS: m / z 356 [M+H] + .

[0302] To a solution of CP9-5 (52 mg) in DCM (10 ml) was added m-CPBA (50 mg) at RT. The mixture was stirred for 0.75 h, then quenched with aq. NaSO and extracted with DCM. The mixture was washed with sat. aq. NaHCO, dried, and concentrated to give CP9-6 (58 mg). MS: m / z: 372 [M+H] + .

[0303] To a solution of INT14 (42 mg) in THF (3 ml) was added t-BuONa (30 mg). After stirring for 10 min, a solution of CP9-6 (58 mg) in THF (1 ml) was added. The mixture was stirred at RT for 0.5 h, quenched with water, and extracted with EA. The organic layer was washed with brine, dried, concentrated, and purified by prep-TLC to give CP9-7 (53 mg). MS: m / z: 467 [M+H] + .

[0304] To a solution of CP9-7 (53 mg) and INT2 (77 mg) in toluene (6 ml) and water (1.5 ml) was added cataCXium A Pd G3 (23 mg) and Cs2CO3 (91 mg). The reaction mixture was stirred at 100 °C for 18 hours under a N2 atmosphere. The mixture was diluted with water and extracted with EA. The collected organic layer was washed with aq. NaCl, dried, concentrated, and purified by prep-TLC to give CP9-8 (43 mg). MS: m / z: 817 [M+H] + .

[0305] A solution of CP9-8 (43 mg), HCl (4 M in dioxane, 1 ml) in DCM (3 mL) was stirred at RT for 1 h. The solution was concentrated, diluted with sat. NaHCO3 solution, and extracted with EA. The collected organic layer was washed with brine, dried, and concentrated to give CP9-9 (51 mg, crude product). MS: m / z: 773 [M+H] + .

[0306] A mixture of CP9-9 (51 mg, crude product) and CsF (0.30 g) in DMF (5 ml) was stirred at 40 °C for 1.5 hours. The mixture was diluted with water and extracted with EA. The organic layer was dried, concentrated, and purified by prep-HPLC (Daisogel-C18, 50 mm × 250 mm, 10 μm, A: water with 0.05% trifluoroacetic acid, B: CH3CN, gradient: 20% B to 45% B in 35 min, flow rate 70 ml / min, 225 nm) and lyophilized to give compound 9 (CP9, 8 mg, TFA salt, confirmed). MS m / z: 617 [M+H] + .

[0307] Example 10 [ka]

[0308] Compound 10 (CP10, confirmed) was synthesized from CP9-7 and INT13 by a method similar to that for CP9 and purified by prep-HPLC (YMC-Triart C18-S12 nm, Phase A: water with 0.1% trifluoroacetic acid, Phase B: CH3CN, gradient: 15% B to 45% B in 30 min, flow rate 70 mL / min, 226 nm). LCMS: m / z: 616 [M+H] + .

[0309] Example 11 [ka]

[0310] CP11-3 was synthesized with INT7 and ST by a method similar to that for CP1-4.

[0311] Compound 11 (CP11, 7.1 mg) was synthesized using CP11-3 and INT13 in a similar manner to CP3. MS: m / z: 650 [M+H] + .

[0312] CP11 (3.08 mg) was separated using Prep-HPLC Gilson under the following conditions: column: CHIRAL ART Cellulose-SC, column (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), flow rate: 17 ml / min.

[0313] This gave the first peak compound 11A (CP11A, 2.8 mg, retention time: 5.510 min, confirmed) and compound 11B (CP11B, 2.4 mg, second peak, retention time: 8.137 min, confirmed).

[0314] Example 12 [ka]

[0315] CP9-5 (0.115 g) was separated by prep-HPLC under the following conditions. Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM=3:1)(0.1%DEA) / EtOH(50:50), Flow rate: 16 mL / min. CP10A-1 (83 mg, retention time 6.65 min) and CP10B-1 (61 mg, retention time 9.253 min) were obtained, respectively.

[0316] CP10A-3 was synthesized using CP10A-1 in a manner similar to that used for CP9-7.

[0317] CP10A (CP10A, confirmed) was synthesized in CP10A-3 by a method similar to that for CP3. Purification by prep-HPLC (Daisogel-C18, A: water with 0.1% trifluoroacetic acid, B: CH3CN, gradient: 15% B to 36% B in 38 min, flow rate 60 mL / min, 230 nm) and lyophilization afforded CP10A (26.4 mg, TFA salt). MS (ESI, m / z): 616 [M+H] + .

[0318] CP10B (CP10B, confirmed) was synthesized from CP10B-1 by a method similar to that for compound 10A. Purification by prep-HPLC (Daisogel-C18, Phase A: water with 0.1% trifluoroacetic acid, Phase B: CH3CN, gradient: 15% B to 35% B in 32 min, flow rate 60 mL / min, 230 nm) and lyophilization afforded CP10B (12.3 mg, TFA salt). MS (ESI, m / z:): 616 [M+H] + .

[0319] Example 13 [ka]

[0320] To a solution of SM (2.6 g) in DCM (80 ml) at rt was added Dess-Martin (6.1 g). The reaction mixture was stirred overnight. It was quenched with 5% sodium thiosulfate in saturated aqueous NaHCO3. The resulting biphasic mixture was vigorously stirred for 15 min and washed with DCM. The separated organic layer was worked up to give CP12A-1 (1.0 g). LCMS: m / z: 216 [M+H] + .

[0321] A solution of methyltriphenylphosphonium iodide (3.0 g) and t-BuOK (834.6 mg) in THF (37 ml) was heated to 45° C. at RT and stirred for 1 hour. CP12A-1 (800 mg) was added and stirred at RT overnight. The mixture was poured into water and extracted with EA. The separated organic layer was worked up to give CP12A-2 (350 mg). LCMS: m / z: 214 [M+H] + .

[0322] To a solution of CP12A-2 (40 mg) in dioxane (1.6 ml) was added 4 M HCl / dioxane (0.4 ml) at 0 °C, and the resulting mixture was stirred for 1 h. The reaction mixture was concentrated to give crude CP12A-3 (crude product). MS (ESI, m / z): 114.3 [M+H] + .

[0323] To a solution of INT6 (52 mg) in POCl3 (1 mL) was added DIEA (0.1 mL), and the resulting mixture was stirred at 110° C. for 1 hour. The reaction mixture was concentrated to give crude CP12A-4 (crude product).

[0324] To a solution of CP12A-4 (crude product, 0.188 mmol) in DCM (2 mL) at -40 °C, DIEA (162.4 mg) and CP12A-3 (crude product, 0.188 mmol) were added. The reaction mixture was stirred at -40 °C for 1 h. After completion, H2O was added to the reaction mixture and extracted with DCM. The separated organic layer was worked up to give CP12A-5 (30 mg). LCMS: m / z: 375 [M+H] + .

[0325] To a solution of CP12A-5 (30 mg) at room temperature, KPO (50.9 mg) and Pd(dppf)Cl (6 mg) in toluene / HO (10 / 1) (1.1 mL) were added. The reaction mixture was stirred overnight at 105 °C under a N atmosphere. After completion, HO was added to the reaction mixture and extracted with DCM. The separated organic layer was worked up to give CP12A (10 mg) as a yellow solid. MS (ESI, m / z: 339 [M+H] + . 1HNMR (300MHz, DMSO-d6): δ6.63(s,1H),5.46(s,1H),5.04-4.99(m,1H),4.75-4. 70(m,1H),4.04-3.97(m,2H),3.66-3.54(m,2H),3.25-3.21(m,1H),2.61(s,3H).

[0326] CP12-2 was synthesized in CP12A by a method similar to that for CP1-4.

[0327] Compound 12 (CP12, 1.4 mg, confirmed) was synthesized in CP12-2 by a method similar to that for CP2. LCMS: m / z: 600 [M+H] + .

[0328] Example 14 [ka]

[0329] Compound 13 (CP13) (8 mg, TFA salt, confirmed) was synthesized from CP1-3 and 13-a in a manner similar to that of CP5. LCMS: m / z: 629 [M+H] + .

[0330] Example 15 [ka]

[0331] A solution of 14-a (1.119 g), TEA (3.408 g), and BocO (2.483 g) in DCM was stirred at RT for 16 h. The reaction mixture was diluted with DCM and washed with water. The separated organic layer was worked up to give CP14-1 (1542 mg). LCMS: m / z: 230 [M+H] + .

[0332] CP14-8 was synthesized from CP14-1 by a method similar to that for CP12-2 (321 mg).

[0333] Compound 14 (CP14) was synthesized in CP14-8 by a method similar to that for CP3. It was separated by prep-HPLC (C18 column, A: water with 0.05% TFA, B: CH3CN, gradient: 25% B to 45% B in 40 min, flow rate 70 mL / min, 230 nm) to give compound 14A (CP14A, 12 mg, first peak, confirmed) and compound 14B (CP14B, 42 mg, second peak, confirmed). LCMS: m / z: 611 [M+H] + .

[0334] Example 16 [ka]

[0335] Compound 15 (CP15, confirmed) was synthesized in INT16 by a method similar to that for CP30.

[0336] Example 17 [ka]

[0337] To a solution of 16-a (249 mg) in MeOH (15 mL) was added Pd / C (235 mg). The solution was stirred under an H atmosphere for 6 hours, filtered, and the filtrate was concentrated to give CP16-1 (201 mg). MS (ESI, m / z:): 246 [M+H] + .

[0338] To a solution of CP16-1 (201 mg) in CH3CN (6 mL) was added HCl (4 M in 1,4-dioxane, 2 mL). The reaction mixture was stirred at RT for 1.5 hours and then concentrated. To the residue, CH3CN (5 mL) and aq. NaHCO3 (1 mL) were added, and the mixture was sonicated and then concentrated under reduced pressure. The residue was taken up in DCM and filtered. The filtrate was concentrated to give CP16-2 (168 mg). MS (ESI, m / z:): 146 [M+H] + .

[0339] A solution of CP16-2 (168 mg) in THF (10 mL) was cooled in an ice-ethanol bath. NaH (194 mg, 60% in oil) was added batchwise, followed by INT6 (331 mg). The reaction mixture was stirred for 2 hours. The mixture was quenched with two drops of water. The solution was purified by RP-flash to give CP16-3 (161 mg). MS (ESI, m / z:): 389 [M+H] + .

[0340] To a solution of CP16-3 (161 mg) in DCM (15 mL) was added DIEA (326 mg) and BOP-Cl (362 mg). The reaction mixture was stirred at RT for 24 h, quenched with water (30 mL), and extracted with DCM (30 mL). The separated organic layer was worked up to give CP16-4 (30 mg). MS (ESI, m / z:): 371 [M+H] + .

[0341] CP16-6 was synthesized using CP16-4 in a manner similar to that used for CP1-4.

[0342] Compound 16 (CP16, 1.2 mg, TFA salt, confirmed) was synthesized in CP16-6 in a similar manner to CP3. LCMS: m / z: 631 [M+H] + .

[0343] Example 18 [ka]

[0344] A solution of INT16-3 (352 mg) in THF (10 mL) was cooled to -70 °C under a N2 atmosphere. Methylmagnesium bromide (1 M in THF, 4 mL) was added dropwise, and the resulting mixture was stirred at -70 °C for 1 h, then quenched with water and extracted with EA. The separated organic layer was worked up to give CP17-1 (361 mg). MS (ESI, m / z:): 352 [M+H] + .

[0345] To a solution of CP17-1 (361 mg) in methanol (15 mL) under a H atmosphere was added Pd / C (354 mg). The reaction mixture was stirred at rt for 16 h, filtered, and the filtrate was concentrated to give CP17-2 (236 mg). MS (ESI, m / z:): 262 [M+H] + .

[0346] CP17-7 was synthesized from CP17-2 by a method similar to that for CP16-6.

[0347] Compound 17 (CP17, 19.1 mg, TFA salt, confirmed) was synthesized in CP17-7 by a method similar to that for CP3. LCMS: m / z: 647 [M+H] + .

[0348] Example 19 [ka]

[0349] CP18-6 was synthesized in 18-a by a method similar to that for CP16-8.

[0350] To a solution of CP18-6 (153 mg) in DMF (5 mL) was added CsF (466 mg). The reaction mixture was stirred at 40 °C for 4 hours. EA (40 mL) was added to the reaction mixture and washed with aq. NaHCO (30 mL). The separated organic layer was worked up and separated by Prep-HPLC (YMC-Triart C18-S12 nm, 50 mm × 250 mm, 7 μm, Phase A: 0.1% TFA in water, Phase B: CH3CN, gradient: 15% B to 43% B in 35 min, flow rate 70 mL / min, 220 nm), lyophilized, and identified compound 18A (CP18A, first peak, 70.9 mg, TFA salt, confirmed). MS (ESI, m / z:): 631 [M+H]. + , and Compound 18B (CP18B, second peak, 20.4 mg, TFA salt, confirmed). MS (ESI, m / z:): 631 [M+H] + .

[0351] Example 20 [ka]

[0352] DAST (2.38 g) was added to a solution of INT16-3 (821 mg) in DCM (20 mL) in an ice-ethanol bath and stirred for 1.5 hours. The solution was warmed to RT and stirred for 5 hours. The mixture was diluted with DCM (30 mL) and washed with aq. NaHCO3 (50 mL). The separated organic layer was worked up to give CP19-1 (565 mg). MS (ESI, m / z:): 358 [M+H] + .

[0353] To a solution of CP19-1 (565 mg) in MeOH (15 ml) under a H atmosphere, Pd(OH) / C (409 mg) was added. The reaction mixture was stirred at room temperature for 21 hours, filtered, and the filtrate was concentrated to give CP19-2 (439 mg). MS (ESI, m / z:): 268 [M+H] + .

[0354] Compound 19 (CP19, 39 mg, confirmed) was synthesized from CP19-2 in a similar manner to CP16. LCMS: m / z: 653 [M+H] + .

[0355] Example 21 [ka]

[0356] Compound 20 (CP20, confirmed) was synthesized by a method similar to that for CP9.

[0357] Example 22 [ka]

[0358] CP21-7A / 21-7B were synthesized in INT12 by a method similar to that for CP12-2, and separated by prep-TLC to give two isomers, CP21-7A (45 mg) and CP21-7B (38 mg). MS: m / z: 464 [M+H] + .

[0359] Compound 21 (CP21, confirmed) was synthesized from CP21-7A in a similar manner to CP3. LCMS: m / z: 613 [M+H] + .

[0360] Example 23 [ka]

[0361] CP22-1 was synthesized by a method similar to that for CP12A.

[0362] Compound 22 (CP22, 24.6 mg, TFA salt) was synthesized from CP22-1 in a similar manner to CP21. LCMS: m / z: 613 [M+H] + .

[0363] Example 24 [ka]

[0364] A solution of 23-a (3.02 g) in HCl (4 M in 1,4-dioxane, 30 mL) was stirred at RT for 3 h and concentrated to give CP23-1 (2.63 g). MS (ESI, m / z:): 88 [M+H] + .

[0365] A solution of CP23-1 (1.35 g), 2,2-difluoroethyl trifluoromethanesulfonate (1.42 g), and KCO (3.45 g) in CHCN (20 ml) was stirred at RT for 16 h. The mixture was diluted with water and extracted with EA. The organic layer was worked up to give CP23-2 (262 mg). MS (ESI, m / z:): 152 [M+H] + .

[0366] To a solution of CP1-3 (308 mg) and CP23-2 (125 mg) in THF (10 ml) was added t-BuONa (127 mg). The reaction mixture was stirred at RT for 1 h. The mixture was diluted with water and extracted with EA. The separated organic layer was worked up to give CP23-3 (56 mg). MS (ESI, m / z:): 460 [M+H] + .

[0367] Compound 23 (CP23, 16.0 mg, TFA salt, confirmed) was synthesized in CP23-3 by a method similar to that for CP3. LCMS: m / z: 609 [M+H] + .

[0368] Example 25 [ka]

[0369] To a solution of 24-a (14.20 g) in THF (150 mL) was added LAH (2.78 g) at 0 °C. The resulting mixture was stirred at RT for 1 h, quenched in an ice-water bath, filtered, and extracted with EA. The separated organic layer was worked up to give CP24-1 (11.01 g). MS (ESI, m / z): 222 [M+H] + .

[0370] A solution of CP24-1 (1.15 g) in THF (15 mL) was cooled to 0-5°C in an ice-water bath. NaH (218 mg) was added batchwise, and the resulting mixture was stirred at the same temperature for 30 min. Sodium bromidedifluoroacetate (801 mg) was added, and the mixture was stirred at RT for 16 h. The mixture was quenched with aq. NH4Cl and extracted with EA. The aqueous layer was concentrated to remove most of it. The remainder was worked up to give CP24-2 (739.9 mg). MS (ESI, m / z:): 316 [M+H] + .

[0371] To a solution of CP24-2 (589.2 mg) in MeOH (10 ml) under a H atmosphere, Pd / C (0.39 g) was added. The reaction mixture was stirred at RT for 16 h. The resulting mixture was worked up to give CP24-3 (395.1 mg). MS (ESI, m / z:): 226 [M+H] + .

[0372] A solution of CP24-3 (398.0 mg) in acetic acid (10 mL) was stirred at 110°C for 16 hours. The solution was concentrated to give CP24-4 (662.7 mg). MS (ESI, m / z:): 250 [M+H] + .

[0373] A solution of CP24-4 (217 mg) in borane (1 M in THF, 7 mL) was stirred at RT for 4 h. Quenching with methanol and workup gave CP24-5 (43.3 mg). MS (ESI, m / z:): 194 [M+H] + .

[0374] Compound 24 (CP24, confirmed) was synthesized in CP24-5 by a method similar to that for CP23. LCMS: m / z: 651 [M+H] + .

[0375] Example 26 [ka]

[0376] CP25-3 can be purchased or prepared according to conventional techniques.

[0377] Compound 25 (CP25, confirmed) was synthesized in CP25-3 by a method similar to that for CP23.

[0378] Example 27 [ka]

[0379] CP26 was synthesized in 26-a by a method similar to that for CP5.

[0380] CP26 (0.0171 g) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SA, column (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (70:30), flow rate: 18 mL / min. Compound 26A (0.0010 g, first eluting isomer, retention time 5.657 min, confirmed) and compound 26B (0.0069 g, second eluting isomer, retention time 6.437 min, confirmed). LCMS: m / z: 647 [M+H] + .

[0381] Example 28 [ka]

[0382] A solution of 27-a (432 mg) in THF (10 mL) was cooled to 0 °C, and borane (1 M in THF, 4 mL) was added dropwise. The resulting mixture was stirred at RT for 16 h. The resulting mixture was worked up to give CP27-1. LCMS: m / z: 130 [M+H] + .

[0383] Compound 27 (CP27) was synthesized in CP27-1 by a method similar to that for CP16. MS (ESI, m / z): 615 [M+H] + .

[0384] CP27 (26 mg) was separated by Prep-HPLC-Gilson under the following conditions: column: CHIRAL ART Cellulose-SA, column (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (75:25), flow rate: 18 mL / min.

[0385] Compound 27A (CP27A, 4.7 mg, first eluting isomer, retention time 5.533 min, confirmed) and compound 27B (CP27B, 3.9 mg, second eluting isomer, retention time 6.523 min, confirmed) were obtained.

[0386] Example 29 [ka]

[0387] A solution of 28-a (0.95 g) and BAST (1.45 g) in DCN (15 mL) was stirred at RT for 16 h. The solution was added to aq. NaHCO (10 mL). The separated organic layer was worked up to give CP28-1 (583 mg). MS (ESI, m / z:): 294 [M+H] + .

[0388] A solution of CP28-1 (583 mg) in methanol (10 mL) was added to NaBH4 (161 mg) and stirred at RT for 16 h. The reaction mixture was then heated to 60 °C and stirred for 11 h. The mixture was worked up to give CP28-2 (120 mg). MS (ESI, m / z): 252 [M+H] + .

[0389] To a solution of CP28-2 (120 mg) in DCM (5 ml) was added HCl (4 M in 1,4-dioxane, 2 mL). The reaction mixture was stirred at RT for 1 h. The reaction mixture was concentrated to give CP28-3 (72 mg). MS (ESI, m / z:): 152 [M+H] + .

[0390] Compound 28 (CP28, confirmed) was synthesized from CP28-3 in a similar manner to CP16. LCMS: m / z: 637 [M+H] + .

[0391] Example 30 [ka]

[0392] 29-a was synthesized with N-BOC-O-benzyl-L-serine by a method similar to INT16.

[0393] To a solution of 29-a (76.30 mg) in methanol (10 mL) under a H atmosphere, Pd / C (95 mg) was added. The reaction mixture was stirred at RT for 5 h. The resulting mixture was worked up to give CP29-1 (77 mg). MS (ESI, m / z:): 250 [M+H] + .

[0394] Compound 29 (CP29, confirmed) was synthesized in CP29-1 by a method similar to that for CP16. LCMS: m / z: 635 [M+H] + .

[0395] Example 31 [ka]

[0396] Compound 30 (CP30, confirmed) was synthesized in 30-a by a method similar to that for CP27.

[0397] Example 32 [ka]

[0398] To a solution of 31-a (1191 mg) in DMF (10 mL) was added NaH (205 mg) and iodomethane (1.16 g). The reaction mixture was stirred at RT for 18 h, quenched with water (20 mL), and extracted with EA (20 mL). The separated organic layer was worked up to give CP31-1 (602 mg). MS (ESI, m / z:): 274 [M+H] + .

[0399] To a solution of CP31-1 (602 mg) in THF (10 mL) was added LAH (84 mg), and the resulting mixture was stirred at RT for 30 minutes. To the resulting mixture were added 3 drops of water, 3 drops of 15% aqueous sodium hydroxide, and 8 drops of water. The solution was filtered. The filtrate was concentrated to give CP31-2 (424 mg). MS (ESI, m / z:): 246 [M+H] + .

[0400] Compound 31 (CP31, confirmed) was synthesized from CP31-2 in a similar manner to CP16. LCMS: m / z: 631 [M+H] + .

[0401] Example 33 [ka]

[0402] Compound 32 (CP32, confirmed) was synthesized from 32-a in a similar manner to CP16. LCMS: m / z: 631 [M+H] + .

[0403] Example 34 [ka]

[0404] CP33-2 can be purchased or prepared according to conventional techniques.

[0405] Compound 33 (CP33, confirmed) was synthesized from CP33-2 in a similar manner to CP27. LCMS: m / z: 643 [M+H] + .

[0406] Example 35 [ka]

[0407] CP14 (CP14, confirmed) was synthesized by a method similar to that for CP5. LCMS: m / z: 629 [M+H] + .

[0408] Example 36 [ka]

[0409] A solution of 35-a (5.15 g), DIEA (8.75 g), DMAP (0.35 g), and BocO (5.67 g) in DCM (100 mL) was stirred at 40 °C for 40 h. After completion, the mixture was worked up to give CP35-1 (3.29 g). MS (ESI, m / z): 336 [M+H] + .

[0410] A solution of CP35-1 (3 g) in toluene (50 mL) was cooled to -78 °C. Lithium triethylborohydride (1.4214 g) was added, and the resulting mixture was stirred at -78 °C for 4.5 h. DMAP (60 mg), DIEA (6.02 g), and trifluoroacetic anhydride (7.47 g) were then added, followed by stirring at RT overnight. The solution was diluted with NaHCO (100 mL). The separated organic layer was worked up to give CP35-2 (1.45 g). MS (ESI, m / z): 320 [M+H] + .

[0411] A solution of CP35-2 (1.45 g) in DCM (30 mL) was cooled to 10°C. Diethyl zinc (1 M in n-hexane, 13 mL) was added dropwise and stirred at RT for 30 minutes. The reaction mixture was cooled to 0°C, and then diiodomethane (5.19 g) was added dropwise. The temperature was gradually raised to RT and the mixture was stirred for 16 hours. The system was cooled. 200 mL of saturated ammonium chloride solution was added for extraction. The separated organic layer was worked up to give CP35-3 (1.27 g). MS (ESI, m / z): 234 [M+H] + .

[0412] A solution of CP35-3 (1.27 g), DMAP (0.71 g), and BocO (1.67 g) in DCM (20 mL) was stirred at RT for 16 h. The reaction mixture was heated to 40 °C and stirred for 24 h. The separated organic layer was worked up to give CP35-4 (578 mg). MS (ESI, m / z:): 334 [M+H] + .

[0413] Compound 35 (CP35, confirmed) was synthesized from CP35-4 by a method similar to that for CP29. MS: m / z: 629 [M+H] + .

[0414] Example 37 [ka]

[0415] A solution of 36-a (2.90 g), KCO (13.51 g), and phenylmethyl bromide (8.91 g) in CHCN (30 mL) was stirred at 80 °C for 24 h. After completion, the mixture was worked up to give CP36-1 (7.49 g). MS (ESI, m / z: 298 [M+H]. + .

[0416] To a solution of CP36-1 (7.49 g) in THF (20 mL) at 0 °C, LAH (0.90 g) was added batchwise, and the resulting mixture was stirred for 1 h and quenched with water, 15% NaOH (0.8 mL), and water (2.4 mL). The solution was worked up to give CP36-2 (4.56 g). MS (ESI, m / z:): 270 [M+H] + .

[0417] To a solution of CP36-2 (4.56 g) in THF (30 mL) at 0 °C, NaH (2396 mg) was added batchwise, and the resulting mixture was stirred at RT for 20 min. 2-Bromo-1,1-dimethoxyethane (5.80 g), DMAP (1.08 g), and TBAI (0.66 g) were added, and the resulting mixture was stirred at 70 °C for 17 h, quenched with water, and extracted with EA. The separated organic layer was worked up to give CP36-3 (5.06 g). MS (ESI, m / z:): 358 [M+H] + .

[0418] To a solution of CP36-3 (5.06 g) in ethanol (30 mL) under a H atmosphere, Pd(OH) / C (0.54 g) was added. The reaction mixture was stirred at RT for 92 h. The resulting mixture was worked up to give CP36-4 (2.34 g). MS (ESI, m / z:): 178 [M+H] + .

[0419] CP36 was synthesized in CP36-4 by a method similar to that for CP46, purified by prep-HPLC (Agela Durashell C18, A phase: water with 0.05% NH4OH, B phase: CH3CN, gradient: 25% B to 58% B in 35 min, flow rate: 40 ml / min, 225 nm), and lyophilized to give compound 36 (CP36, 0.0240 g, confirmed). MS (ESI, m / z:): 630 [M+H] + .

[0420] Example 38 [ka]

[0421] To a solution of 37-a (3.00 g) in 50 mL of methanol at 0 °C, thionyl chloride (75.81 mmol) was added dropwise, and the resulting mixture was stirred at RT for 16 h. The resulting mixture was concentrated to give CP37-1 (4.34 g, HCl salt). MS (ESI, m / z:): 130 [M+H] + .

[0422] To a solution of CP37-1 (4.34 g) in DCM (65 mL) was added TEA (68.34 mmol). The resulting white suspension was cooled to 0 °C, and 4-nitrobenzenesulfonyl chloride (6.09 g) was added batchwise. The mixture was stirred at RT for 16 h. The resulting mixture was quenched with water and extracted with DCM. The separated organic layer was worked up to give CP37-2 (8.02 g). MS (ESI, m / z): 313 [M-1] - .

[0423] To a solution of CP37-2 (3.01 g) in THF (50 mL) was added but-3-en-1-ol (0.98 g) and triphenylphosphine (5.07 g) at 0 °C. Subsequently, DIAD (3.84 g) was slowly added within 10 min. The reaction mixture was warmed to RT and stirred for 16 h. The resulting mixture was quenched with water and extracted with EA (100 mL). The separated organic layer was worked up to give CP37-3 (4.19 g).

[0424] A solution of CP37-3 (4.19 g) and Grubbs second generation catalyst (1.03 g) in DCM (200 mL) was stirred for 16 h at 50° C. After completion, the resulting mixture was worked up to give CP37-4 (3.427 g).

[0425] To a solution of CP37-4 (3.427 g) in MeOH (150 mL) was added CsCO (23.05 g) and thioglycolic acid (3.84 g). The mixture was stirred at RT for 16 h. The resulting mixture was worked up to give CP37-5, which was used directly in the next step. LCMS: m / z: 156 [M+H] + .

[0426] To a solution of CP37-5 in THF (30 mL) and water (30 mL) was added di-tert-butyl dicarbonate (2.94 g), the solution was stirred at RT for 1 h, and the resulting mixture was extracted with EA (100 mL). The separated organic layer was worked up to give CP37-6 (943 mg). MS (ESI, m / z): 256 [M+H] + .

[0427] To a solution of CP37-6 (943 mg) in THF (20 mL) was added LiAlH (200 mg), and the resulting mixture was stirred at RT for 2 h and quenched sequentially with water (0.2 mL), aq. 15% NaOH (0.2 mL), and water (0.6 mL). The solution was worked up to give CP37-7 (498 mg). MS (ESI, m / z): 228 [M+H] + .

[0428] Compound 37 (CP37, confirmed) was synthesized in CP37-7 by a method similar to that for CP16. MS (ESI, m / z): 613 [M+H] + .

[0429] Example 39 [ka]

[0430] To a solution of CP35-1 (847 mg) in THF (8 mL) was added methylmagnesium bromide (3 mmol, 3 M THF solution) at -78 °C. The reaction mixture was stirred for 3.5 h and quenched with aq. NH4Cl (20 mL). The organic layer was worked up to give CP38-1 (680 mg). MS (ESI, m / z): 352 [M+H] + .

[0431] To a solution of CP38-1 (680 mg) in DCM (8 mL) was added TFA (2 mL). The reaction mixture was stirred for 3.5 hours and concentrated to give CP38-2 (crude product), which was used in the next step. MS (ESI, m / z): 234 [M+H] + .

[0432] To a solution of CP38-2 (crude product) in chloroethane (5 mL) was added sodium triacetoxyborohydride (1.26 g). The reaction mixture was stirred for 5 hours, quenched with MeOH (10 mL) and water (2 mL), and concentrated to give CP38-3 (crude product), which was carried on to the next step. MS (ESI, m / z): 236 [M+H] + .

[0433] CP38-8 was synthesized using CP38-3 in a manner similar to that used for CP35.

[0434] CP38-11 was synthesized with CP38-8 by a method similar to that for CP16-7.

[0435] Compound 38 (CP38) was synthesized in CP38-11 by a method similar to that for CP35. The product was purified and separated by prep-HPLC (Agela Durashell C18, 30 mm x 250 mm, 10 μm, A phase: 0.05% NH4OH, B phase: CH3CN, gradient: 20% B to 50% B, 34 min, flow rate: 40 ml / min, 230 nm) and lyophilized to give compound 38A (CP38A, 16.6 mg, retention time: 35.9 min, confirmed) and compound 38B (CP38B, 3.1 mg, retention time: 37.5 min, confirmed). LCMS: 631 [M+H] + .

[0436] Example 40 [ka]

[0437] A solution of 39-a (53.03 g) in DCM (300 mL) was stirred at 0 °C. HCl (300 ml, 4 M solution in 1,4-dioxane) was added to the mixture at 0 °C, and the mixture was stirred at RT for 2 h. The mixture was concentrated to give crude product CP39-1 (35.12 g). MS: m / z: 92 [M+H] + .

[0438] A solution of CP39-1 (29.32 g), TEA (104.89 g), and p-methoxybenzaldehyde (112.00 g) in MeOH (300 mL) was stirred at 0° C. Sodium triacetoxyborohydride (137.83 g) was added to the mixture at 0° C. and stirred at 0° C. for 1 hour. The mixture was stirred at 40° C. for 24 hours. The reaction was quenched with water, extracted with EA, and worked up to give CP39-2 (25.50 g). MS: m / z: 332 [M+H]+ .

[0439] A solution of CP39-2 (5.50 g), TEA (2.28 g), DMAP (0.29 g), and TBDMSCl (2.54 g) in DCM (60 mL) was stirred at RT for 16 h. The mixture was quenched with water, extracted with DCM, and worked up to give CP39-3 (5.78 g). MS: m / z: 446 [M+H] + .

[0440] To a solution of CP39-3 (3.46 g) in DCM (40 mL) was added DAST (1.57 g) at -10 °C. The reaction mixture was stirred at -10 °C for 1 h. The mixture was quenched with 10% aqueous Na2CO3 solution and extracted with DCM. The organic phase was worked up and purified to give CP39-4 (1.57 g). MS: m / z: 448 [M+H] + .

[0441] To a solution of CP39-4 (1.57 g) in DMF (25 mL) was added CsF (6861 mg). The reaction mixture was stirred at 30 °C for 5 h. The solution was quenched with water, extracted with EA, and worked up to give CP39-5 (1048 mg). MS: m / z: 334 [M+H] + .

[0442] A solution of CP39-5 (300 mg) in THF (10 mL) was stirred at 0° C. To the mixture was added sodium hydride (139 mg, 60%) at 0° C. and stirred at RT for 0.5 h. To the mixture were added DMAP (32 mg), TBAI (44 mg), and bromoacetaldehyde dimethyl acetal (465 mg), and the mixture was stirred at 70° C. for 16 h. The mixture was cooled to RT, quenched with water, extracted with EA, and worked up to give CP39-6 (247 mg). MS: m / z: 422 [M+H] + .

[0443] Compound 39 (CP39) was synthesized from CP39-6 by a method similar to that for CP46. The compound was separated by prep-TLC (DCM / MeOH=10:1) to give the first eluted compound 39A (CP39A, 143 mg) and the second eluted compound 39B (17 mg). LCMS: m / z: 634 [M+H] + .

[0444] Example 41 [ka]

[0445] A solution of 40-a (20.42 g), acetic acid (600 mL), and water (600 mL) was cooled to 0-5°C. Sodium nitrite (25.14 g) was dissolved in water (50 mL) and slowly added to the above solution. The reaction mixture was stirred for 7 h. The resulting solution was diluted with 500 mL of EA and washed with water (200 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was dissolved in MeOH (600 mL) and water (600 mL) at RT, and K2CO3 (15.43 g) was added. The mixture was stirred for 24 h. The pH of the resulting solution was adjusted to 1-2 with 1N aqueous HCl. The mixture was extracted with EA. The combined organic layers were concentrated to give CP40-1 (23.37 g, crude product). The crude product was used in the next step. LCMS (ESI, m / z): 282 [M+H] + .

[0446] To a solution of CP40-1 (5.11 g) in MeOH (100 mL) was added thionyl chloride (2.1611 g) at 0 °C. The mixture was stirred under reflux for 16 hours. The resulting solution was concentrated. The residue was purified by silica gel column chromatography eluting with MeOH / DCM (0-5%, volume ratio) to give CP40-2 (1.98 g). LCMS (ESI, m / z): 296 [M+H] + .

[0447] CP40-2 (1.98 g) was dissolved in DCM (30 mL) under a N2 atmosphere at 0 °C. A solution of DAST (3.2420 g) in DCM (30 mL) was slowly added to the above solution. The resulting mixture was warmed to RT. The reaction was stirred for 20 h and then quenched with saturated NaHCO3 solution (100 mL) at 0-5 °C. The resulting solution was diluted with 100 mL of DCM. The organic phase was washed with brine, dried, filtered, and concentrated. The residue was purified by C18 gel chromatography eluting with H2O / CH3CN to give CP40-3 (747 mg). LCMS (ESI, m / z): 298 [M+H] + .

[0448] To a solution of CP40-3 (643 mg) in THF (3 mL) was added LAH (247 mg) at 0 °C. The mixture was stirred at 0 °C for 1 h and quenched with NaSO 10H O at 0-5 °C. The resulting mixture was filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography eluting with EA / HEX (0-50%, volume ratio) to give CP40-4 (423 mg). LCMS (ESI, m / z): 270 [M+H] + .

[0449] To a solution of CP40-4 (1.92 g) in MeOH (40 mL) was added palladium hydroxide (354 mg), purged with N2, and pressurized with H2. The mixture was stirred at RT for 20 h. Upon completion, the resulting mixture was filtered, and the filter cake was washed with MeOH. The filtrate was collected and the solvent was removed to give CP40-5 (1.31 g). The crude product was subjected to the next step. LCMS (ESI, m / z): 136 [M+H] + .

[0450] A solution of INT6 (894 mg), DIEA (828 mg), and POCl3 (432 mg) in toluene (20 mL) was stirred at 100 °C for 2 h. The resulting mixture was concentrated. At -10 to 20 °C, the residue was added to a mixture of CP40-5 (0.285 g) and DIEA (874 mg) in DCM (30 mL). The resulting mixture was warmed to RT. The reaction mixture was stirred for 0.5 h. The resulting solution was diluted with 50 mL of DCM. The organic phase was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by prep-TLC (EA:Hex = 1:2, volume ratio) to give CP40-6 (253 mg). LCMS (ESI, m / z): 397 [M+H] + .

[0451] To a solution of CP40-6 (2.09 g) in DMAc (40 mL) was added methylamine hydrochloride (532.8072 mg) and CS2CO3 (3.4282 g). The mixture was stirred at 80 °C for 3 h. After cooling to RT, the resulting mixture was diluted with water (400 mL) and filtered. The filter cake was dried to give CP40-7 (1.55 g). LCMS (ESI, m / z): 392 [M+H] + .

[0452] To a solution of CP40-7 (1.55 g) and TEA (2.06 g) in DMSO (60 mL) and DCM (30 mL) was added pyridine sulfur trioxide (2.00 g) at -10 to 20 °C. The resulting mixture was warmed to RT. The reaction mixture was stirred for 3 h. The resulting solution was diluted with 30 mL of DCM. The organic phase was washed with brine, dried, filtered, and concentrated. The residue was purified by silica gel column chromatography eluting with DCM / EA / HEX (1 / 1 / 1, volume ratio) to give CP40-8 (1.10 g). LCMS (ESI, m / z): 390 [M+H] + .

[0453] A solution of CP40-8 (1.10 g) and p-TsOH·HO (661 mg) in DMSO (30 mL) was stirred at 80 °C for 20 h. The solution was diluted with EA and washed with brine. The organic layer was dried over anhydrous NaSO, filtered, and concentrated. The residue was purified by silica gel column chromatography (eluent: 0-30% EA in hexane) to give CP40-9 (262 mg). LCMS (ESI, m / z): 372 [M+H] + .

[0454] CP40 was synthesized in CP40-9 by a method similar to that for CP46. The product was purified and separated by prep-HPLC (YMC-Triart C18-S12nm, 50 mm x 250 mm, 7 μm, Phase A: 0.05% aqueous ammonia, Phase B: CH3CN, gradient: 40% B to 73% B, 34 min, flow rate 70 mL / min, 224 nm) to give compound 40A (CP40A, first peak, 3.4 mg, confirmed) and compound 40B (CP40B, second peak, 49.2 mg, confirmed). MS (ESI, m / z): 632 [M+H]. + .

[0455] 1 HNMR(400MHz,DMSO-d6)δ7.75(dd,J=8.9,6.0Hz,1H),7.32(m,1H),7.09-6.95(m,2H),5.60(s,2H),5.34(dd,J=12.6,7.1Hz,1H),4.88(d,J=47.7 Hz,1H),4.43(s,1H),4.20-3.89(m,3H),3.12-3.07(m,3H),3.03(d,J=4 .2Hz,1H),2.83(d,J=6.4Hz,1H),2.16-1.64(m,14H),1.62-1.32(m,2H).

[0456] Example 42 [ka]

[0457] To a solution of 41-a (5539 mg) in ether (13 mL) was added NaH (405 mg) at 0 °C under a N atmosphere. The mixture was stirred at RT for 0.5 h. After cooling to 0 °C, trichloroacetonitrile (4 mL) was added dropwise. The resulting mixture was stirred at 0 °C for 1.5 h, and hexane (100 mL) was added. The mixture was filtered, and the filtrate was concentrated to give CP41-1 (9.78 g).

[0458] A solution of (S)-ethyl 3-hydroxybutyrate (2.6312 g) in DCM (56 mL) was stirred at RT under a N atmosphere. A solution of CP41-1 (9.78 g) in DCM (56 mL) was added dropwise. Upon completion, (1S)-(+)-camphor-10-sulfonic acid (0.55 g) was added. The resulting mixture was stirred overnight at RT. After quenching with aqueous NaHCO and workup, CP41-2 (7.28 g) was obtained.

[0459] To a solution of CP41-2 (7.28 g) in THF (30 mL) was added LiAlH (1.11 g) batchwise at 0 °C. The resulting mixture was stirred at RT overnight. The mixture was quenched with NaSO 10H O and filtered. The filtrate was concentrated and purified to give CP41-3 (1.98 g).

[0460] To a solution of CP41-3 (1.46 g) in THF (30 mL) were added 2-bromo-1,1-dimethoxyethane (3.95 g), TBAI (0.26 g), and NaH (1.17 g), and the resulting mixture was stirred at 80° C. for 16 h. The resulting mixture was quenched with water, extracted with EA, and worked up to give CP41-4 (2.03 g).

[0461] CP41-6 was synthesized in INT6 by a method similar to that for CP46.

[0462] A solution of CP41-6 (1.39 g), CP41-4 (1.79 g), and p-TsOH·HO (0.78 g) in DMSO (15 mL) was stirred at 80 °C for 5 h. Water was added to the mixture, and the mixture was extracted with EA. The separated organic layer was worked up to give CP41-7 (2.31 g). MS (ESI, m / z): 628 [M+H]+ .

[0463] A mixture of CP41-7 (2.31 g) and TFA (15 ml) was stirred at 120 °C overnight. The mixture was concentrated. NaOH (aq) and MeOH were added to the residue and stirred at RT for 1 h. The resulting mixture was extracted with DCM and EA for workup to give CP41-8 (1.06 g). MS (ESI, m / z): 388 [M+H] + .

[0464] To a mixture of CP41-8 (1.01 g) and DIEA (1033 mg) in DCM (15 mL) was added methanesulfonyl chloride (287 mg) dropwise. The resulting mixture was stirred at RT for 1 h and then diluted with water. The organic layer was separated, dried, and concentrated. The residue was dissolved in acetonitrile (15 mL). Cs2CO3 (2564 mg) was added to the resulting mixture and stirred at 60 °C for 3 h. The resulting mixture was diluted with water and EA (30 mL) and filtered through diatomaceous earth. The filtrate was extracted with EA and worked up to give CP41-9 (320 mg). MS (ESI, m / z): 370 [M+H] + .

[0465] CP41-9 (320 mg) was separated by chiral HPLC Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm × 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 18 mL / min. CP41-9A (0.16 g, first eluting isomer, retention time 4.933 min) and CP41-9B (second eluting isomer, retention time 11.277 min) were obtained.

[0466] Compound 41 (CP41, 18.2 mg, TFA salt, confirmed) was synthesized from CP41-9A by a method similar to that for CP46. MS (ESI, m / z): 630 [M+H] + .

[0467] Example 43 [ka]

[0468] To a solution of CP42-1 (3.08 g) in anhydrous THF (25 mL) was added sodium hydride (60% in oil, 0.59 g) at 0 °C under a N atmosphere, and the resulting mixture was stirred at RT for 30 min. A solution of methyl 2-bromopropionate (3.00 g) in anhydrous THF (5 mL) was added to the reaction mixture, and the mixture was stirred at RT for 1 h. Upon completion, the reaction mixture was diluted with EA and saturated NH4Cl, and workup afforded CP42-2 (4.05 g). MS: m / z: 342 [M+H] + .

[0469] To a solution of CP42-2 (3.55 g) in THF (40 mL) was added LAH (0.45 g) at 0 °C under a N atmosphere. The resulting mixture was stirred at RT for 1 h, quenched with ice water (5 mL), and filtered. The filtrate was concentrated and purified to give CP42-3 (2.11 g). MS: m / z: 314 [M+H] + .

[0470] A solution of CP42-3 (1.94 g), Pd / C (0.54 g, 10 wt%), and Pd(OH) / C (0.54 g, 10 wt%) in MeOH (60 mL) was stirred at RT under a H atmosphere for 5 h. The reaction mixture was filtered, and the filtrate was concentrated to give CP42-4 (693 mg). MS: m / z: 134 [M+H] + .

[0471] CP42-10 was synthesized from CP42-4 by a method similar to that for CP40-11.

[0472] CP42-10 (270 mg) was separated by Prep-HPLC-Gilson under the following conditions: column: CHIRAL ART Cellulose-SC, column (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), flow rate: 18 mL / min. CP42-11A (120 mg, first eluting isomer, retention time 5.557 min) and CP42-11B (116 mg, second eluting isomer, retention time 6.677 min) were obtained.

[0473] Compound 42 (CP42, confirmed) was synthesized from CP42-11A by a method similar to that for CP46. MS: m / z: 630 [M+H] + .

[0474] Example 44 [ka]

[0475] Compound 43 (CP43, confirmed) was synthesized from CP42-11B in a similar manner to CP46. MS: m / z: 630 [M+H] + .

[0476] Example 45 [ka]

[0477] To a solution of CP44-1 (517 mg) and DIEA (634 mg) in toluene (10 mL) was added POCl3 (0.24 mL). The reaction mixture was stirred at 80 °C for 1 h and concentrated to give a residue. To a solution of CP36-4 (338 mg) in DCM (10 mL) at 0 °C, DIEA (1 mL) was added. The reaction was stirred at RT for 0.5 h, diluted with water, extracted with DCM, and worked up to give CP44-2 (418 mg). MS m / z: 454 [M+H] + .

[0478] To a solution of CP44-2 (280 mg) and INT14 (217 mg) in 1,4-dioxane (2.5 mL) was added DIEA (249 mg, 1.93 mmol). The mixture was stirred at 100 °C for 44 h, quenched with water (30 mL), extracted with EA (30 mL), and worked up to give CP44-3 (226 mg). MS: m / z: 577 [M+H] + .

[0479] To a solution of CP44-3 (121 mg) and methylamine hydrochloride (203 mg) in DMAc (2 mL) was added CsCO (1311 mg). The mixture was stirred at 110 °C for 21 h, quenched with water (30 mL), extracted with EA (30 mL), and worked up to give CP44-4 (120 mg). MS: m / z: 587 [M+H] + .

[0480] Compound 44 (CP44, confirmed) was synthesized in CP44-4 by a method similar to that for CP46. MS: m / z: 629 [M+H] + .

[0481] Example 46 [ka]

[0482] Compound 45 (CP45, confirmed) was synthesized using CP10B-3 and INT10 in a similar manner to CP46. MS: m / z: 634 [M+H] + .

[0483] Example 47 [ka]

[0484] To a solution of CP39-3 (9.86 g) in DMSO (80 mL) and DCM (40 mL) at 0° C., TEA (19.84 g) and pyridine sulfur trioxide (14.15 g) were added. The reaction mixture was stirred at RT for 16 h. The mixture was diluted with water, extracted with EA, and worked up to give CP46-1 (10.79 g). MS: m / z: 444 [M+H] + .

[0485] To a solution of methyltriphenylphosphonium bromide (12.68 g) in THF (100 mL) was added potassium tert-butoxide (4.04 g) at 0°C. After stirring at RT for 1 h, CP46-1 (10.45 g) was added to the mixture. The reaction mixture was stirred at RT for 16 h. The mixture was diluted with water, extracted with EA, and worked up to give CP46-2 (7.72 g). MS: m / z: 442 [M+H] + .

[0486] To a solution of CP46-2 (7.70 g) in DMF (50 mL) was added CsF (8.12 g). The reaction mixture was stirred at RT for 16 h. The mixture was diluted with water, extracted with EA, and worked up to give CP46-3 (5.17 g). MS: m / z: 328 [M+H] + .

[0487] To a solution of CP46-3 (3.78 g) in THF (50 mL) was added sodium hydride (60% in oil, 1.84 g) at 0° C. After stirring for 1 hour, DMAP (0.13 g), TBAI (0.63 g), and bromoacetaldehyde dimethyl acetal (6.59 g) were added to the mixture. The reaction mixture was stirred at 70° C. for 23 hours. The reaction mixture was quenched with water, extracted with EA, and worked up to give CP46-4 (4.45 g). MS: m / z: 416 [M+H] + .

[0488] To a solution of CP46-4 (3.18 g) in MeOH (100 mL) was added Pd(OH) / C (2.96 g). The reaction mixture was stirred under H atmosphere at RT for 16 h. The mixture was filtered, and the filtrate was concentrated to give CP46-5 (1.5 g). MS: m / z: 178 [M+H] + .

[0489] Compound 46 (CP46, 31.8 mg, confirmed) was synthesized from CP46-5 and INT6 in a manner similar to that for CP39. MS: m / z: 630 [M+H] + .

[0490] Example 48 [ka]

[0491] A solution of 47-a (20.04 g) in THF (200 mL) was cooled to 0° C., and NaH (16.27 g), TBAI (4.45 g), DMAP (1.30 g), and BnBr (43.06 g) were added to the solution. The reaction mixture was stirred at RT for 16 h, quenched with water, extracted with ethyl acetate, and worked up to give CP47-1 (42.71 g).

[0492] To a solution of CP47-1 (18.64 g) in DCM (200 mL) at RT, m-CPBA (18.45 g) was added, and the resulting mixture was stirred for 16 h, filtered, and concentrated. The residue was purified to give CP47-2 (10.93 g). MS: 207 [M+H] + .

[0493] To a solution of CP47-2 (10.93 g) in MeOH (200 mL) was added benzylamine (17.15 g). The reaction mixture was stirred at 130 °C for 3 h under a N2 atmosphere. The mixture was cooled to RT. The mixture was concentrated and purified to give CP47-3 (10.65 g). MS: 314 [M+1] + .

[0494] A solution of CP47-3 (10.65 g), K2CO3 (14.96 g), TBAI (0.84 g), and BrBn (7.78 g) in ACN (120 mL) was stirred at RT for 16 h. The mixture was concentrated and purified to give CP47-4 (8.33 g). MS: 404 [M+H] + .

[0495] To a solution of CP47-4 (8.33 g) in DCM (100 mL) was added DAST (4.72 g). The reaction mixture was stirred at 0 °C for 3 h. The solution was diluted with sat. NaHCO3, extracted with EA, and worked up to give CP47-5 (5.65 g). MS: 406 [M+H] + .

[0496] To a solution of CP47-5 (5.65 g) in methanol (80 mL) under a H atmosphere, Pd(OH) / C (1.63 g) was added. The reaction mixture was stirred at 60 °C for 16 h. The resulting mixture was filtered, and the filtrate was concentrated to give CP47-6 (1.78 g). MS: 136 [M+H] + .

[0497] Compound 47 (CP47, 12.8 mg, confirmed) was synthesized from CP47-6 by a method similar to that for CP40. MS: 632 [M+H] + .

[0498] Example 49 [ka]

[0499] A solution of CP9-3 (1.058 g), CsCO (3001 mg), and CDNH HCl (510 mg) in DMF (15 mL) was stirred at 100 °C for 4 h. The reaction mixture was cooled to RT. The residue was diluted with water, extracted with EA, and worked up to give the crude product CP48-1, which was used directly. MS (ESI, m / z): 423 [M+H] + .

[0500] CP48-2 was synthesized with CP48-1 by a method similar to that for CP46-8.

[0501] CP48-2 (690 mg) was separated by Prep-HPLC-Gilson under the following conditions: column: CHIRAL ART Cellulose-SC, column (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) / EtOH = 50:50, flow rate: 18 ml / min, 220 nm, to give CP48-3 (second eluting isomer, retention time 11.7 min).

[0502] Compound 48 (CP48, confirmed) was synthesized in CP48-3 by a method similar to that for CP46. MS (ESI, m / z): 619 [M+H] + .

[0503] Example 50 [ka]

[0504] CP49 was synthesized in CP49-a by a method similar to that for CP40. MS: m / z: 632 [M+1] + .

[0505] CP49 (50 mg) was separated by prep-HPLC (Agela Durashell C18, 30 mm x 250 mm, 10 μm, A phase: 0.05% NH₃·H₂O, B phase: CH₃CN, gradient: 35 min, 25% B to 58% B, flow rate: 40 mL / min, 224 nm). Compound 49A (CP49A, first eluting isomer, retention time 30.8-33.39 min) and compound 49B (CP49B, second eluting isomer, retention time 33.64-35.75 min) were obtained. MS: m / z: 632 [M+1] + .

[0506] Example 51 [ka]

[0507] Compound 50 (CP50, confirmed) was synthesized from CP10B-3 in a similar manner to CP2. LCMS: m / z: 617 [M+H] + .

[0508] 1HNMR(400MHz,DMSO-d6)δ11.16-10.82(m,1H),8.02-7.90(m,1H),7.51-7.41(m,1H),7.36 (d,J=1.9Hz,1H),7.22-7.10(m,1H),5.58(d,J=53.2Hz,1H),5.38-5.26(m,1H),4.65-4.51 (m,2H),4.51-4.41(m,1H),4.13-3.94(m,2H),3.94-3.68(m,3H),3.64-3.49(m,1H),3.45 -3.22(m,3H),3.12-2.93(m,3H),2.63-2.44(m,3H),2.41-2.10(m,4H),2.09-1.89(m,2H).

[0509] Example 52 [ka]

[0510] Compound 51 (CP51, confirmed) was synthesized using CP10B-3 and INT1 in a similar manner to CP1. MS: m / z: 598 [M+H] + .

[0511] 1 HNMR(400MHz,DMSO-d6)δ7.79-7.68(m,1H),7.31-7.29(m,2H),7.18-7.08(m,1H),6.97-6.93(m,1H),5.32(s,2H),4.19-4.16(m,2H),3.88- 3.80(m,3H),3.53-3.50(m,2H),3.35-3.27(m,2H),3.02(s,3H),2.67- 2.51(m,4H),2.33-2.31(m,3H),2.22-2.18(m,4H),2.13-2.04(m,3H).

[0512] Example 53 [ka]

[0513] CP52 was synthesized in CP52-a using a method similar to that for CP94, and purified and separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), mobile phase: hexane (0.1% DEA) / EtOH (50:50), flow rate: 20 mL / min. Compound 52A (CP52A, 7.8 mg, 11.72 μmol, first eluting isomer, retention time 5.227 min, confirmed) and compound 52B (CP52B, 10.7 mg, 16.07 μmol, second eluting isomer, retention time 6.157 min, confirmed). LCMS: m / z: 666 [M+H] + .

[0514] Example 54 [ka]

[0515] To a mixture of 53-a (3.97 g) in THF (50 mL) was added DIEA (8.47 g) and (Boc)2O (5.20 g). The reaction mixture was stirred at RT for 3 h, diluted with EA and water, and worked up to give CP53-1 (4.17 g). MS: m / z: 246 [M+H] + .

[0516] To a solution of CP53-1 (4.17 g) in DCM (50 mL) was added DAST (23.90 mmol). The reaction mixture was stirred at 40 °C for 18 h and then worked up with saturated aqueous Na2CO3 (100 mL) at 0 °C to give CP53-2 (2.73 g). MS m / z: 268 [M+H] + .

[0517] To a solution of CP53-2 (2.52 g) in THF (20 mL) was added LAH (0.56 g) at -10 °C. The reaction mixture was stirred at RT for 0.5 h and quenched with water (1 mL), aq. NaOH (0.6 ml, 15% w / w), and water (3 mL). The mixture was filtered, and the filtrate was concentrated and purified to give CP53-3 (1589 mg). MS: m / z: 240 [M+H] + .

[0518] To a solution of CP53-3 (0.77 g) in acetonitrile (9 mL) was added HCl (3 mL, 4 mol / mL dioxane solution) at RT. The resulting mixture was stirred at RT for 2 h and then concentrated to give residue A. POCl3 (0.5 mL) was added to a solution of INT6 (889 mg) and DIEA (1232 mg) in toluene (10 mL). The reaction mixture was stirred at 80 °C for 2 h and concentrated to give residue B. To a solution of residue A and DIEA (2 mL) in DCM (10 mL), a solution of residue B in DCM (10 mL) was added. The reaction mixture was stirred at RT for 1.5 h, diluted with water, extracted with EA, and worked up to give CP53-4 (465 mg). MS: m / z: 401 [M+H] + .

[0519] Compound 53 (CP53, confirmed) was synthesized from CP53-4 by a method similar to that for CP47. MS: m / z: 636 [M+H] + .

[0520] Example 55 [ka]

[0521] CP54-5 was synthesized with CP54-1 by a method similar to that for CP47-10.

[0522] CP54-5 (133 mg) was separated by Prep-HPLC-Gilson under the following conditions: column: CHIRAL ART Cellulose-SC, column (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), flow rate: 17 mL / min. CP54-5A (53 mg, first eluting isomer, retention time 5.923 min) and CP54-5B (52 mg, second eluting isomer, retention time 8.129 min) were obtained.

[0523] Compound 54A (CP54A, confirmed) was synthesized from CP54-5A by a method similar to that for CP47. MS: m / z: 614 [M+H] + .

[0524] Compound 54B (CP54B, confirmed) was synthesized from CP54-5B in a similar manner to CP47. MS: m / z: 614 [M+H] + .

[0525] Example 56 [ka]

[0526] A solution of 55-a (1.58 g), DIEA (4.63 g), and 4-methoxybenzyl chloride (5.04 g) in DCM (20 mL) was stirred at RT for 18 h. The reaction mixture was quenched with water, extracted with DCM, and worked up to give CP55-1 (1.8874 g). MS: m / z: 352 [M+H] + .

[0527] To a solution of CP55-1 (2.7114 g) in THF (30 mL) was added NaH (1.6382 g, purity 60%) at RT under a N atmosphere. The reaction mixture was stirred for 1 h. DMAP (217 mg), TBAI (676 mg), and bromoacetaldehyde dimethyl acetal (5175 mg) were added to the mixture, and the reaction mixture was stirred at 70 °C for 17 h under a N atmosphere. Upon completion, the reaction mixture was quenched with water, extracted with EA, and worked up to give CP55-2 (2.8029 g, purity 70%). MS: m / z: 440 [M+H] + .

[0528] Compound 55 (CP55, confirmed) was synthesized from CP55-2 by a method similar to that for CP46. MS: m / z: 652 [M+H] + .

[0529] Example 57 [ka]

[0530] A solution of 56-a (5.03 g), TBAI (1.30 g), KCO (24.83 g), and BrBn (24.19 g) was stirred at RT for 16 h. The mixture was concentrated under reduced pressure and purified to give CP56-1 (9.2 g). MS: m / z: 270 [M+H] + .

[0531] To a solution of CP56-1 (8.8 g) in THF (100 mL) was added NaH (5.41 g, purity 60%). The reaction mixture was stirred at RT for 1 h. To the reaction mixture were added DMAP (0.39 g), TBAI (1.24 g), and bromoacetaldehyde dimethyl acetal (17.72 g). The resulting mixture was stirred at 75° C. for 16 h. The mixture was quenched with ice water, extracted with EA, and worked up to give CP56-2 (9.74 g). MS: m / z: 358 [M+H] + .

[0532] To a solution of CP56-2 (9.74 g) in methanol (100 mL) under a H atmosphere, Pd / C (2.8995 g) and Pd(OH) / C (2.0 g) were added. The reaction mixture was stirred at RT for 16 h. The resulting mixture was filtered and concentrated to give CP56-3 (4.65 g). MS: m / z: 178 [M+H] + .

[0533] CP56-6 was synthesized from CP56-3 by a method similar to that for CP46-8.

[0534] CP56-6 (1.32 g) was separated using Prep-HPLC Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 17 ml / min. CP56-6B (623 mg, first eluting isomer, retention time 6.69 min) and CP56-6A (0.61 g, second eluting isomer, retention time 8.708 min) were obtained. MS: m / z: 370 [M+H] + .

[0535] Compound 56A (CP56A, confirmed) was synthesized in CP56-6A by a method similar to that for CP46.

[0536] Compound 56B (CP56B, confirmed) was synthesized from CP56-6B by a method similar to that for CP46. MS: m / z: 630 [M+H] + .

[0537] Example 58 [ka]

[0538] A solution of 57-a (5.09 g), benzyl bromide (22.49 g), K2CO3 (12.03 g), and NaOH (3.45 g) in water (100 mL) was stirred at 100 °C for 3 h. The solution was extracted with EA and worked up to give CP57-1 (6641 mg). MS: m / z: 390 [M+H] + .

[0539] To a solution of CP57-1 (1029 mg) in THF (10 mL) was added DAST (508 mg) at RT, and the resulting mixture was stirred for 3 h. After quenching with 10% Na2CO3 solution and extraction with EA, workup gave CP57-2 (1046 mg). MS: m / z: 392 [M+H] + .

[0540] A solution of CP57-2 (6.62 g) in THF (60 ml) was stirred at 0 °C. LiAlH (1297 mg) was added to the mixture at 0 °C and stirred at RT for 2 h. The mixture was quenched with Na SO solution, filtered, concentrated and purified to give CP57-3 (4513 mg). MS: m / z: 288 [M+H] + .

[0541] A solution of CP57-3 (792 mg) in THF (15 mL) was stirred at 0° C. To the mixture was added sodium hydride (414 mg) at 0° C. and stirred at RT for 0.5 h. To the mixture were added DMAP (62 mg), tetrabutylammonium iodide (202 mg), and bromoacetaldehyde dimethyl acetal (1014 mg) and stirred at 70° C. for 6 h. The mixture was cooled to RT, quenched with water, extracted with EA, and worked up to give CP57-4 (503 mg).

[0542] 1 HNMR(400MHz,CDCl3)δ7.39(d,J=7.3Hz,4H),7.33(t,J=7.5Hz,4H),7.29-7.24(m,2H),4.72-4.52(m,1H),4.46(t,J =5.2Hz,1H),3.99-3.88(m,3H),3.60-3.42(m,5H),3.39(d,J=2.3Hz,6H),3.06-2.86(m,1H),1.20(d,J=6.9Hz,3H). MS:m / z:376[M+H] + .

[0543] A solution of CP57-4 (200 mg) and Pd(OH) / C (237 mg) in MeOH (10 mL) was stirred at RT under a H atmosphere for 16 h. The solution was filtered and concentrated to give crude product CP57-5 (103 mg). MS: m / z: 196 [M+H] + .

[0544] Compound 57 (CP57, confirmed) was synthesized from CP57-5 by a method similar to that for CP46. MS: m / z: 648 [M+H] + .

[0545] Example 59 [ka]

[0546] Compound 58 (CP58, confirmed) was synthesized in 58-a by a method similar to that for CP57. MS: m / z: 648 [M+H] + .

[0547] Example 60 [ka]

[0548] CP59-8 was synthesized using CP59-5 in a manner similar to that used for CP94-4.

[0549] CP59-8 (519 mg) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SA, column (2 cm × 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 18 mL / min. CP59A-9 (173 mg, first eluting isomer, retention time 4.587 min) and CP59B-9 (190 mg, second eluting isomer, retention time 5.067 min) were obtained.

[0550] Compound 59A (CP59A, confirmed) was synthesized in CP59A-9 by a method similar to that for CP46. MS: m / z: 660 [M+H] + .

[0551] Example 61 [ka]

[0552] To a solution of 60-a (2.162 g) in THF (20 mL) was added LAH (1222 mg) batchwise at -10 °C. The reaction mixture was stirred at 40 °C for 0.75 h and quenched with water (1.5 mL), aq. NaOH (1.5 ml, 15% w / w), and water (5 mL). The mixture was filtered, and the filtrate was concentrated. The residue was purified to give CP60-1 (2.852 mg). MS: m / z: 116 [M+H] + .

[0553] CP60-9 was synthesized using CP60-1 in a manner similar to that used for CP55-8.

[0554] CP60-9 (331 mg) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm × 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 18 mL / min. CP60-10 (138 mg, second eluting isomer, retention time 8.740 min) was obtained.

[0555] Compound 60 (CP60, confirmed) was synthesized from CP60-10 by a method similar to that for CP46. MS: m / z: 656 [M+H] + .

[0556] Example 62 [ka]

[0557] A solution of INT15 (1.005 g) in THF (100 mL) and DCM (100 mL) was added to Pd / C (459 mg). The mixture was stirred at RT under a H atmosphere for 3 hours. The solution was filtered, and the filtrate was concentrated to give CP61-1 (1053 mg). MS: m / z: 368 [M+H] + .

[0558] To a solution of CP61-1 (0.552 g) in DCM (50 mL) was added DAST (1.603 g) dropwise at 0 °C and stirred overnight at RT. The solution was quenched with 10% aqueous Na2CO3, extracted with DCM, and worked up to give CP61-2 (400 mg). MS: m / z: 390 [M+H] + .

[0559] CP61-4 was synthesized with CP61-2 by a method similar to that for CP46-10.

[0560] CP61-4 was separated by chiral high-performance liquid chromatography using the following conditions: CHIRAL ART Cellulose-SC, 20 mm x 250 mm, 5 μm, mobile phase: Hex (0.1% DEA) / EtOH (80:20), flow rate: 15 ml / min. CP61-5 (second eluting isomer, retention time: 9.189 min) was obtained. MS: m / z: 501 [M+H] + .

[0561] Compound 61 (CP61, confirmed) was synthesized from CP61-5 by a method similar to that for CP46. MS: m / z: 650 [M+H] + .

[0562] Example 63 [ka]

[0563] To a solution of CP61-1 (0.800 g) in DCM (20 mL) and THF (20 mL) was added NaBH4 (255 mg), and the resulting mixture was stirred at RT for 4 h. The solution was quenched with water, extracted with DCM, and worked up to give CP62-1 (735 mg). MS: m / z: 370 [M+H] + .

[0564] To a solution of triphenylphosphine (1085 mg) in DCM (25 mL) was added CCl (1008 mg) at 0 °C under N atmosphere, and the resulting mixture was stirred at 0 °C for 20 min. A solution of CP62-1 (0.636 g) in DCM (5 mL) was added dropwise at 0 °C and stirred overnight at RT. The mixture was diluted with DCM (30 mL) and washed with H O and saturated NaCl (aq). Workup afforded CP62-2 (338 mg). MS: m / z: 388 [M+H] + .

[0565] CP62-4 was synthesized using CP62-2 in a manner similar to that used for CP46-10.

[0566] CP62-4 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / IPA (50:50), Flow rate: 15 mL / min. CP62-4A (76 mg, first eluting isomer, retention time 6.223 min) and CP62-4B (66 mg, second eluting isomer, retention time 7.320 min) were obtained. MS: m / z: 499 [M+H] + .

[0567] Compound 62B (CP62B, confirmed) was synthesized from CP62-4B in a similar manner to CP46. MS: m / z: 648 [M+H] + .

[0568] Compound 62A (CP62A, confirmed) was synthesized from CP62-4A by a method similar to that for CP46. MS: m / z: 648 [M+H] + .

[0569] Example 64 [ka]

[0570] Compound 63 (CP63, confirmed) was synthesized from CP37-11 by a method similar to that for CP2. MS (ESI, m / z): 614 [M+H] + .

[0571] Example 65 [ka]

[0572] To a solution of CP35-1 (2.03 g) in THF (20 mL) was added dropwise cyclopropylbromomagnesium (12 mL, 1 M THF solution) at −78° C. The reaction mixture was stirred at −78° C. for 1.5 hours under a N2 atmosphere. The mixture was quenched with saturated aqueous NH4Cl. Dilution with EA and water and workup gave CP64-1 (1.80 g). MS: m / z: 378 [M+H] + .

[0573] To a solution of CP64-1 (1.80 g) in DCM (20 mL) was added TFA (5 mL) at RT, and the reaction mixture was stirred at RT overnight. The mixture was concentrated to give crude product CP64-2 (1.32 g). MS: m / z: 278 [M+H] + .

[0574] To a solution of CP64-2 (1.32 g) in DCE (20 mL) was added sodium triacetoxyborohydride (3.75 g) and anhydrous NaSO (5.73 g). The mixture was stirred at 42 °C for 2 days. The pH of the mixture was adjusted to 9 with aq. KCO. The mixture was extracted with DCM and worked up to give crude product CP64-3 (1.35 g). MS: m / z: 262 [M+H] + .

[0575] To a solution of CP64-3 (1.35 g) in THF (15 mL) was added di-tert-butyl dicarbonate (1.57 g). The reaction mixture was stirred overnight at 44 °C under a N2 atmosphere. The mixture was diluted with EA (50 mL) and water (30 mL). The organic layer was worked up to give CP64-4 (683 mg). MS: m / z: 362 [M+H] + .

[0576] To a solution of CP64-4 (683 mg) in MeOH (20 mL) was added Pd(OH) / C (0.31 g). The reaction mixture was stirred under an H atmosphere at 44 °C for 24 h. The mixture was filtered, and the filtrate was concentrated to give CP64-5 (0.47 g). MS: m / z: 272 [M+H] + .

[0577] Compound 64 (CP64, confirmed) was synthesized from CP64-5 by a method similar to that for CP16. MS: m / z: 657 [M+H] + .

[0578] Example 66 [ka]

[0579] Compound 65 (CP65, confirmed) was synthesized by a method similar to that for CP64. MS m / z: 645 [M+H] + .

[0580] Example 67 [ka]

[0581] To a solution of INT7 (0.63 g) in MeOH (10 ml), HCl (5 mL, 1,4-dioxane solution, 4 M) was added. The reaction mixture was stirred at RT for 2.5 h and concentrated to give a residue. At -10 °C, NaH (550 mg, 60% in oil) was added batchwise to the residue mixture in THF (15 mL), and CP66-1 (899 mg) was added to the mixture. The reaction mixture was stirred at RT for 20 h, quenched with a small amount of water, and concentrated to give a residue. DCM:MeOH = 10:1 (20 mL) was added to the residue. After stirring for 5 min, the mixture was filtered, and the filtrate was concentrated to give CP66-2 (1483 mg). MS (ESI, m / z): 442 [M+H] + .

[0582] To a solution of CP66-2 (1483 mg) in DCM (20 mL) was added DIEA (1.51 g) and BOP-Cl (1.68 g). The reaction mixture was stirred at RT for 21 h, quenched with water, and extracted with DCM. The organic layer was washed with brine, dried, concentrated, and purified by prep-TLC to give CP66-3 (190 mg). MS (ESI, m / z): 424 [M+H] + .

[0583] To a solution of CP66-3 (190 mg) in DMF (1 mL) and THF (1 mL) was added INT14 (127 mg), DABCO (18 mg), and Cs2CO3 (216 mg) at 30 °C, and the resulting mixture was stirred for 20 h. The mixture was quenched with water and extracted with EA. The organic layer was washed with brine, dried, concentrated, and purified by prep-TLC to give CP66-4 (206 mg). MS (ESI, m / z): 547 [M+H] + .

[0584] A mixture of CP66-4 (116 mg), 66-a (98 mg), DPEPhosPdCl (22 mg), and CsCO (213 mg) in toluene (3 mL) was stirred at 105 °C for 19 h under a N atmosphere. Water was added to the reaction mixture, and the mixture was extracted with EA. The organic layer was washed with brine, dried, concentrated, and purified by prep-TLC to give CP66-5 (148 mg). MS (ESI, m / z): 757 [M+H] + .

[0585] To a solution of CP66-5 (148 mg) in DCM (6 mL) was added TFA (2 mL). The reaction mixture was stirred at RT for 2 h and concentrated. The residue was purified by prep-HPLC (Agela Durashell C18, 30 mm × 250 mm, 10 μm, Phase A: 0.1% TFA in water, Phase B: CH3CN, gradient: 15% B to 40% B, 37 min, flow rate: 60 mL / min, 295 nm) and lyophilized to give CP66 (60 mg, TFA salt). MS (ESI, m / z): 657 [M+H] + .

[0586] CP66 (60 mg, TFA salt) was separated by Prep-HPLC-Gilson under the following conditions: column: CHIRAL ART Amylose-SA, column (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), flow rate: 20 mL / min. Compound 66A (CP66A, 22.3 mg, first eluting isomer, retention time 3.990 min, confirmed) and compound 66B (CP66B, 15.1 mg, second eluting isomer, retention time 5.103 min, confirmed).

[0587] Example 68 [ka]

[0588] Compound 67 (CP67, confirmed) was synthesized from CP37-7 by a method similar to that for CP21. MS m / z: 609 [M+H] + .

[0589] Example 69 [ka]

[0590] Compound 68 (CP68, confirmed) was synthesized by the CP9 step. LCMS: m / z: 642 [M+H] + .

[0591] Example 70 [ka]

[0592] Compound 69 (CP69, trifluoroacetate salt, confirmed) was synthesized by the procedure of CP68. LCMS: m / z: 630 [M+H] + .

[0593] Example 71 [ka]

[0594] CP70-2 was synthesized using 4-amino-1-butanol and INT6 as starting materials, following the steps of CP42-6.

[0595] To a solution of CP70-2 (97 mg) in trimethyl orthoformate (3 mL), p-TsOH·HO (62 mg) was added, and the mixture was purged with N and stirred at 100 °C for 0.5 h. The reaction mixture was cooled to RT, diluted with EA and water, and the separated organic layer was concentrated and purified to give CP70-3 (157 mg). MS: m / z: 356 [M+H] + .

[0596] Compound 70 (CP70, TFA salt, confirmed) was synthesized in CP70-3 by the procedure of CP42. LCMS: m / z: 616 [M+H] + .

[0597] Example 72 [ka]

[0598] To a solution of 71-a (1.03 g) and TEA (7.76 g) in DCM (10 mL) and DMSO (20 mL) was added sulfur trioxide pyridine complex (7.36 g) at 0 °C, and the resulting mixture was stirred for 4 h. The residue was diluted with DCM and washed with sodium thiosulfate solution (10%), 5% citric acid solution, and saturated sodium chloride solution (80 mL). The resulting solution was dried, filtered, and concentrated to give CP71-1 (1.06 g).

[0599] CP71-5 was synthesized from CP71-1 by a method similar to that for INT15.

[0600] Compound 71 (CP71, confirmed) was synthesized from CP71-5 in a similar manner to CP46. LCMS: m / z: 598 [M+H] + .

[0601] Example 73 [ka]

[0602] Under a N2 atmosphere, 72-a (1.36 g) was added to allylmagnesium chloride solution (2 M in THF, 15 mL) at room temperature and stirred at 80°C for 20 hours. The reaction mixture was quenched with saturated ammonium chloride solution (60 mL) and diethyl ether (80 mL). The organic layer was separated and washed with acetic acid solution (1%), saturated NaHCO3 solution, and saturated sodium chloride solution. The resulting solution was dried, filtered, and concentrated to give CP72-1 (2.20 g).

[0603] To a solution of CP72-1 (0.85 g), styrene (2.50 g), and tetraethyl titanate (1.14 g) in DCE (20 mL) was added Grubbs second-generation catalyst (0.39 g). The mixture was purged with N2 and stirred at 70 °C for 16 h. After completion, the mixture was concentrated and purified to give CP72-2 (0.61 g).

[0604] To a solution of CP72-2 (0.543 g) and CP71-3 (0.282 g) in DMSO (10 ml) was added p-TsOH·HO (160 mg). The mixture was purged with N and stirred at 80 °C for 16 h. The reaction mixture was cooled to RT, diluted with EA and water, and the resulting mixture was separated. The collected organic layer was concentrated and purified to give CP72-3 (197 mg). MS: m / z: 456 [M+H] + .

[0605] Compound 72 (CP72, confirmed) was synthesized in CP72-3 by the steps of CP71. LCMS: m / z: 612 [M+H] + .

[0606] Example 74 [ka]

[0607] To a solution of CP36-9 (228 mg), 73-a (596 mg), and CsCO (482 mg) in toluene (10 mL) and water (2.5 mL), cataCXium A Pd G3 (82 mg) was added, and the mixture was purged with N and stirred at 100 °C for 16 h. After completion, the mixture was diluted with EA and water. The separated organic layer was concentrated and purified to give compound 73 (CP73, confirmed). MS: m / z: 625 [M+1] + .

[0608] Example 75 [ka]

[0609] Compound 74 (CP74, confirmed) was synthesized from CP9-6 and 74-a in a similar manner to CP46. MS: m / z: 628 [M+H] + .

[0610] Example 76 [ka]

[0611] To a solution of CP10B-3 (64 mg), 75-a (64 mg), and CsCO (137 mg) in toluene (10 mL) and water (2.5 mL) was added bis(diphenylphosphinophenylether)palladium(II) dichloride (10 mg). The mixture was purged with N and stirred at 105 °C for 16 h. After completion, the mixture was diluted with EA and water. The organic layer was separated and concentrated to give CP75-2 (133 mg). MS: m / z: 723 [M+1] + .

[0612] To a solution of CP75-2 (133 mg) in DCM (5 mL) was added TFA (1.5 mL). The reaction mixture was stirred at RT for 2 h. Upon completion, the reaction mixture was concentrated. The residue was diluted with EA and saturated NaHCO3. The separated organic layer was concentrated and purified to give compound 75 (CP75, confirmed). MS: m / z: 623 [M+H] + .

[0613] Example 77 [ka]

[0614] To a solution of 76-a (5094 mg) in THF (50 mL) at 0 °C was added lithium aluminum deuteride (1508 mg). The mixture was stirred at 0 °C for 4 h. The mixture was quenched with 1.5 mL of water, 1.5 mL of 15% NaOH, 4.5 mL of water, and a small amount of anhydrous NaSO. The mixture was filtered and concentrated to give 76-b (3285 mg). MS: m / z: 109 [M+H] + .

[0615] Compound 76 (CP76, confirmed) was synthesized using CP76-b in a similar manner to CP9. MS: m / z: 618 [M+H] + .

[0616] Example 78 [ka]

[0617] To a solution of CP83-10 (0.698 g) in DCM (5 mL) at 0 °C was added DAST (0.493 g). The mixture was stirred at 0 °C for 1.5 h and quenched with saturated NaHCO (aq.). Workup by extraction with DCM gave CP77-1 (0.206 g). MS: m / z: 372 [M+H] + .

[0618] Compound 77 (CP77, 0.0013 mg, TFA salt, confirmed) was synthesized in CP77-1 by a method similar to that for CP46. MS: m / z: 632 [M+H] + .

[0619] Example 79 [ka]

[0620] A mixture of CP113-3 (1.295 g) and trifluoroacetic acid (5 ml) was stirred at RT overnight. The reaction mixture was concentrated. The resulting mixture was diluted with PE and EA (10:1) and filtered. The filter cake was concentrated to give CP78-1 (1024 mg). MS: m / z: 342 [M+H] + .

[0621] A mixture of CP78-1 (0.201 g) in acetic acid (2 mL) and acetic anhydride (1 mL) was stirred at 80° C. for 3 days. The mixture was quenched with HO and extracted with DCM and MeOH (10:1) to give CP78-2 (206 mg) after workup. MS: m / z: 384 [M+H] + .

[0622] Compound 78 (CP78, confirmed) was synthesized in CP78-2 by a method similar to that for CP46. MS: m / z: 644 [M+H] + .

[0623] Example 80 [ka]

[0624] A solution of 79-a (3.58 g), 4-methoxybenzylamine (5.62 g), DIEA (10.0170 g), and HATU (15.18 g) in DCM (80 mL) was stirred overnight at RT. The mixture was extracted with DCM and worked up to give CP79-1 (1.05 g). MS: m / z: 210 [M+H] + .

[0625] LAH (0.308 g) was added to THF (10 mL) at 0° C. The mixture was stirred at 0° C. for 15 minutes, and aluminum chloride (1.071 g) was added. The mixture was stirred at 0° C. for 30 minutes, and CP79-1 (0.74 g) was added. The mixture was stirred at 0° C. for 30 minutes. The mixture was quenched with NaOH (aq., 0.3 mL, 15%) and extracted with DCM. The mixture was washed with NH4Cl, dried, and concentrated to give CP79-2 (0.39 g). MS: m / z: 196 [M+H] + .

[0626] A solution of INT6 (0.603 g), DIEA (1.4840 g), and POCl3 (2.6320 g) in toluene (20 mL) was stirred at 80 °C for 1 hour. The mixture was concentrated to give a mixture. CP79-2 (0.39 g) was added to a solution of the mixture and DIEA (2.6320 g) in DCM (5 mL) at 0 °C. The mixture was stirred at 0 °C overnight. The residue was concentrated and purified to give CP79-3 (238 mg). MS: m / z: 457 [M+H] + .

[0627] A solution of CP79-3 (0.218 g) in TFA (3 mL) was stirred at 60° C. for 1 hour. The mixture was concentrated to give CP79-4 (0.298 g). MS: m / z 337: [M+H] + .

[0628] Compound 79 (CP79, confirmed) was synthesized in CP79-4 by the steps of CP71. LCMS: m / z: 630 [M+H] + .

[0629] Example 81 [ka]

[0630] To a solution of 80-a (5.01 g) and L-proline (3.66 g) in MeCN (50 mL) and methanol (50 mL) at 0 °C, a selective fluorination reagent (27.58 g) was added. The mixture was stirred at 55 °C overnight. The mixture was concentrated and purified to give CP80-1 (3.284 g).

[0631] Compound 80 (CP80, confirmed) was synthesized in CP80-1 by a method similar to that for CP71. MS: m / z: 630 [M+H] + .

[0632] Example 82 [ka]

[0633] To a solution of CP83-10 (0.1 g) in DCM (10 mL) was added NaHCO3 (29 mg) and Dess-Martin oxidant (139 mg) at RT, and the resulting mixture was stirred for 1 h. The reaction was filtered, and the filtrate was concentrated to give the crude product. The crude product was diluted with DCM (2 mL), and m-CPBA (65 mg) was added at RT, followed by stirring for 1 h. Workup was carried out by quenching with sodium thiosulfate and extraction with DCM to give CP81-1 (173 mg). The crude product was used directly in the next step. MS (ESI, m / z): 400 [M+H] + .

[0634] A solution of molecular sieves 4A, CP81-1 (172 mg), DIEA (160 mg), and INT14 (109 mg) in toluene (5 mL) was stirred at 80 °C for 16 h under a N atmosphere. The reaction mixture was cooled to RT. The reaction mixture was concentrated and purified to give CP81-2 (65 mg). MS (ESI, m / z): 479 [M+H] + .

[0635] To a solution of CP81-2 (0.052 g) in DCM (1 mL) at 0 °C under a N atmosphere, DAST (0.5 mL) was added batchwise within 2 min. The mixture was stirred at RT for 3 h and quenched with saturated NaHCO solution. Workup by extraction with DCM gave CP81-3 (10 mg). MS (ESI, m / z): 501 [M+H] + .

[0636] Compound 81 (CP81, confirmed) was synthesized in CP81-3 by a method similar to that for CP46. MS (ESI, m / z): 650 [M+H] + .

[0637] Example 83 [ka]

[0638] Compound 82 (CP82, confirmed) was synthesized from CP82-1 by a method similar to that for CP46. MS: m / z: 630 [M+H] + .

[0639] Example 84 [ka]

[0640] To a solution of 83-a (50.04 g) in THF (400 mL) was added NaH (15.54 g) at -20 °C. The mixture was stirred at -20 °C for 2 hours. To the reaction mixture was added n-BuLi (210 mL). The mixture was stirred at -20 °C for 1 hour. To the reaction mixture was added a solution of benzyl 2-bromoethyl ether (81.59 g) in THF (100 mL). The mixture was stirred at RT overnight. The mixture was diluted with sat. NaH4Cl (aq.) and water, extracted with EA, and worked up to give CP83-1 (92.29 g). MS: m / z: 265 [M+H] + .

[0641] A solution of CP83-1 (48.77 g) in dibenzylamine (200 mL) was stirred overnight at 100 °C under a N atmosphere. The mixture was quenched with water, extracted with EA, and worked up to give CP83-2 (76.66 g). MS: m / z: 416 [M+H] + .

[0642] To a solution of CP83-2 (76.66 g) in THF (200 mL) at 0 °C was added NaBH (12.74 g). The mixture was stirred at RT for 5 h. The mixture was quenched with MeOH (20 mL) and water, extracted with EA, and worked up to give CP83-3 (47.61 g). MS: m / z: 418 [M+H] + .

[0643] To a solution of CP83-3 (41.16 g) and imidazole (27.32 g) in DMF (50 mL) at 0° C., TBDNSCl (45.26 g) was added. The mixture was stirred at RT for 2 h. The mixture was quenched with water, extracted with EA, and worked up to give CP83-4 (57.45 g). MS: m / z: 532 [M+H] + .

[0644] To a solution of CP83-4 (57.45 g) in THF (400 mL) at -40°C, diisobutylaluminum hydride (250 mL) was added. The mixture was stirred at -20°C to -40°C for 3 hours. The mixture was quenched with EA (300 mL) and potassium sodium tartrate solution. The mixture was warmed to RT and stirred vigorously for 4 hours. When the solution became clear, it was extracted with EA and worked up to give CP83-5 (8.29 g). MS: m / z: 518 [M+H] + .

[0645] A solution of CP83-5 (8.29 g), Pd / C (4.07 g), and Pd(OH) / C (5.34 g) in IPA (200 mL) was stirred overnight at 65 °C under an H atmosphere. The mixture was filtered, and the filtrate was collected and concentrated to give CP83-6 (3.989 g). MS: m / z: 248 [M+H] + .

[0646] A solution of INT6 (4.45 g), phosphoryl chloride (8 mL), and DIEA (8 mL) in toluene (50 mL) was stirred at 80° C. overnight. The reaction mixture was concentrated to obtain a mixture. To a solution of the mixture and DIEA (2 mL) in DCM (10 mL) at 0° C., CP83-6 (3.53 g) was added. The mixture was stirred at 0° C. for 1 hour. The resulting CP83-7 (3.78 g) was purified. MS: m / z: 509 [M+H] + .

[0647] A solution of CP83-7 (3.59 g), methylamine hydrochloride (2.62 g), and DIEA (7.07 g) in DMA (20 mL) was stirred at 80 °C for 3 h. The mixture was quenched with water, extracted with EA, and worked up to give CP83-8 (4.447 g). MS: m / z: 504 [M+H] + .

[0648] To a solution of CP83-8 (4.29 g) and TEA (7.97 g) in DCM (6 mL) and DMSO (12 mL) at -40 °C, pyridine sulfur trioxide (4.74 g) was added. The mixture was stirred at RT for 3 h, quenched with sat. NaSO (aq.), extracted with DCM, and worked up to give CP83-9 (2.301 g). MS: m / z: 502 [M+H] + .

[0649] CP83-9 (2.301 g) and p-TsOH HO (0.914 g) in DMSO (10 mL) were stirred overnight at 80 °C and purified to give CP83-10 (0.726 g). MS: m / z: 370 [M+H] + .

[0650] To a solution of CP83-10 (0.283 g) in DCM (5 mL) was added DAST (0.269 g) at 0 °C. The mixture was stirred at 0 °C for 1.5 h, quenched with sat. NaHCO (aq.), extracted with DCM, and worked up to give CP83-11 (0.047 g). MS: m / z: 372 [M+H] + .

[0651] Compound 83 (CP83, confirmed) was synthesized from CP83-11 by a method similar to that for CP46. MS: m / z: 632 [M+H] + .

[0652] Example 85 [ka]

[0653] To a solution of CP83-10 (0.101 g) and imidazole (0.140 g) at 0° C., TBDNSCl (0.138 g) was added. The mixture was stirred at RT for 2 h. The mixture was quenched with water, extracted with EA, and worked up to give CP84-1 (0.057 g). MS: m / z: 484 [M+H] + .

[0654] CP84-3 was synthesized with CP84-1 by a method similar to that for CP46-10.

[0655] Racemic CP84-3 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRALPAK-IG, 20 mm x 250 mm, 5 μm; Mobile phase: (Hex:DCM=3:1) (0.1% DEA) / EtOH (50:50); Flow rate: 20 mL / min, 220 nm. CP84-4A (first eluting isomer, retention time 5.767 min) and CP84-4 (second eluting isomer, retention time 7.067 min, 0.015 g) were obtained. MS: m / z: 595 [M+H] + .

[0656] A solution of CP84-4 (0.015 g), INT13 (0.038 g), cataxium A Pd G3 (0.020 g), and Cs2CO3 (0.043 g) in toluene (5 mL) and water (1 mL) was stirred overnight at 100 °C under a N2 atmosphere. Water was added to the mixture, which was then extracted with EA. The organic layer was worked up to give CP84-5 (0.026 g). MS: m / z: 1065 [M+H] + .

[0657] Compound 84 (CP84, confirmed) was synthesized in CP84-4 by a method similar to that for CP83. MS: m / z: 630 [M+H] + .

[0658] Example 86 [ka]

[0659] To a solution of CP61-1 (0.508 g) in DMF (10 mL) was added 2-[(fluoromethyl)sulfonyl]pyridine (0.286 g), and the resulting mixture was stirred at -50 °C under a N2 atmosphere. Potassium tert-butoxide (0.239 g) was added. The solution was stirred at RT for 4 h. The mixture was diluted with EA, washed with NH4Cl(aq) (50 mL), HO (50 mL), and saturated NaCl(aq), and concentrated. 10 mL of PE and 2 mL of EA were added, and the resulting mixture was stirred for 1 h. The mixture was filtered to give CP85-1 (346 mg). MS: m / z: 384 [M+H] + .

[0660] To a solution of CP85-1 (346 mg) in DCM (10 mL) at 0 °C, m-CPBA (0.367 g) was added batchwise, and the resulting mixture was stirred at RT for 2 h. The mixture was diluted with DCM (50 mL) and washed with water, saturated NaHCO3 solution, and saturated NaCl (aq). The organic layer was dried and concentrated to give CP85-2 (365 mg, crude product), which was used in the next step. MS: m / z: 400 [M+H] + .

[0661] A solution of CP85-2 (365 mg), INT14 (0.243 g), and DIEA (389 mg) in toluene (15 mL) was stirred at 85 °C for 16 h. The mixture was cooled to RT, diluted with EA, and washed with water and NaCl (aq). The organic layer was concentrated. The residue was purified by prep-TLC (DCM / MeOH = 15:1) to give CP85-3 (174 mg) and CP85-4 (79 mg). MS: m / z: 495 [M+H] + .

[0662] Compound 85 (CP85, confirmed) was synthesized from CP85-3 in a similar manner to CP46. LCMS: m / z: 644 [M+H] + .

[0663] Example 87 [ka]

[0664] Compound 86 (CP86, confirmed) was synthesized from CP85-4 by a method similar to that for CP46. MS: m / z: 644 [M+H] + .

[0665] Example 88 [ka]

[0666] To a solution of 87-a (34.11 g) in DMF (350 mL), carbonyldiimidazole (39.17 g) was added, and the resulting mixture was stirred at RT for 16 h. At 0 °C, potassium malonate monomethyl salt (39.34 g), magnesium chloride (47.90 g), and TEA (51.57 g) were added. The solution was stirred at RT for 20 h. The solution was filtered, quenched with water, extracted with EA, and worked up to give CP87-1 (40.33 g). MS: m / z: 260 [M+H] + .

[0667] To a solution of CP87-1 (46.4720 g) in MeOH (400 mL), NaBH4 (2.300 g) was added, and the resulting mixture was stirred at 0 °C for 3 h. The solution was diluted with EA and worked up to give CP87-2 (34.04 g). MS: m / z: 262 [M+H] + .

[0668] To a solution of CP87-2 (4.11 g) in THF (50 mL) was added lithium aluminum hydride (633 mg), and the resulting mixture was stirred at 0° C. for 2 hours. The solution was diluted with THF (20 mL) and quenched with water (0.6 mL), 15% sodium hydroxide solution, and water (1.8 mL). The solution was filtered, concentrated, and purified to give CP87-3 (3506 mg). MS: m / z: 234 [M+H] + .

[0669] To a solution of CP87-3 (11.765 g) in DCM (120 mL) was added TEA (7.6541 g), TBDMSCl (7.6005 g), and DMAP (616.061 mg), and the resulting mixture was stirred at RT overnight. The mixture was diluted with DCM and worked up to give CP87-4 (12.691 g). MS: m / z: 348 [M+H] + .

[0670] To a solution of CP87-4 (8.557 g) in DCM (90 mL) was added trifluoroacetic acid (40 mL) at 0 °C, and the resulting mixture was stirred at RT for 3 h. The mixture was concentrated to give CP87-5 (22.433 g, crude product), which was carried on to the next step. MS: m / z: 134 [M+H] + .

[0671] Compound 87 (CP87, confirmed) was synthesized from CP87-5 by a method similar to that for CP47. MS: m / z: 630 [M+H] + .

[0672] Example 89 [ka]

[0673] A solution of 88-a (5.01 g), 2-methylpropane-2-sulfinamide (6.88 g), and tetraethyl titanate (18.91 g) in THF (150 mL) was stirred at 65 °C overnight. The reaction was concentrated to give CP88-1 (10.2 g), which was carried on to the next step. MS: m / z: 202 [M+H] + .

[0674] To a solution of CP88-1 (10.2 g) in MeOH (80 mL) was added NaBH4 (3.773 g) batchwise at 0°C, and the resulting mixture was stirred at the same temperature for 0.5 hours. The solution was quenched with water, and the white solid was filtered off. The filtered organic solution was concentrated, and the solution was extracted with EA. The organic layer was worked up to give CP88-2 (4.744 g). MS: m / z: 204 [M+H] + .

[0675] To a solution of CP88-2 (4.744 g) in DCM (50 mL) was added hydrochloric acid (15 mL). The solution was stirred at RT for 2 hours, and the reaction was concentrated. The residue was dissolved in MTBE and concentrated. MTBE was added to the residue at 0°C. The collected solid was filtered to give CP88-3 (1.784 g). MS: m / z: 100 [M+H] + .

[0676] CP88-5 was synthesized from CP88-3 by a method similar to that for INT15.

[0677] A solution of CP88-5 (593 mg), Grubbs second generation catalyst (103 mg), and acrylaldehyde dimethyl acetal (461 mg) in DCM (10 mL) was stirred at 45 °C under a N atmosphere for 16 h. The mixture was cooled to RT and concentrated. The resulting CP88-6 (453 mg) was purified. MS: m / z: 384 [M+H] + .

[0678] CP88-10 was synthesized from CP88-6 by a method similar to that for CP83-10.

[0679] CP88-10 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (20 mm x 250 mm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min, 220 nm. CP88-11 (second eluting isomer, retention time 6.053 min, 104 mg) was obtained. MS: m / z: 479 [M+H]+ .

[0680] Compound 88 (CP88, confirmed) was synthesized in CP88-11 by a method similar to that for CP46. MS: m / z: 628 [M+H] + .

[0681] Example 90 [ka]

[0682] CP89-d was synthesized using 89-a in a manner similar to that used for CP88-3.

[0683] At 0 °C, Cbz-Cl (3.545 g) was added dropwise to a solution of 89-d (2.327 g) and TEA (4.456 g) in DCM (50 mL). The solution was stirred at RT for 16 h under a N2 atmosphere. The mixture was diluted with NaCl solution, extracted with EA, and worked up to give 89-e (2.975 g). MS: m / z: 234 [M+H] + .

[0684] CP88-f was synthesized in a manner similar to that of CP88-6, CP89-e, and CP89-f.

[0685] To a solution of 89-f (3.364 g) in MeOH (150 mL) was added NaBH (0.743 g) dropwise at 0 °C. The solution was stirred at RT for 3 h under a N atmosphere. The mixture was quenched with water, extracted with EA, and worked up to give 89-g (3.14 g). MS: m / z: 264 [M+H] + .

[0686] A solution of 89-g (3.14 g) and Pd / C (604 mg) in THF (80 mL) was stirred at RT for 15 h under a H atmosphere. Mixing gave 89-h (1.565 g). MS: m / z: 132 [M+H] + .

[0687] To a solution of 89-h (1.565 g) and TEA (1.906 g) in THF (50 mL) was added Cbz-Cl (2.569 g) dropwise at 0 °C. The solution was stirred at RT for 15 h under a N2 atmosphere. The solution was filtered, and the filtrate was diluted with water and extracted with EA. After workup, 89-i (1.37 g) was obtained. MS: m / z: 266 [M+H] + .

[0688] A solution of 89-i (1.37 g) and Pd / C (1.63 g) in DCM (50 mL) was stirred at RT for 5 h under a N atmosphere. The solution was filtered, and the filtrate was concentrated and purified to give 89-j (893 mg). MS: m / z: 264 [M+H] + .

[0689] A solution of 89-j (893 mg), 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (2.541 g), and L-proline (85 mg) in ACN (15 ml) and methanol (15 ml) was stirred at 65 °C for 16 hours under a N atmosphere. The mixture was concentrated and purified to give 89-k (1.016 g). MS: m / z: 328 [M+H] + .

[0690] A solution of 89-k (1.016 g) and Pd / C (0.338 g) in THF (30 mL) was stirred at RT for 2 h under a H atmosphere. The mixture afforded 89-l (599.744 mg) as is. MS: m / z: 194 [M+H] + .

[0691] Compound 89 (CP89, confirmed) was synthesized in CP89-1 by a method similar to that for CP46. MS: m / z: 646 [M+1] + .

[0692] Example 91 [ka]

[0693] A solution of CP62-1 (2.64 g) in THF (200 mL) and DCM (100 mL) was added dropwise to DAST (1.69 g) under a N atmosphere at 0° C. and stirred at RT for 2 h. The solution was quenched with saturated NaHCO solution (100 mL), extracted with DCM (300 mL), dried, concentrated, and purified on a silica gel column (PE / EA=5 / 1) to give CP40A-1 (2.23 g).

[0694] CP40A-1 was separated by chiral high-performance liquid chromatography. Conditions: CHIRALPAK-IG, 20 mm x 250 mm, 5 μm, mobile phase: Hex (0.1% DEA) / EtOH (70:30), flow rate: 20 mL / min. CP40A-2 (first eluting isomer, retention time 6.3 min, 0.58 g) was obtained. MS: m / z: 372 [M+H] + .

[0695] Compound 40A (CP40A, confirmed) was synthesized from CP40A-2 by the procedure described in CP46 and purified by prep-HPLC (YMC-Triart C18-S12nm, 50mm x 250mm, 7µm, A: 0.05% NH₃·H₂O, B: CH₃CN, gradient: 36min, 35% B to 77% B, flow rate: 70mL / min, 2224nm). LCMS: m / z: 632 [M+H] + .

[0696] Example 92 [ka]

[0697] Compound 90 (CP90, confirmed) was synthesized by a method similar to that for CP46. MS: m / z: 656 [M+1] + .

[0698] Example 93 [ka]

[0699] [ka]

[0700] CP91-6 was synthesized by a method similar to that for CP71-6.

[0701] CP91-6 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, 20 mm x 250 mm, 5 μm; Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50); Flow rate: 15 mL / min, 220 nm. CP91-7A (41 mg, first eluting isomer, retention time 6.903 min) and CP91-7B (50 mg, second eluting isomer, retention time 7.681 min) were obtained. MS: m / z: 463 [M+1] + .

[0702] Compound 91A (CP91A, 26 mg, confirmed) was synthesized from CP91-7A by a method similar to the synthesis of CP46. MS: m / z: 612 [M+1] + .

[0703] Compound 91B (CP91B, 38 mg, confirmed) was synthesized from CP91-7B by a method similar to the synthesis of CP46. MS: m / z: 612 [M+1] + .

[0704] Example 94 [ka]

[0705] Benzyl bromide (57.81 g) was added dropwise to a solution of 92-a (9.9 g) and K2CO3 (47.17 g) in ethanol (300 mL) at 100 °C. The solution was stirred at 100 °C for 15 h under a N2 atmosphere. The mixture was concentrated, diluted with NaHCO3 solution, extracted with EA, and worked up to give CP92-1 (20.61 g). MS: m / z: 272 [M+H] + .

[0706] A solution of CP92-1 (20.61 g), DMAP (9.79 g), TEA (12.12 g), and TBDMSCl (13.82 g) in DCM (200 mL) was stirred at RT for 20 h. The solution was diluted with NaHCO3 solution and worked up to give CP92-2 (23.24 g). MS: m / z: 386 [M+H] + .

[0707] At 0°C, NaH (642 mg) was added to a solution of CP92-2 (4.15 g) in THF (50 mL). The solution was stirred under N2 atmosphere at 0°C for 10 minutes, and iodomethane (3.27 g) was added dropwise to the mixture. The solution was stirred under N2 atmosphere at RT for 16 hours. The solution was quenched with water, extracted with EA, and worked up to give CP92-3 (4.286 g). MS: m / z: 400 [M+H] + .

[0708] A solution of CP92-3 (4.286 g) and CsF (6.240 g) in DMF (40 mL) was stirred at 35 °C for 16 h. The solution was diluted with EA and washed with NaCl solution to give CP92-4 (2.518 g). MS: m / z: 286 [M+H] + .

[0709] CP92-11 was synthesized with CP92-4 by a method similar to that for CP46-10.

[0710] CP92-11 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, 20 mm x 250 mm, 5 μm; Mobile phase: (Hex:DCM=3:1) (0.1% DEA) / EtOH (50:50); Flow rate: 15 mL / min, 220 nm. CP92-12A (58 mg, first eluting isomer, retention time 6.797 min) and CP92-12B (26 mg, second eluting isomer, retention time 8.2 min) were obtained. MS: m / z: 497 [M+1] + .

[0711] Compound 92A (CP92A, 36.8 mg, assumed) was synthesized and purified from CP92-12A by a method similar to the synthesis of CP46. MS: m / z: 646 [M+1] + .

[0712] Compound 92B (CP92B, hypothetical) was synthesized from CP92-12B by a method similar to that used for the synthesis of CP46. MS: m / z: 646 [M+1] + .

[0713] Example 95 [ka]

[0714] Methylmagnesium bromide (8.5 mL) was added to a solution of CP61-1 (1.58 g) in THF (150 mL) at 0° C. The solution was stirred at 45° C. under a N atmosphere for 36 h. The mixture was quenched with NH4Cl solution, extracted with EA, and worked up to give CP93-1 (674 mg). MS: m / z: 384 [M+H] + .

[0715] A solution of CP93-1 (674 mg) and DAST (0.99 g) in DCM (10 mL) was stirred at 45 °C under a N atmosphere for 3 h. The mixture was cooled to RT and worked up by dilution with NaHCO solution to give CP93-2 (276 mg). MS: m / z: 386 [M+H] + .

[0716] CP93-4 was synthesized with CP93-2 by a method similar to that for CP46-10.

[0717] CP93-4 was separated by Prep-HPLC-Gilson under the following conditions: CHIRAL ART Cellulose-SC, 20 mm x 250 mm, 5 μm, mobile phase: (Hex:DCM=3:1) (0.1% DEA) / IPA (50:50), flow rate: 15 mL / min, 220 nm. CP93-5A (50 mg, first eluting isomer, retention time 4.933 min) and CP93-5B (49 mg, second eluting isomer, retention time 7.847 min) were obtained. MS: m / z: 497 [M+1] + .

[0718] Compound 93A (CP93A, 32.4 mg, confirmed) was synthesized from CP93-5A by a method similar to the synthesis of CP46. MS: m / z: 646 [M+1] + .

[0719] Compound 93B (CP93B, 32.7 mg, confirmed) was synthesized from CP93-5B by a method similar to the synthesis of CP46. MS: m / z: 646 [M+1] + .

[0720] Example 96 [ka]

[0721] To a solution of 94-a (10.09 g) in DCE (150 mL), benzylamine (22.87 g), and TEA (28.76 g) was added titanium tetrachloride (55.12 g) dissolved in DCM (50 mL), and the resulting mixture was stirred at 0 °C and then at RT for 5 h. At 0 °C, a solution of sodium cyanoborohydride (6.78 g) in MeOH (15 mL) was added. The solution was stirred at RT for 16 h. The mixture was adjusted to pH 8 with NaHCO3 (aq.). The mixture was worked up by diluting with EA and washing with water to give 94-b (4.86 g). MS: m / z: 236 [M+H] + .

[0722] To a solution of 94-b (4.50 g) in ACN (10 mL) were added K2CO3 (7.95 g), TBAl (0.85 g), and BnBr (6.69 g), and the resulting mixture was stirred at RT for 16 h. The solution was filtered and diluted with EA. The mixture was concentrated and purified to give 94-c (4.86 g). MS: m / z: 326 [M+H] + .

[0723] To a solution of 94-c (4.95 g) in THF (50 mL) was added LAH (1.22 g) at 0 °C, and the resulting mixture was stirred at 25 °C for 2 h. The mixture was then diluted with NaSO 10H O. The solution was filtered and diluted with EA. The mixture was concentrated and purified to give 94-d (4.48 g). MS: m / z: 284 [M+H] + .

[0724] To a solution of 94-d (4.48 g) in THF (50 mL) at 0 °C, NaH (1.61 g), DMAP (0.10 g), and TBAI (0.35 g) were added, and the resulting mixture was stirred at RT for 5 h at 70 °C. The solution was diluted with EA and worked up to give 94-e (5.01 g). MS: m / z: 372 [M+H] + .

[0725] To a solution of 94-e (2.06 g) in MeOH (20 ml) under a H atmosphere, Pd(OH) / C (0.44 g) and Pd / C (0.43 g) were added. The reaction mixture was stirred at 25 °C for 16 h. The resulting mixture was filtered, and the filtrate was concentrated to give CP94-1 (0.97 g, crude product). MS: m / z: 192 [M+H] + .

[0726] CP94-4 was synthesized with CP94-1 by a method similar to that for CP46-8.

[0727] CP94-4 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRALART Cellulose-SC, 20 mm x 250 mm, 5 μm; Mobile phase: (Hex:DCM=3:1) (0.1% DEA) / IPA (50:50); Flow rate: 17 mL / min, 220 nm. CP94-5A (first eluting isomer, retention time 4.728 min) and CP94-5 (second eluting isomer, retention time 10.189 min) were obtained. MS: m / z: 384 [M+H] + .

[0728] CP94 (CP94, confirmed) was synthesized from CP94-5 by the steps of CP46. LCMS: m / z: 644 [M+H] + .

[0729] Example 97 [ka]

[0730] To a solution of CP61-1 (2.16 g) in DCM (150 mL) and THF (150 mL) was added NaBD4 (0.75 g), and the resulting mixture was stirred at RT for 16 h. The solution was quenched with water, extracted with DCM, and worked up to give CP95-1 (1.93 g, crude product). MS: m / z: 371 [M+H] + .

[0731] CP95-4 was synthesized in a manner similar to that for CP40A-4, CP95-1.

[0732] CP95-4 was separated by Prep-HPLC-Gilson under the following conditions: CHIRAL ART Cellulose-SC, 20 mm x 250 mm, 5 μm, mobile phase: (Hex:DCM=3:1) (0.1% DEA) / IPA (50:50), flow rate: 15 mL / min. CP95-5 (second eluting isomer, retention time 7.580 min) was obtained.

[0733] Compound 95 (CP95, confirmed) was synthesized by the steps of CP93. LCMS: m / z: 633 [M+H] + .

[0734] Example 98 [ka]

[0735] A solution of 96-a (5.07 g), benzyl bromide (20.93 g), K2CO3 (16.70 g), and TBAI (10.5 g) in MeCN (100 mL) was stirred overnight at RT. The reaction solution was filtered, washed with EA, and concentrated. The residue was purified to give 96-b (1.38 g). MS: m / z: 286 [M+H] + .

[0736] To a solution of 96-b (6.32 g) in DCM (25 mL) and DMSO (50 mL) was added TEA (19.06 g) and pyridine sulfur trioxide (14.23 g), and the resulting mixture was stirred at 0 °C for 3 h. The reaction was quenched with NaSO, extracted with EA, and worked up to give 96-c (2.78 g). MS: m / z: 284 [M+H] + .

[0737] A mixture of 96-c (3.85 g), p-TsOH·HO (2.65 g), methyl orthoformate (4.36 g), and toluene (40 mL) was stirred at 100 °C for 16 h. The mixture was cooled to RT, diluted with EA, and worked up to give 96-d (2.35 g). MS: m / z: 330 [M+H] + .

[0738] To a solution of 96-d (2.35 g) in MeOH (20 ml) under a H atmosphere, Pd / C (0.43 g) was added. The reaction mixture was stirred at 25 °C for 16 h. The resulting mixture was filtered, and the filtrate was concentrated to give 96-e (873 mg). MS: m / z: 150 [M+H] + .

[0739] Compound 96 (CP96, confirmed) was synthesized using CP46 and CP96-e. LCMS: m / z: 628 [M+H] + .

[0740] Example 99 [ka]

[0741] A solution of 97-a (10.12 g), dibenzylamine (13.72 g), DMAP (1.82 g), and EDCI (23.62 g) in DCM (200 mL) was stirred overnight at RT. Quenched with NH4Cl, extracted with DCM, concentrated, and purified to give 97-b (14.09 g). MS: m / z: 324 [M+H] + .

[0742] A solution of 97-b (14.09 g) in BH3 / THF (120 mL) and THF (80 mL) was stirred at 60 °C for 16 h under a N2 atmosphere. MeOH (120 mL) was added to the reaction mixture, which was stirred at 60 °C for 30 min and concentrated. At 0 °C, THF (80 mL) and LAH (1.29 g) were added to the mixture, which was stirred at room temperature for 2 h. The reaction was quenched with Na2SO4·10H2O and worked up to give 97-c (9.44 g). MS: m / z: 282 [M+H] + .

[0743] Compound 97 (CP97, confirmed) was synthesized using CP97-c according to the procedure described in CP46. LCMS: m / z: 642 [M+H] + .

[0744] Example 100 [ka]

[0745] A solution of 98-a hydrochloride (10.32 g), TBAI (1.41 g), KCO (33.18 g), and BrBn (32.05 g) in MeCN (100 mL) was stirred at RT for 16 h. The mixture was concentrated and purified to give 98-b (17.2 g). MS: m / z: 284 [M+H] + .

[0746] To a solution of 98-b (17.2 g) in MeOH (40 mL) and HO (40 mL) was added sodium hydroxide. The reaction mixture was stirred at RT for 16 h, adjusted to pH 3, and concentrated. The mixture was quenched with water, extracted with EA, and worked up to give 98-c (12.3 g). MS: m / z: 270 [M+H] + .

[0747] To a solution of 98-c (12.3 g) in DMF (50 mL), dimethylhydroxylamine hydrochloride (5.96 g), HATU (20.85 g), and DIEA (20.54 g) were added. The reaction mixture was stirred at RT for 2 h. After completion, water was added, and the aqueous layer was extracted with EA. After workup, 98-d (13.95 g) was obtained. MS: m / z: 313 [M+H] + .

[0748] To a solution of 98-d (13.95 g) in THF (150 mL) was added MeMgBr (24.5 mL) at 0 °C. The mixture was stirred at RT for 8 h and quenched with aq. NH4Cl and water. The resulting mixture was extracted with DCM and worked up to give 98-e (5.8 g). MS: m / z: 268 [M+H] + .

[0749] To a solution of 98-e (5.8 g) in MeOH (50 mL) was added NaBH4 (1.24 g). The reaction mixture was stirred at RT for 1 h. The reaction mixture was concentrated. The mixture was quenched with water, extracted with EA, and worked up to give 98-f (5.75 g). MS: m / z: 270 [M+H] + .

[0750] CP98-2 was synthesized using CP98-f by the steps of CP46-8.

[0751] CP98-2 (3.12 g) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, 20 mm x 250 mm, 5 μm; Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50); Flow rate: 15 mL / min. CP98-3 (240 mg, third eluting isomer, retention time 9.080 min) was obtained.

[0752] Compound 98 (CP98) was synthesized from CP98-3 by the steps of CP46.

[0753] Compounds 98A (CP98A), 98B (CP98B), and 98C (CP98C) were synthesized in a similar manner. LCMS: m / z: 630 [M+H] + .

[0754] Example 101 [ka]

[0755] Compound 99 (CP99, confirmed) was synthesized in a similar manner to CP71. LCMS: m / z: 612 [M+H] + .

[0756] Example 102 [ka]

[0757] Compound 100 (CP100, confirmed) was synthesized from CP100-d by a method similar to the synthesis of CP94. LCMS: m / z: 686 [M+H] + .

[0758] Example 103 [ka]

[0759] [ka]

[0760] To a solution of CP61-1 (1.139 g) and p-toluenesulfonylmethyl isocyanide (0.876 g) in dioxane (40 mL) at 0° C., potassium tert-butoxide (0.415 g) was added. The mixture was stirred at 50° C. for 0.5 h and then at RT for 16 h. The reaction mixture was diluted with EA and worked up to give CP101-1 (587 mg). MS: m / z: 379 [M+H] + .

[0761] Compound 101 (CP101, confirmed) was synthesized from CP101-1 by a method similar to the preparation of CP46. LCMS: m / z: 639 [M+H] + .

[0762] Example 104 [ka]

[0763] CP46 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SA (2 cm x 25 cm, 5 μm), Mobile phase: Hex (0.1% DEA) / EtOH (50:50), Flow rate: 20 mL / min. Compound 102 (CP102, 17.5 mg, first eluting isomer, retention time 7.034 min) and Compound 103 (CP103, 5.7 mg, second eluting isomer, retention time 10.862 min) were obtained. MS: m / z: 630 [M+H] + .

[0764] Example 105 [ka]

[0765] CP9-3 (0.81 g), 3,3,3-trifluoropropylamine hydrochloride (0.85 g), DIEA (1.19 g), and DMA (10 mL) were added to a 48 mL sealed bottle to obtain a mixture, which was then stirred at 70 °C for 17 hours. The mixture was diluted with water, extracted with EA, and worked up to give CP104-1 (1.02 g). MS: m / z: 502 [M+H] + .

[0766] Compound 104 (CP104, confirmed) was synthesized from CP104-1 in a manner similar to the preparation of CP46. LCMS: m / z: 698 [M+H] + .

[0767] Example 106 [ka]

[0768] Compound 105 (CP105, confirmed) was synthesized from CP105-a in a manner similar to the preparation of CP94. LCMS: m / z: 670 [M+H] + .

[0769] Example 107 [ka]

[0770] To a solution of 106-a (19.93 g) in THF (200 mL) was added NaH (15.96 g) at 0 °C, and the resulting mixture was stirred at room temperature for 1 hour. Bromoacetaldehyde dimethyl acetal (6.29 g), benzyl bromide (35.67 g), and 4-dimethylaminopyridine (2.07 g) were added to the reaction mixture, and the resulting mixture was stirred at 25 °C for 16 hours under a N atmosphere. The mixture was quenched with water, extracted with EA, and worked up to give 106-b (34.24 g). MS: m / z: 191 [M+H] + .

[0771] A solution of 106-b (34.24 g) and m-chloroperoxybenzoic acid (40.60 g) in DCM (300 mL) was stirred at 25 °C for 16 h, quenched with NaSO, extracted with DCM, and worked up to give 106-c (20.94 g). MS: m / z: 207 [M+H] + .

[0772] A solution of 106-c (18.48 g) and dibenzylamine (53.47 g) in MeOH (300 mL) was stirred at 130 °C for 3 h. The mixture was cooled to RT, concentrated, and purified to give 106-d (34.63 g). MS: m / z: 404 [M+H] + .

[0773] To a solution of 106-d (32.46 g) and imidazole (21.97 g) in DMF (300 mL) was added tert-butyldimethylchlorosilane (36.70 g) at 0 °C, and the resulting mixture was stirred at 40 °C for 2 h. The mixture was diluted with EA and worked up to give 106-e (23.23 g). MS: m / z: 518 [M+H] + .

[0774] To a solution of 106-e (23.23 g) in methanol (300 mL) under a H atmosphere, Pd / C (11.78 g) and Pd(OH) / C (9.08 g) were added. The reaction mixture was stirred at 60 °C for 16 h, filtered, and concentrated to give 106-f (9.39 g). MS: m / z: 248 [M+H] + .

[0775] CP106-3 was synthesized in CP106-f by a method similar to that for CP40-8.

[0776] A solution of CP106-3 (2.47 g) and p-TsOH·HO (2.17 g) in DMSO (30 mL) was stirred at 80 °C for 16 h. The mixture was cooled to RT, quenched with water (50 mL), extracted with DCM, and worked up to give CP106-4 (337 mg). MS: m / z: 37 [M+H] + .

[0777] A solution of CP106-4 (0.337 g), triethylamine (792 mg), sulfur trioxide pyridine (610 mg), and DCM (3 mL) in DMSO (6 mL) was stirred at 25 °C for 16 h, quenched with NaSO, extracted with EA, and worked up to give CP106-5 (190 mg). MS: m / z: 368 [M+H] + .

[0778] To a solution of CP106-5 (0.19 g) in DCM (10 mL) at 0 °C, DAST (3.36 g) was added, and the resulting mixture was stirred at RT for 16 h, quenched with saturated aqueous NaHCO3, extracted with DCM, and worked up to give CP106-6 (132 mg). MS: m / z: 390 [M+H] + .

[0779] CP106-8 was synthesized from CP106-6 by a method similar to that for CP46-10.

[0780] CP106-8 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC (2 cm × 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min, 220 nm. CP106-9A (first eluting isomer, retention time 4.67 min) and CP106-9B (second eluting isomer, retention time 6.98 min) were obtained. LCMS: m / z: 650 [M+H] + .

[0781] Compound 106A (CP106A, confirmed) was synthesized from CP106-9A by a preparation method similar to that of CP46.

[0782] Compound 106B (CP106B, confirmed) was synthesized from CP106-9B by a similar preparation method to CP46. LCMS: m / z: 650 [M+H] + .

[0783] Example 108 [ka]

[0784] CP107-3 was synthesized in CP107-a by a method similar to that for CP94-4.

[0785] The crude product CP107-3 (0.95 g) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC (2 cm × 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min, 220 nm, CP107-4B (first eluting isomer, retention time: 4.17 min, 0.45 g) and CP107-4A (second eluting isomer, retention time: 7.193 min, 0.43 g) were obtained.

[0786] Compound 107A (CP107A, 57.4 mg, confirmed) was synthesized from CP107-4A by a method similar to that for CP46. MS: m / z: 658 [M+H] + .

[0787] Compound 107B (CP107B, 0.0708 g, confirmed) was synthesized from CP107-4B in a manner similar to that of CP46. MS: m / z: 658 [M+H] + .

[0788] Example 109 [ka]

[0789] CP108-2 was synthesized in INT17 by a method similar to that for CP46-10.

[0790] CP108-2 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min, 220 nm. CP108-3B (0.37 g, first eluting isomer, retention time 4.11 min) and CP108-3A (0.3 g, second eluting isomer, retention time 5.8 min) were obtained. MS: m / z: 479 [M+H] + .

[0791] CP108-4B was synthesized in a manner similar to that of CP46-11 using CP108-3B.

[0792] To a solution of CP108-4B (243.8000 mg) in THF (10 mL) was added DAST (0.41 g) at 0 °C under a N atmosphere, and the resulting mixture was stirred at RT for 2 h. The mixture was diluted with saturated NaHCO. Workup by extraction with EA gave CP108-5B (0.11 g). MS: m / z: 950 [M+H] + .

[0793] Compound 108B (CP108B, confirmed) was synthesized from CP108-5B in a manner similar to the preparation of CP46. LCMS: m / z: 630 [M+H] + .

[0794] Compound 108A (CP108A, confirmed) was synthesized from CP108-3A in a manner similar to the preparation of CP108B. LCMS: m / z: 630 [M+H] + .

[0795] Example 110 [ka]

[0796] A solution of CP10B-4 (140 mg) and CsF (0.35 g) in DMF (3 mL) was stirred at RT under a N atmosphere for 16 h. The solution was diluted with saturated aqueous NH4Cl and extracted with EA to give crude product CP109-1 (186 mg). MS: m / z: 780 [M+H] + .

[0797] A solution of crude product CP109-1 (186 mg) in THF (5 mL) was cooled to -30 °C under a N atmosphere, and LDA (2 M, 0.5 mL) was added dropwise at -30 °C. The mixture was stirred at -30 °C for 30 minutes, CD3OD (4 mL) was added at -30 °C, and the resulting mixture was stirred at -30 °C for 1 hour. DO and EA were added to the mixture, and workup gave crude product CP109-2 (0.19 g). MS: m / z: 781 [M+H] + .

[0798] To a solution of crude product CP109-2 (179 mg) in DCM (10 mL) was added TFA (2 mL). The mixture was stirred at RT for 1 h, diluted with 10% NaHCO3 solution, extracted with DCM, and worked up to give compound 109 (CP109, 74.3 mg, confirmed). 1 HNMR(400MHz,DMSO-d6)δ=7.80-7.67(m,1H),7.34-7.28(m,1H),7.03-6.98(m,2H ),5.59(s,2H),5.40-5.17(m,2H),4.55-4.38(m,1H),4.20-3.91(m,4H),3.62-3. 47(m,1H),3.46-3.22(m,2H),3.16-3.00(m,3H),3.02-2.92(m,3H),2.86-2.80(m ,1H),2.32-2.10(m,2H),2.08-1.95(m,3H),1.90-1.69(m,3H).MS:m / z:617[M+H] + .

[0799] Example 111 [ka]

[0800] To a solution of 108-3A (0.09 g) in CHOH (10 mL) and DCM (30 mL) was added Pd / C (0.0373 g). The mixture was stirred at RT under an H atmosphere for 3 h. The solution was filtered, and the filtrate was concentrated to give CP110-1 (0.0823 g). MS: m / z: 481 [M+H] + .

[0801] Compound 110 (CP110, confirmed) was synthesized from CP110-1 by a method similar to the preparation of CP46. LCMS: m / z: 630 [M+H] + .

[0802] Example 112 [ka]

[0803] Compound 111 (CP111, confirmed) was synthesized by a method similar to that for CP46. MS: m / z: 572 [M+H] + . 1 HNMR(400MHz,DMSO-d6)δ=7.80-7.68(m,1H),7.34-7.28(m,1H),7.05-6.95(m ,2H),5.58(s,2H),5.29-5.21(m,1H),4.53-4.31(m,2H),4.30-4.14(m,1.5H) ,4.05-3.88(m,2.5H),3.62-3.39(m,3H),3.08-2.93(m,4H),2.80-2.68(m,1H ),2.46-2.37(m,3H),2.35-2.18(m,2H),2.05-1.99(m,2H),1.78-1.60(m,3H).

[0804] Example 113 [ka]

[0805] A solution of CP108-5A (0.23 g) in 4 M HCl in dioxane (2 mL) in DCM (8 mL) was stirred at RT for 1 h. The solution was diluted with 10% NaHCO3 solution and extracted with DCM to give crude product CP112-1 (0.10 g) after workup. MS: m / z: 766 [M+H] + .

[0806] A solution of CP112-1 (0.1 g) and CsF (0.21 g) in DMF (5 mL) was stirred at RT for 2 h under a N atmosphere. The solution was diluted with saturated NaHCO solution. After extraction with EA and workup, compound 112 (CP112, 0.0034 g, confirmed). MS: m / z: 610 [M+H] + .

[0807] Example 114 [ka]

[0808] To a solution of CP78-1 (79 mg) in DCM (10 mL) was added m-CPBA (66 mg) at RT. The resulting mixture was stirred for 1 h, diluted with DCM, washed with aq. NaHCO3, and worked up to give CP113-1 (87 mg). MS (ESI, m / z): 478 [M+H] + .

[0809] To a solution of CP113-1 (87 mg) in 1,4-dioxane (5 mL), N,N-diisopropylethylamine (82 mg) and INT14 (69 mg) were added. The reaction mixture was stirred at 90 °C for 16 h, diluted with EA, and worked up to give CP113-2 (54 mg). MS (ESI, m / z): 573 [M+H] + .

[0810] A solution of CP113-2 (54 mg) in TFA (4 mL) was stirred at RT for 16 h and then concentrated. The residue was dissolved in EA, washed with aq. NaHCO, dried, concentrated and purified to give CP113-3 (33 mg). MS (ESI, m / z:): 453 [M+H] + .

[0811] Compound 113 (CP113, confirmed) (13.1 mg, TFA salt) was synthesized using CP113-3 by the method of CP46. MS (ESI, m / z:): 602 [M+H] + .

[0812] Example 115 [ka]

[0813] To a solution of 114-a (5.02 g) and tert-butyl acrylate (8.04 g) in 1,4-dioxane (25 mL), 60% KOH solution (aqueous, 1 mL) was added, and the resulting mixture was stirred at RT for 20 h, diluted with water, extracted with EA, and worked up to give 114-b (8.88 g). MS (ESI, m / z): 290 [M+H] + .

[0814] To a solution of 114-b (8.88 g) in THF (150 mL) was added LAH (1.70 g) batchwise at 0 °C. The resulting mixture was stirred at RT for 2 h and quenched sequentially with water, aq. 15% NaOH, and water. The mixture was filtered, and the filtrate was concentrated to give 114-c (6.29 g). MS (ESI, m / z): 220 [M+H] + .

[0815] To a solution of 114-c (5.946 g) in acetonitrile (60 mL) was added HCl (4 M in 1,4-dioxane, 20 mL). The reaction mixture was stirred at RT for 5 h and concentrated to give 114-d, which was used directly in the next step. MS (ESI, m / z): 120 [M+H] + .

[0816] Compound 114 (CP114, confirmed) was synthesized in 114-d by a method similar to CP96. MS (ESI, m / z): 616 [M+H] + .

[0817] Example 116 [ka]

[0818] To a solution of INT15 (619 mg) in (4-methoxyphenyl)methanol (5 mL) was added t-BuOK (60 mg). The resulting mixture was stirred at RT for 3 h and purified to give CP115-1 (0.36 g). MS: m / z: 504 [M+H] + .

[0819] A solution of CP115-1 (0.36 g) in TFA (3 mL) was stirred at RT for 4 h and concentrated to give CP115-2, which was directly used in the next step. MS: m / z: 384 [M+H] + .

[0820] To a solution of CP115-2 (442 mg) in THF (10 mL) and DCM (5 mL) was added NaBH4 (0.10 g) at 0 °C. The mixture was stirred overnight at RT, diluted with water and EA, and worked up to give CP115-3 (35 mg). MS: m / z: 386 [M+H] + .

[0821] To a solution of CP115-3 (35 mg) in DCM (5 mL) was added DAST (85 mg) at 0 °C. The mixture was stirred at RT for 2 h. The reaction mixture was diluted with saturated aqueous NaHCO3 and EA and worked up to give CP115-4 (9 mg). MS: m / z: 390 [M+H] + .

[0822] Compound 115 (CP115, free base, 2.3 mg, confirmed) was synthesized using CP115-4 by the method of CP46. LCMS: m / z: 650 [M+H] + .

[0823] Example 117 [ka]

[0824] Under a N2 atmosphere, trimethylsulfoxonium iodide (330 mg) was added batchwise to a solution of NaH (65 mg, 60% content) in DMSO (10 mL). The mixture was stirred at RT for 3 h. INT15 (0.5 g) was added batchwise, and the mixture was stirred at RT for 3.5 h. Dilution with water and EA and workup gave CP116-1 (279 mg). MS: m / z: 380 [M+H] + .

[0825] To a solution of CP116-1 (263 mg) in THF (6 mL) and DCM (3 mL) was added NaBH4 (70 mg). The mixture was stirred at RT overnight, diluted with water and EA, and worked up to give CP116-2 (284 mg). MS: m / z: 382 [M+H] + .

[0826] To a solution of CP116-2 (237 mg) in DCM (20 mL) was added DAST (511 mg) at 0° C. The mixture was stirred at RT for 1.5 h, diluted with DCM and water, and worked up to give CP116-3 (80 mg). MS: m / z: 384 [M+H] + .

[0827] CP116 (28.6 mg, free base, confirmed) was synthesized in a similar manner to CP46 using CP116-3. LCMS: m / z: 644 [M+H] + .

[0828] Example 118 [ka]

[0829] Compound 117 (CP117, confirmed) was synthesized by a method similar to that for CP9. LCMS: m / z: 624 [M+H] + .

[0830] Example 119 [ka]

[0831] To a solution of 118-a (6.21 g) and TEA (8.91 g) in DCM (40 mL) was added MsCl (3.96 g) dropwise at −10° C. The reaction mixture was stirred at −10° C. for 15 min, quenched with water, extracted with DCM, and worked up to give 118-b (8.35 g).

[0832] To a solution of 118-b (8.35 g) in DMF (50 mL) was added DIEA (11.38 g) and tert-butyl 2-methylhydrazinecarboxylate (4.69 g). The reaction mixture was stirred at 80 °C for 22 h, diluted with EA and water, and worked up to give 118-c (8.78 g). MS: m / z: 325 [M+H] + .

[0833] To a solution of 118-c (8.78 g) in MeOH (100 mL) was added Pd / C (2.27 g, 10% wt Pd content) and Pd(OH) / C (2.00 g, 7.6% wt Pd content). The reaction mixture was stirred under H atmosphere at RT for 19 h, filtered, and the filtrate was concentrated to give 118-d (5.84 g). MS: m / z: 235 [M+H] + .

[0834] To a solution of 118-d (1.51 g) in DCM (15 mL) was added TFA (6 mL). The reaction mixture was stirred at RT for 3 h and concentrated. The residue was dissolved in MeOH (30 mL), and the pH of the solution was adjusted to 13 with solid NaOH. After stirring for 2.5 h, the pH of the mixture was adjusted to 2 with HCl (4 M in dioxane). The reaction mixture was concentrated to give 118-e (crude product). MS: m / z: 135 [M+H] + .

[0835] Compound 118 (CP118, 2.6 mg, TFA salt, confirmed) was synthesized using the method of CP47. MS: m / z: 631 [M+H] + .

[0836] Example 120 [ka]

[0837] To a solution of CP36-9 (0.35 g) and 119-a (293 mg, synthesized according to the method described in WO2022042630) in toluene (20 mL) and water (5 mL), cataCxium A Pd G3 (66 mg) and Cs2CO3 (692 mg) were added. The reaction mixture was stirred at 100 °C under a N2 atmosphere for 20 hours, diluted with water, extracted with EA, and worked up to give compound 119 (CP119, 310 mg, confirmed). MS: m / z: 641 [M+H] + .

[0838] Example 121 [ka]

[0839] Compound 120 (CP120, confirmed) was synthesized in a similar manner to CP1 and CP119. LCMS: m / z: 640 [M+H] + .

[0840] Example 122 [ka]

[0841] To a solution of 121-a (2.06 g) in THF (80 mL) was added n-BuLi (17.6 mL, 2.5 mol / L hexane solution) dropwise at -5 °C. After stirring at -10 °C for 1.5 h, a solution of iodomethane (2.80 g) in THF (4 mL) was added dropwise at -5 °C, and the reaction mixture was stirred at 0 °C for 3 h and quenched with aq. NaHCO (50 mL, 10% wt). Workup by extraction with EA gave 121-b (2.24 g). MS: m / z: 128 [M+H] + .

[0842] To a mixture of 121-b (2.24 g) and water (40 mL) was added KOH (5.02 g). After stirring at 100 °C for 6.5 h, the reaction mixture was cooled to RT and (Boc)2O (4.61 g) was added. The reaction mixture was stirred at RT for 4 h, diluted with EA and water, and worked up to give 121-c (8.78 g). MS: m / z: 246 [M+H] + .

[0843] To a solution of 121-c (3.42 g) in THF (50 mL) was added LAH (1.21 g) batchwise at −10° C. The reaction mixture was stirred at RT for 2 h, quenched sequentially with water (1.5 mL), aq. NaOH (1.5 mL, 15% wt), and water (5 mL), filtered, and concentrated to give 121-d (1442 mg). MS: m / z: 232 [M+H] + .

[0844] To a solution of 121-d (1442 mg) in acetonitrile (20 mL) was added HCl (10 mL, 4 M in dioxane), stirred at RT for 1 h, and concentrated to give residue A.

[0845] To a mixture of INT6 (1.53 g) and DIEA (2.18 g) in toluene (15 mL) was added POCl3 (0.75 mL). The reaction mixture was stirred at 80 °C for 1 hour and concentrated to give residue B. The pH of a mixture of residue A in DCM (10 mL) was adjusted to basic with DIEA. To a mixture of residue B in DCM (20 mL) was added DIEA (3 mL) and the above mixture. The reaction mixture was stirred at RT for 2 hours, diluted with water, extracted with DCM, and worked up to give CP121-1 (3.03 g). MS: m / z: 393 [M+H] + .

[0846] Compound 121 (CP121, 44.3 mg, TFA salt, confirmed) was synthesized in CP121-1 by a method similar to that for CP47. MS: m / z: 628 [M+H] + .

[0847] Example 123 [ka]

[0848] To a solution of 122-a (5.06 g) in acetonitrile (100 mL) was added K2CO3 (22.73 g), tetrabutylammonium iodide (1.95 g), and benzyl bromide (23.89 g). The reaction mixture was stirred at RT for 20 h, filtered, concentrated, and purified to give 122-b (14.35 g). MS: m / z: 270 [M+H] + .

[0849] To a solution of 122-b (2.08 g) in THF (20 mL) was added NaH (0.81 g, 60% content in oil) at -10 °C. After stirring for 15 min, methyl 2-bromopropionate (1.56 g) was added to the mixture. The reaction mixture was stirred at RT for 2.5 h, quenched with water, extracted with EA, and worked up to give 122-c (2.26 g). MS: m / z: 356 [M+H] + .

[0850] To a solution of 122-c (2.26 g) in THF (30 mL) was added LAH (0.40 g) batchwise at −10° C. The reaction mixture was stirred at RT for 2 h and quenched with water (0.5 mL), aqueous NaOH (0.5 mL, 15% wt), and water (1.5 mL). The mixture was filtered, concentrated, and purified to give 122-d (1.94 g). MS: m / z: 328 [M+H] + .

[0851] To a solution of 122-d (1.94 g) in MeOH (30 mL) was added Pd / C (0.56 g, 10% wt Pd content) and Pd(OH) / C (0.53 g, 7.6 wt% Pd content). The reaction mixture was stirred under H atmosphere at RT for 21 h, filtered, and concentrated to give 122-e (0.65 g). MS: m / z: 148 [M+H] + .

[0852] Compound 122 (CP122, 7 mg, TFA salt, confirmed) was synthesized using CP122-e in a similar manner to CP47. MS: m / z: 644 [M+H] + .

[0853] Example 124 [ka]

[0854] CP123-5 was synthesized in CP123-a by a method similar to that for CP94-7.

[0855] The first peak of CP123-5 (64 mg) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SA, column (2 cm × 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 20 mL / min. CP123-5A (34 mg, first eluting isomer, retention time: 5.71 min) and CP123-5B (28 mg, second eluting isomer, retention time: 7.26 min) were obtained.

[0856] The second peak CP123-5 (70 mg) was separated by Prep-HPLC-Gilson under the following conditions: column: CHIRAL ART Cellulose-SC (2 cm × 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), flow rate: 15 mL / min, 220 nm. CP123-5C (23 mg, first eluting isomer, retention time: 6.897 min) and CP123-5D (19 mg, second eluting isomer, retention time: 14.551 min) were obtained.

[0857] [ka]

[0858] Compound 123B (CP123B, hypothetical) was synthesized from CP123-6B in a manner similar to that for CP46. MS: m / z: 658 [M+H] + .

[0859] [ka]

[0860] Compound 123A (CP123A, 7.8 mg, hypothetical) was synthesized from CP123-6A in a manner similar to that for CP123B. MS: m / z: 658 [M+H] + .

[0861] [ka]

[0862] Compound 123D (CP123D, 5.4 mg, hypothetical) was synthesized from CP123-6D in a manner similar to that for CP123B. MS: m / z: 658 [M+H] + .

[0863] [ka]

[0864] Compound 123C (CP123C, 6.6 mg, hypothetical) was synthesized from CP123-6C in a manner similar to that of CP123-6B. MS: m / z: 658 [M+H] + .

[0865] Example 125 [ka]

[0866] A solution of 124-a (3.00 g), dibenzylamine (25.03 g), and DBU (8.05 g) in acetonitrile (60 mL) was stirred at 50 °C for 20 h and then concentrated. The residue was dissolved in EA and washed with aq. NH4Cl to give 124-b (4243 mg). MS (ESI, m / z): 314 [M+H]. + .

[0867] To a solution of 124-b (4.908 g) in THF (90 mL), LAH (801 mg) was added batchwise, and the resulting mixture was stirred at RT for 2 h, quenched with water (0.8 mL), aq. 15% NaOH (0.8 mL), and water (2.4 mL), filtered, and concentrated to give 124-c (2540 mg). MS (ESI, m / z): 286 [M+H]. + .

[0868] To a stirred solution of 124-c (2.44 g) in THF (40 mL) under N2 atmosphere, NaH (1322 mg) was added, and the resulting mixture was stirred at RT for 30 min. 2-Bromo-1,1-dimethoxyethane (1537 mg), DMAP (113 mg), and tetrabutylammonium iodide (639 mg) were added, and the resulting mixture was stirred at 70 °C for 16 h. The resulting mixture was quenched with water, extracted with EA, and worked up to give 124-d (1.44 g). MS (ESI, m / z: 374 [M+H] + .

[0869] To a solution of 124-d (1.44 g) in methanol (40 mL) was added Pd / C (0.50 g) and Pd(OH) / C (0.46 g). The reaction mixture was stirred under H atmosphere at RT for 20 h, filtered, and concentrated to give 122-e (736 mg). MS (ESI, m / z:): 194 [M+H] + .

[0870] Compound 124 (CP124, 33.5 mg, TFA salt, confirmed) was synthesized from CP124-e in a similar manner to CP46. MS: [ESI, m / z:]: 648 [M+H] + .

[0871] Example 126 [ka]

[0872] Compound 125 (CP125, confirmed) was synthesized from CP125-a and CP9-6 by a method similar to that for CP71. MS: m / z: 610 [M+H]+ .

[0873] Example 127 [ka]

[0874] To a solution of CP124-3 (99 mg) in DCM (5 mL) was added MsCl (57 mg) and TEA (92 mg) at 0 °C. The resulting solution was stirred at RT for 3 h, diluted with DCM, washed with water, and worked up to give CP126-2 (116 mg). MS (ESI, m / z): 464 [M+H] + .

[0875] A solution of CP126-2 (116 mg), cesium fluoride (175 mg), and cyanotrimethylsilane (97 mg) in DMF (3 mL) was stirred at 80 °C under N2 for 17 h, diluted with EA, and washed with brine to give CP126-3 (60 mg). MS (ESI, m / z): 395 [M+H]. + .

[0876] Compound 126 (CP126, 12.1 mg, TFA salt, confirmed) was synthesized in CP126-3 by a method similar to that for CP46. MS (ESI, m / z): 655 [M+H] + .

[0877] Example 128 [ka]

[0878] A mixture of CP36 (50 mg) and Pd / C (136 mg) in methanol (10 mL) was stirred at RT under an atmosphere of H for approximately 3 hours, filtered, concentrated, and purified to give compound 127 (CP127, 55.6 mg, TFA salt, characterized). MS: m / z: 634 [M+1] + .

[0879] Example 129 [ka]

[0880] Compound 128 (CP128, 33.9 mg, TFA salt, confirmed) was synthesized in CP128-a by a method similar to that for CP12. MS: m / z: 627 [M+H] + .

[0881] Example 130 [ka]

[0882] To a solution of CP57 (53 mg) and acetic anhydride (23 mg) in DCM (4 mL) was added DMAP (3 mg). The reaction was stirred at RT under N2 for 1 h, diluted with brine, extracted with DCM, and worked up to give compound 129 (CP129, 63.3 mg, TFA salt, confirmed). MS: m / z: 690 [M+H] + .

[0883] Example 131 [ka]

[0884] To a solution of CP57 (69 mg) and N-Boc-L-valine (30 mg) in DMF (3 mL) was added HATU (111 mg) and DIEA (15 mg). The reaction was stirred overnight at RT under N2 atmosphere and then worked up by diluting with EA and washing twice with brine to give crude product CP130-2 (126 mg). MS: m / z: 847 [M+H] + .

[0885] A solution of CP130-2 (126 mg) in TFA (1 mL) and DCM (3 mL) was stirred at RT for 2 h and quenched with saturated NaHCO solution. Extraction with EA and workup gave compound 130 (CP130, 13.8 mg, TFA salt, confirmed). MS: m / z: 747 [M+H] + .

[0886] The following compounds were synthesized in a similar manner to the above compounds.

[0887] [Table 3]

[0888] [Table 4]

[0889] Example 150 [ka]

[0890] Compound 150 (CP150, confirmed) was synthesized by a method similar to that for CP46. MS: m / z: 630 [M+1] + .

[0891] Example 151 [ka]

[0892] Compound 151 (CP151, confirmed) was synthesized by a method similar to that for CP46. MS: m / z: 632 [M+1] + .

[0893] Example 152 [ka]

[0894] Compound 152 (CP152, confirmed) was synthesized by a method similar to that for CP46. MS: m / z: 615 [M+1] + .

[0895] Example 153 [ka]

[0896] Compound 153 (CP153, confirmed) was synthesized by a method similar to that for CP46. MS: m / z: 586 [M+H] + , 1 HNMR(400MHz,DMSO-d6)δ=7.74(dd,J=9.2,5.9Hz,1H),7.31(t,J=9.0Hz,1H),7.03-6.99(m,2H),5.59(s,2H),5.34(s,0.5H),5.21(s,0.5H),4.97-4 .91(m,1H),4.13-3.88(m,3H),3.81-3.61(m,2H),3.16-2.97(m,3H),2.89 (d,J=4.6Hz,3H),2.86-2.77(m,1H),2.25-1.93(m,7H),1.90-1.68(m,3H).

[0897] Example 154 [ka]

[0898] Compound 154 (CP154, confirmed) was synthesized by a method similar to that for CP46. MS: m / z: 507 [M+H] + .

[0899] Example 155 [ka]

[0900] CP155-6 (57 mg) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min. CP155-7A (19 mg, first eluting isomer, Retention time: 7.073 min) and CP155-7B (19 mg, second eluting isomer, Retention time: 11.157 min) were obtained.

[0901] Compound 155A (CP155A, confirmed, MS: m / z: 630 [M+H]) was obtained by a method similar to that for CP46. + ) and compound 155B (CP155B, MS: m / z: 630 [M+H] + ) was synthesized.

[0902] Example 156 [ka]

[0903] CP156-4 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM = 2:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min. CP156-5A (32 mg, first eluting isomer, retention time: 4.877 min) and CP156-5B (37 mg, second eluting isomer, retention time: 5.813 min) were obtained.

[0904] Intermediate CP156-4 (another peak) was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM = 2:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min. CP156-5C (26 mg, first eluting isomer, Retention time: 5.193 min) and CP156-5D (27 mg, second eluting isomer, Retention time: 9.827 min) were obtained.

[0905] Compound 156A (CP156A, hypothetical, MS: m / z: 646 [M+H]) was isolated by a method similar to that for CP46. + ), compound 156B (CP156B, assumed, MS:m / z:646[M+H] + ), compound 156C (CP156C, assumed, MS:m / z:646[M+H] + ), and compound 156D (CP156D, hypothetical, MS: m / z: 646 [M+H]+) were synthesized.

[0906] Example 157 [ka]

[0907] CP157-4 was separated by Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SC, column (2 cm x 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 15 mL / min. CP157-5A (38 mg, first eluting isomer, Retention time: 7.631 min) and CP157-5B (39 mg, second eluting isomer, Retention time: 9.974 min) were obtained.

[0908] Compound 157A (CP157A, confirmed, MS: m / z: 628 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0909] Compound 138 (CP138, confirmed, MS: m / z: 628 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0910] Example 158 [ka]

[0911] Compound 158 (CP158, confirmed, MS: m / z: 671 [M+H]) was obtained by a method similar to that for CP1. + ) was synthesized. Separation was performed using Prep-HPLC-Gilson under the following conditions: Column: CHIRAL ART Cellulose-SB (2 cm × 25 cm, 5 μm), Mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), Flow rate: 20 mL / min. Compound 158A (first eluting isomer, retention time 3.705 min) and Compound 158B (second eluting isomer, retention time 4.773 min) were obtained.

[0912] Example 159 [ka]

[0913] Compound 159A (CP159A, hypothetical, MS: m / z: 628 [M+H]) was isolated by a method similar to that for CP46. + ) and compound 159B (CP159B, hypothetical, MS: m / z: 628 [M+H] + ) was synthesized.

[0914] Example 160 [ka]

[0915] Compound 160 (CP160, confirmed, MS: m / z: 624 [M+H]) was obtained by a method similar to that for CP1. + ) was synthesized.

[0916] Example 161 [ka]

[0917] Compound 161 (CP161, confirmed, MS: m / z: 623 [M+H]) was obtained by a method similar to that for CP11. + ) was synthesized.

[0918] Example 162 [ka]

[0919] Compound 162 (CP162, confirmed, MS: m / z: 616 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0920] Example 163 [ka]

[0921] Compound 163 (CP163) was synthesized and separated using a method similar to that for CP66 under the following conditions: Column: CHIRAL ART Amylose-SA, column (2 cm x 25 cm, 5 μm), mobile phase: (Hex:DCM = 3:1) (0.1% DEA) / EtOH (50:50), flow rate: 20 mL / min. Compound 163A (CP163A, confirmed, first eluting isomer, retention time 3.877 min) and compound 163B (CP163B, confirmed, second eluting isomer, retention time 5.047 min) were obtained. MS: m / z: 641 [M+H] + .

[0922] Example 164 [ka]

[0923] Compound 164 (CP164, confirmed, MS: m / z: 629 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0924] Example 165 [ka]

[0925] Compound 165 (CP165, confirmed, MS: m / z: 664 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0926] Example 166 [ka]

[0927] Compound 166 (CP166, confirmed, MS: m / z: 639 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0928] Example 167 [ka]

[0929] Compound 167 (CP167, confirmed, MS: m / z: 644 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0930] Example 168 [ka]

[0931] Compound 168B (CP168B, confirmed, MS: m / z: 639 [M+H]) was isolated by a method similar to that for CP46. + ) was synthesized.

[0932] Example 169 [ka]

[0933] Compound 169 (CP169, confirmed, MS: m / z: 640 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0934] Example 170 [ka]

[0935] Compound 170 (CP170, confirmed, MS: m / z: 640 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0936] Example 171 [ka]

[0937] Compound 171 (CP171, confirmed, MS: m / z: 628 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0938] Example 172 [ka]

[0939] Compound 172 (CP172, confirmed, MS: m / z: 641 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0940] Example 173 [ka]

[0941] Compound 173 (CP173, confirmed, MS: m / z: 628 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0942] Example 174 [ka]

[0943] Compound 174 (CP174, confirmed, MS: m / z: 646 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0944] Example 175 [ka]

[0945] Compound 175 (CP175, confirmed, MS: m / z: 628 [M+H]) was obtained by a method similar to that for CP46. + ) was synthesized.

[0946] Example 176 [ka]

[0947] Compound 176 (CP176) was synthesized by a method similar to that for CP66 and separated by prep-HPLC (Agela Durashell C18, 30 mm x 250 mm, 10 μm, A: 0.05% NH₃·H₂O, B: CH₃CN, gradient: 39 min, 30% B to 74% B, flow rate: 40 mL / min, 240 nm). Compound 176A (CP176A) (1.2 mg, TFA salt, confirmed) and compound 176B (CP176B, compound 139, confirmed) (1.0 mg) were obtained. MS: m / z: 655 [M+H] + .

[0948] Example 177 [ka]

[0949] Compound 177 (CP177) was synthesized using CP50 and an acid anhydride or acyl chloride. Compound 177 is a prodrug of CP50. It was observed that compound 177 was converted to the active component of CP50 in vivo. Exemplary Compounds 1 The HNMR is shown in the table below:

[0950] [Table 5]

[0951] [Table 6]

[0952] [Table 7]

[0953] [Table 8]

[0954] [Table 9]

[0955] Pharmacological testing 1. SOS1-catalyzed nucleotide exchange assay The inhibitory activity of various compounds against the GDP form of K-Ras was evaluated in an SOS1-catalyzed nucleotide exchange assay using K-Ras G12D and K-Ras G12V proteins.

[0956] In a 384-well plate (Greiner), GDP-preloaded K-Ras (His tag, aa 1-169) was preincubated with various compounds in the presence of 10 nM GDP for 15 minutes, followed by incubation with purified SOS1 ExD (Flag tag, aa 564-1049), BODIPY, or ATP. TM FL GTP (Invitrogen) and monoclonal antibody anti-6HIS-Tb cryptate Gold (Cisbio) were added to the assay wells and incubated at 25°C for 4 hours. The final concentrations of each component in the assay wells are shown in Table 1. Wells containing the same percentage of DMSO served as solvent controls, and wells without K-Ras served as negative controls. TR-FRET signals were read using a Tecan Spark multimode microplate reader. The parameters were as follows: F486: excitation 340 nm, emission 486 nm, delay time 100 μs, integration time 200 μs; F515: excitation 340 nm, emission 515 nm, delay time 100 μs, integration time 200 μs. The TR-FRET ratio for each well was calculated using the following formula: TR-FRET ratio = (F515 signal / F486 signal) × 10,000. The percentage activation of wells after compound treatment was normalized between the solvent control and the negative control (% activation = (TR-FRET ratio 化合物処理 -TR-FRET ratio 陰性対照) / (TR‐FRET ratio 溶媒対照 -TR-FRET ratio 陰性対照 ) × 100%). Data were analyzed using a 4-parameter logarithmic model or Excel to determine IC 50 The values ​​were calculated and the results are shown in Table 3 below.

[0957] [Table 10]

[0958] 2. Interaction test between GTP-K-Ras and cRAF The inhibitory activity of various compounds against the GTP form of K-Ras was evaluated by measuring the interaction between GppNp-K-Ras and cRAF. GppNp is a GTP analog. K-Ras G12D and K-Ras G12V proteins were used in this assay.

[0959] In a 384-well plate (Greiner), GppNp-preloaded K-Ras (His tag, aa 1-169) was preincubated with various compounds in the presence of 200 μM GTP for 15 minutes. Then, cRAF RBD (GST tag, aa 50-132, CreativeBioMart), monoclonal antibody GST-d2 (Cisbio), and monoclonal antibody anti-6HIS-Tb cryptate Gold (Cisbio) were added to the assay wells and incubated at 25°C for 2 hours. The final concentrations of each component in the assay wells are shown in Table 2. Wells containing the same percentage of DMSO served as solvent controls, and wells without K-Ras served as negative controls. HTRF signals were read using a Tecan Spark multimode microplate reader, and HTRF ratios were calculated according to the manufacturer's instructions. The activation percentages of compound-treated wells were normalized between the solvent control and the negative control (% activation = (HTRF ratio)). 化合物処理 -HTRF ratio 陰性対照 ) / (HTRF ratio 溶媒対照 -HTRF ratio 陰性対照 ) × 100%). Data were analyzed using a 4-parameter logarithmic model or Excel to determine IC50 The values ​​were calculated and the results are shown in Table 3 below.

[0960] [Table 11]

[0961] [Table 12]

[0962] [Table 13]

[0963] [Table 14]

[0964] [Table 15]

[0965] [Table 16]

[0966] [Table 17]

[0967] 3. Phosphorylation-ERK1 / 2 (Thr202 / Tyr204) HTRF assay The p-ERK (MAPK pathway) inhibitory activity of various compounds was evaluated in the K-Ras G12D and K-Ras G12V cell lines shown in Table 4.

[0968] [Table 18]

[0969] Cells in culture medium were seeded into 96-well plates at the densities shown in Table 4 and cultured overnight in a cell incubator. The next day, the medium was removed, and compounds diluted in test medium were added to each well. After 2 hours of incubation in the cell incubator, the test medium was removed from the 96-well plate, and 50 μL of lysis buffer (Cisbio) supplemented with 1X blocking reagent was added. The plate was incubated at 25°C for 45 minutes with shaking. 10 μL of cell lysate from the 96-well plate was transferred to a 384-well plate (Greiner) containing 2.5 μL / well of HTRF® premixed antibody (Cisbio 64AERPEH). The plate was incubated at 25°C for 4 hours, and the HTRF signal was read using a Tecan Spark multimode microplate reader. The IC was calculated using a 4-parameter logarithmic model. 50 The values ​​were calculated and the results are shown in Table 5 below.

[0970] [Table 19]

[0971] [Table 20]

[0972] [Table 21]

[0973] [Table 22]

[0974] 4. Cytoinhibition Measurement The K-Ras G12D and K-Ras G12V cell lines shown in Table 6 were used to perform cell growth inhibition assays, and the cell growth inhibition activities of various compounds were measured.

[0975] [Table 23]

[0976] 2D cell growth inhibition analysis After TC treatment, various cells in culture medium were seeded into the 96-well plate at the densities shown in Table 6 and cultured overnight in a cell incubator. The following day, various compounds were diluted with culture medium and added to the plate. After 6 days of incubation in the cell incubator, cell activity was measured using the CellTiter-Glo® Cell Activity Assay Kit (Promega). Luminescence signals were read using a Tecan Spark multimode microplate reader and analyzed using a 4-parameter logarithmic model to determine absolute IC values. 50 The values ​​were calculated and the results are shown in Table 7 below.

[0977] [Table 24]

[0978] [Table 25]

[0979] [Table 26]

[0980] 5. Mouse Pharmacokinetics Study This study aimed to evaluate the pharmacokinetic properties of compounds after single-dose administration in female Balb / c mice. Six mice were required for each compound, and the six mice were divided into two groups (n = 3 per group): Group A and Group B. Mice in Group A were treated with a single 3 mg / kg dose of compound (iv). Mice in Group B were treated with a single 10 mg / kg dose of compound (po). Blood samples were collected from each mouse in Group A at 0.083 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 h post-dose. Blood samples were collected from each mouse in Group B at 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 h post-dose. Blood samples were kept on ice until centrifugation to obtain plasma samples. Plasma samples were stored at -80°C until analysis. Compound concentrations in plasma samples were measured using LC-MS / MS. The results are shown in Table 8.

[0981] [Table 27]

Claims

1. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, 【Chemistry 1】 where: X １ is, in each occurrence, independently a bond, —C(R Ｘ１１ ) (R Ｘ１２ ) -, -NR Ｘ１３ -, -O-, -S-, -S(=O)-, or -S(=O) ２ - and R Ｘ１１ or R Ｘ１２ are independently hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —N(R Ａ ) ２ , -OR Ａ , -SR Ａ , -S(=O)R Ｂ , -S(=O) ２ R Ｂ , -C(=O)R Ｂ , -C(=O)OR Ｂ , -C(=O)N(R Ｂ ) ２ , -S(=O)OR Ｂ , -S(=O)N(R Ｂ ) ２ , -S(=O) ２ OR Ｂ , -S(=O) ２ N (R Ｂ ) ２ , -P(=O)(R Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl groups, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｃ ) ２ , -OR Ｃ , -SR Ｃ , -S(=O)R Ｄ , -S(=O) ２ R Ｄ , -C(=O)R Ｄ , -C(=O)OR Ｃ , —OC(═O)R Ｄ , -C(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)R Ｄ , -OC(=O)OR Ｃ , -NR Ｃ C(=O)OR Ｄ , -OC(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)N(R Ｃ ) ２ , -S(=O)OR Ｃ , -OS(=O)R Ｄ , -S(=O)N(R Ｃ ) ２ , -NR Ｃ S(=O)R Ｄ , -S(=O) ２ OR Ｃ , -OS(=O) ２ R Ｄ , -S(=O) ２ N (R Ｃ ) ２ , -NR Ｃ S (= O) ２ R Ｄ , -OS(=O) ２ OR Ｃ , -NR Ｃ S (= O) ２ OR Ｃ , -OS(=O) ２ NR Ｃ , -NR Ｃ S (= O) ２ N (R Ｃ ) ２ , -P(R Ｃ ) ２ , -P(=O)(R Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, R Ｘ１１ and R Ｘ１２ together with the carbon atoms bonded to both of these, 【Chemistry 2】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Transformation 3】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R ＳＸ１ is replaced by R Ｘ１３ is hydrogen, deuterium, -C １－６ Alkyl group, halogenated C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —S(═O)R Ｂ , -S(=O) ２ R Ｂ , -C(=O)R Ｂ , -C(=O)OR Ｂ , -C(=O)N(R Ｂ ) ２ , -S(=O)OR Ｂ , -S(=O)N(R Ｂ ) ２ , -S(=O) ２ OR Ｂ , -S(=O) ２ N (R Ｂ ) ２ , -P(=O)(R Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｃ ) ２ , -OR Ｃ , -SR Ｃ , -S(=O)R Ｄ , -S(=O) ２ R Ｄ , -C(=O)R Ｄ , -C(=O)OR Ｃ , —OC(═O)R Ｄ , -C(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)R Ｄ , -OC(=O)OR Ｃ , -NR Ｃ C(=O)OR Ｄ , -OC(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)N(R Ｃ ) ２ , -S(=O)OR Ｃ , -OS(=O)R Ｄ , -S(=O)N(R Ｃ ) ２ , -NR Ｃ S(=O)R Ｄ , -S(=O) ２ OR Ｃ , -OS(=O) ２ R Ｄ , -S(=O) ２ N (R Ｃ ) ２ , -NR Ｃ S (= O) ２ R Ｄ , -OS(=O) ２ OR Ｃ , -NR Ｃ S (= O) ２ OR Ｃ , -OS(=O) ２ NR Ｃ , -NR Ｃ S (= O) ２ N (R Ｃ ) ２ , -P(R Ｃ ) ２ , -P(=O)(R Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; X ２ is, at each occurrence, independently N or CR １ and R １ is hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R １Ａ ) ２ , -OR １Ａ , -SR １Ａ , -S(=O)R １Ｂ , -S(=O) ２ R １Ｂ , -C(=O)R １Ｂ , -C(=O)OR １Ａ , —OC(═O)R １Ｂ , -C(=O)N(R １Ａ ) ２ , -NR １Ａ C(=O)R １Ｂ , -OC(=O)OR １Ａ , -NR １Ａ C(=O)OR １Ａ , -NR １Ａ C(=S) OR １Ａ , -OC(=O)N(R １Ａ ) ２ , -NR １Ａ C(=O)N(R １Ａ ) ２ , -S(=O)OR １Ａ , -OS(=O)R １Ｂ , -S(=O)N(R １Ａ ) ２ , -NR １Ａ S(=O)R １Ｂ , -S(=O) ２ OR １Ａ , -OS(=O) ２ R １Ｂ , -S(=O) ２ N (R １Ａ ) ２ , -NR １Ａ S (= O) ２ R １Ｂ , -OS(=O) ２ OR １Ａ , -NR １Ａ S (= O) ２ OR １Ａ , -OS(=O) ２ N (R １Ａ ) ２ , -NR １Ａ S (= O) ２ N (R １Ａ ) ２ , -P(R １Ａ ) ２ , -P(=O)(R １Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R １Ｃ ) ２ , -OR １Ｃ , -SR １Ｃ , -S(=O)R １Ｄ , -S(=O) ２ R １Ｄ , -C(=O)R １Ｄ , -C(=O)OR １Ｄ , —OC(═O)R １Ｄ , -C(=O)N(R １Ｃ ) ２ , -NR １Ｃ C(=O)R １Ｄ , -OC(=O)OR １Ｃ , -NR １Ｃ C(=O)OR １Ｃ , -NR １Ｃ C(=S) OR １Ｃ , -OC(=O)N(R １Ｃ ) ２ , -NR １Ｃ C(=O)N(R １Ｃ ) ２ , -S(=O)OR １Ｃ , -OS(=O)R １Ｄ , -S(=O)N(R １Ｃ ) ２ , -NR １Ｃ S(=O)R １Ｄ , -S(=O) ２ OR １Ｃ , -OS(=O) ２ R １Ｄ , -S(=O) ２ N (R １Ｃ ) ２ , -NR １Ｃ S (= O) ２ R １Ｄ , -OS(=O) ２ OR １Ｃ , -NR １Ｃ S (= O) ２ OR １Ｃ , -OS(=O) ２ N (R １Ｃ ) ２ , -NR １Ｃ S (= O) ２ N (R １Ｃ ) ２ , -P(R １Ｃ ) ２ , -P(=O)(R １Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; n １ is 0, 1, 2, 3, 4, 5, or 6, Ring A is a 3- to 20-membered heterocycle containing only N atoms bonded to the pyrimidine ring, or O, S, S=O, and S(=O) in addition to the N atom bonded to the pyrimidine ring. ２ is a 3- to 20-membered (e.g., 3- to 10-membered) heterocycle further containing one or more heteroatoms selected from R Ｓ１ are independently hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ１Ａ ) ２ , -OR Ｓ１Ａ , -SR Ｓ１Ａ , -S(=O)R Ｓ１Ｂ , -S(=O) ２ R Ｓ１Ｂ , -C(=O)R Ｓ１Ｂ , -C(=O)OR Ｓ１Ａ , —OC(═O)R Ｓ１Ｂ , -C(=O)N(R Ｓ１Ａ ) ２ , -N Ｓ１Ａ C(=O)R Ｓ１Ｂ , -OC(=O)OR Ｓ１Ａ , -N Ｓ１Ａ C(=O)OR Ｓ１Ａ , -NR Ｓ１Ａ C(=S)O Ｓ１Ａ , -OC(=O)N(R Ｓ１Ａ ) ２ , -NR Ｓ１Ａ C(=O)N(R Ｓ１Ａ ) ２ , -S(=O)OR Ｓ１Ａ , -OS(=O)R Ｓ１Ｂ , -S(=O)N(R Ｓ１Ａ ) ２ , -NR Ｓ１Ａ S(=O)R Ｓ１Ｂ , -S(=O) ２ OR Ｓ１Ａ , -OS(=O) ２ R Ｓ１Ｂ , -S(=O) ２ N (R Ｓ１Ａ ) ２ , -NR Ｓ１Ａ S (= O) ２ R Ｓ１Ｂ , -OS(=O) ２ OR Ｓ１Ａ , -NR Ｓ１Ａ S (= O) ２ OR Ｓ１Ａ , -OS(=O) ２ N (R Ｓ１Ａ ) ２ , -NR Ｓ１Ａ S (= O) ２ N (R Ｓ１Ａ ) ２ , -P(R Ｓ１Ａ ) ２ , -P(=O)(R Ｓ１Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ１Ｃ ) ２ , -OR Ｓ１Ｃ , -SR Ｓ１Ｃ , -S(=O)R Ｓ１Ｄ , -S(=O) ２ R Ｓ１Ｄ , -C(=O)R Ｓ１Ｄ , -C(=O)OR Ｓ１Ｃ , —OC(═O)R Ｓ１Ｄ , -C(=O)N(R Ｓ１Ｃ ) ２ , -NR Ｓ１Ｃ C(=O)R Ｓ１Ｄ , -OC(=O)OR Ｓ１Ｃ , -NR Ｓ１Ｃ C(=O)OR Ｓ１Ｃ , -NR Ｓ１Ｃ C(=S) OR Ｓ１Ｃ , -OC(=O)N(R Ｓ１Ｃ ) ２ , -NR Ｓ１Ｃ C(=O)N(R Ｓ１Ｃ ) ２ , -S(=O)OR Ｓ１Ｃ , -OS(=O)R Ｓ１Ｄ , -S(=O)N(R Ｓ１Ｃ ) ２ , -NR Ｓ１Ｃ S(=O)R Ｓ１Ｄ , -S(=O) ２ OR Ｓ１Ｃ , -OS(=O) ２ R Ｓ１Ｄ , -S(=O) ２ N (R Ｓ１Ｃ ) ２ , -NR Ｓ１Ｃ S (= O) ２ R Ｓ１Ｄ , -OS(=O) ２ OR Ｓ１Ｃ , -NR Ｓ１Ｃ S (= O) ２ OR Ｓ１Ｃ , -OS(=O) ２ N (R Ｓ１Ｃ ) ２ , -NR Ｓ１Ｃ S (= O) ２ N (R Ｓ１Ｃ ) ２ , -P(R Ｓ１Ｃ ) ２ , -P(=O)(R Ｓ１Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R Ｓ１ together with the carbon atoms bonded to both of these, 【Chemistry 4】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Transformation 5】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ１１ is replaced by Optionally, two adjacent R Ｓ１ along with the atoms to which they are bonded, 【Transformation 6】 and forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R Ｓ１２ is replaced by Optionally, two non-adjacent R Ｓ１ are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or selected from the group consisting of N, O, S, S=O, and S(=O). ２ and the hydrogen on each carbon or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R Ｓ１３ is replaced by m １ is 0, 1, 2, 3, 4, 5, 6, 7, 8, or 9, R Ｓ２ are independently hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ２Ａ ) ２ , -OR Ｓ２Ａ , -SR Ｓ２Ａ , -S(=O)R Ｓ２Ｂ , -S(=O) ２ R Ｓ２Ｂ , -C(=O)R Ｓ２Ｂ , -C(=O)OR Ｓ２Ａ , —OC(═O)R Ｓ２Ｂ , -C(=O)N(R Ｓ２Ａ ) ２ , -NR Ｓ２Ａ C(=O)R Ｓ２Ｂ , -OC(=O)OR Ｓ２Ａ , -NR Ｓ２Ａ C(=O)OR Ｓ２Ａ , -NR Ｓ２Ａ C(=S) OR Ｓ２Ａ , -OC(=O)N(R Ｓ２Ａ ) ２ , -NR Ｓ２Ａ C(=O)N(R Ｓ２Ａ ) ２ , -S(=O)OR Ｓ２Ａ , -OS(=O)R Ｓ２Ｂ , -S(=O)N(R Ｓ２Ａ ) ２ , -NR Ｓ２Ａ S(=O)R Ｓ２Ｂ , -S(=O) ２ OR Ｓ２Ａ , -OS(=O) ２ R Ｓ２Ｂ , -S(=O) ２ N (R Ｓ２Ａ ) ２ , -NR Ｓ２Ａ S (= O) ２ R Ｓ２Ｂ , -OS(=O) ２ OR Ｓ２Ａ , -NR Ｓ２Ａ S (= O) ２ OR Ｓ２Ａ , -OS(=O) ２ N (R Ｓ２Ａ ) ２ , -NR Ｓ２Ａ S (= O) ２ N (R Ｓ２Ａ ) ２ , -P(R Ｓ２Ａ ) ２ , -P(=O)(R Ｓ２Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ２Ｃ ) ２ , -OR Ｓ２Ｃ , -SR Ｓ２Ｃ , -S(=O)R Ｓ２Ｄ , -S(=O) ２ R Ｓ２Ｄ , -C(=O)R Ｓ２Ｄ , -C(=O)OR Ｓ２Ｄ , —OC(═O)R Ｓ２Ｄ , -C(=O)N(R Ｓ２Ｃ ) ２ , -NR Ｓ２Ｃ C(=O)R Ｓ２Ｄ , -OC(=O)OR Ｓ２Ｃ , -NR Ｓ２Ｃ C(=O)OR Ｓ２Ｃ , -NR Ｓ２Ｃ C(=S) OR Ｓ２Ｃ , -OC(=O)N(R Ｓ２Ｃ ) ２ , -NR Ｓ２Ｃ C(=O)N(R Ｓ２Ｃ ) ２ , -S(=O)OR Ｓ２Ｃ , -OS(=O)R Ｓ２Ｄ , -S(=O)N(R Ｓ２Ｃ ) ２ , -NR Ｓ２Ｃ S(=O)R Ｓ２Ｄ , -S(=O) ２ OR Ｓ２Ｃ , -OS(=O) ２ R Ｓ２Ｄ , -S(=O) ２ N (R Ｓ２Ｃ ) ２ , -NR Ｓ２Ｃ S (= O) ２ R Ｓ２Ｄ , -OS(=O) ２ OR Ｓ２Ｃ , -NR Ｓ２Ｃ S (= O) ２ OR Ｓ２Ｃ , -OS(=O) ２ N (R Ｓ２Ｃ ) ２ , -NR Ｓ２Ｃ S (= O) ２ N (R Ｓ２Ｃ ) ２ , -P(R Ｓ２Ｃ ) ２ , -P(=O)(R Ｓ２Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R Ｓ２ together with the carbon atoms bonded to both of these, 【Transformation 7】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Transformation 8】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ２１ is replaced by Optionally, two adjacent R Ｓ２ along with the atoms to which they are bonded, 【Chemistry 9】 and forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R Ｓ２２ is replaced by Optionally, two non-adjacent R Ｓ２ are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or selected from the group consisting of N, O, S, S=O, and S(=O). ２ and the hydrogen on each carbon or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R Ｓ２３ is replaced by m ２ is 0, 1, 2, 3, 4, or 5, Y １ is a bond, O, S, S(=O), S(=O) ２ , or NR Ｙ１１ and R Ｙ１１ is hydrogen, deuterium, -C １－６ Alkyl group, halogenated C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —S(═O)R Ｂ , -S(=O) ２ R Ｂ , -C(=O)R Ｂ , -C(=O)OR Ｂ , -C(=O)N(R Ｂ ) ２ , -S(=O)OR Ｂ , -S(=O)N(R Ｂ ) ２ , -S(=O) ２ OR Ｂ , -S(=O) ２ N (R Ｂ ) ２ , -P(=O)(R Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｃ ) ２ , -OR Ｃ , -SR Ｃ , -S(=O)R Ｄ , -S(=O) ２ R Ｄ , -C(=O)R Ｄ , -C(=O)OR Ｃ , —OC(═O)R Ｄ , -C(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)R Ｄ , -OC(=O)OR Ｃ , -NR Ｃ C(=O)OR Ｄ , -OC(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)N(R Ｃ ) ２ , -S(=O)OR Ｃ , -OS(=O)R Ｄ , -S(=O)N(R Ｃ ) ２ , -NR Ｃ S(=O)R Ｄ , -S(=O) ２ OR Ｃ , -OS(=O) ２ R Ｄ , -S(=O) ２ N (R Ｃ ) ２ , -NR Ｃ S (= O) ２ R Ｄ , -OS(=O) ２ OR Ｃ , -NR Ｃ S (= O) ２ OR Ｃ , -OS(=O) ２ NR Ｃ , -NR Ｃ S (= O) ２ N (R Ｃ ) ２ , -P(R Ｃ ) ２ , -P(=O)(R Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; R ３ teeth, 【Chemistry 10】 and Each R ３１ , R ３２ , R ３３ , R ３４ , R ３５ , R ３６ , R ３８ , R ３９ , R ３１０ , and R ３１１ are independently hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —N(R Ａ ) ２ , -OR Ａ , -SR Ａ , -S(=O)R Ｂ , -S(=O) ２ R Ｂ , -C(=O)R Ｂ , -C(=O)OR Ａ , -C(=O)N(R Ａ ) ２ , -S(=O)OR Ａ , -S(=O)N(R Ａ ) ２ , -S(=O) ２ OR Ａ , -S(=O) ２ N (R Ａ ) ２ , -P(=O)(R Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｃ ) ２ , -OR Ｃ , -SR Ｃ , -S(=O)R Ｄ , -S(=O) ２ R Ｄ , -C(=O)R Ｄ , -C(=O)OR Ｃ , —OC(═O)R Ｄ , -C(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)R Ｄ , -OC(=O)OR Ｃ , -NR Ｃ C(=O)OR Ｄ , -OC(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)N(R Ｃ ) ２ , -S(=O)OR Ｃ , -OS(=O)R Ｄ , -S(=O)N(R Ｃ ) ２ , -NR Ｃ S(=O)R Ｄ , -S(=O) ２ OR Ｃ , -OS(=O) ２ R Ｄ , -S(=O) ２ N (R Ｃ ) ２ , -NR Ｃ S (= O) ２ R Ｄ , -OS(=O) ２ OR Ｃ , -NR Ｃ S (= O) ２ OR Ｃ , -OS(=O) ２ NR Ｃ , -NR Ｃ S (= O) ２ N (R Ｃ ) ２ , -P(R Ｃ ) ２ , -P(=O)(R Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, R ３１ and R ３２ together with the carbon atoms bonded to both of these, 【Chemistry 11】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 12】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３３ is replaced by Optionally, R ３３ and R ３４ together with the carbon atoms bonded to both of these, 【Chemistry 13】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 14】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３４ is replaced by Optionally, R ３５ and R ３６ together with the carbon atoms bonded to both of these, 【Chemistry 15】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 16】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３５ is replaced by Optionally, R ３８ and R ３９ together with the carbon atoms bonded to both of these, 【Chemistry 17】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, [Chemistry 18] The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３１０ is replaced by Optionally, R ３１０ and R ３１１ together with the carbon atoms bonded to both of these, 【Chemistry 19】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 20】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３１６ is replaced by n ２ is 0, 1, 2, 3, 4, 5, or 6, n ３ is 0, 1, 2, 3, 4, 5, or 6, n ４ is 0, 1, 2, 3, 4, 5, or 6, n ５ is 0, 1, 2, 3, 4, 5, or 6, n ６ is 0, 1, 2, 3, 4, 5, or 6, Ring B is a 3- to 10-membered heterocycle, optionally containing N, O, S, S(=O), and S(=O) ２ further comprising 1, 2, or 3 heteroatoms selected from Ring C is a 3- to 10-membered heterocycle, optionally containing N, O, S, S(=O), and S(=O) ２ further comprising 1, 2, or 3 heteroatoms selected from Ring D is a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring; Ring I is a 3- to 10-membered carbocyclic ring or N, O, S, S(=O), and S(=O) ２ is a 3- to 10-membered heterocycle containing 1, 2, or 3 heteroatoms selected from Ring J is a 3- to 10-membered carbocyclic ring, or N, O, S, S(=O), and S(=O) ２ is a 3- to 10-membered heterocycle containing 1, 2, or 3 heteroatoms selected from Ring K is a 3- to 10-membered carbocyclic ring, or N, O, S, S(=O), and S(=O) ２ is a 3- to 10-membered heterocycle containing 1, 2, or 3 heteroatoms selected from R Ｓ３１ is hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３１Ａ ) ２ , -OR Ｓ３１Ａ , -SR Ｓ３１Ａ , -S(=O)R Ｓ３１Ｂ , -S(=O) ２ R Ｓ３１Ｂ , -C(=O)R Ｓ３１Ｂ , -C(=O)OR Ｓ３１Ａ , —OC(═O)R Ｓ３１Ｂ , -C(=O)N(R Ｓ３１Ａ ) ２ , -NR Ｓ３１Ａ C(=O)R Ｓ３１Ｂ , -OC(=O)OR Ｓ３１Ａ , -NR Ｓ３１Ａ C(=O)OR Ｓ３１Ａ , -NR Ｓ３１Ａ C(=S) OR Ｓ３１Ａ , -OC(=O)N(R Ｓ３１Ａ ) ２ , -NR Ｓ３１Ａ C(=O)N(R Ｓ３１Ａ ) ２ , -S(=O)OR Ｓ３１Ａ , -OS(=O)R Ｓ３１Ｂ , -S(=O)N(R Ｓ３１Ａ ) ２ , -NR Ｓ３１Ａ S(=O)R Ｓ３１Ｂ , -S(=O) ２ OR Ｓ３１Ａ , -OS(=O) ２ R Ｓ３１Ｂ , -S(=O) ２ N (R Ｓ３１Ａ ) ２ , -NR Ｓ３１Ａ S (= O) ２ R Ｓ３１Ｂ , -OS(=O) ２ OR Ｓ３１Ａ , -NR Ｓ３１Ａ S (= O) ２ OR Ｓ３１Ａ , -OS(=O) ２ N (R Ｓ３１Ａ ) ２ , -NR Ｓ３１Ａ S (= O) ２ N (R Ｓ３１Ａ ) ２ , -P(R Ｓ３１Ａ ) ２ , -P(=O)(R Ｓ３１Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３１Ｃ ) ２ , -OR Ｓ３１Ｃ , -SR Ｓ３１Ｃ , -S(=O)R Ｓ３１Ｄ , -S(=O) ２ R Ｓ３１Ｄ , -C(=O)R Ｓ３１Ｄ , -C(=O)OR Ｓ３１Ｃ , —OC(═O)R Ｓ３１Ｄ , -C(=O)N(R Ｓ３１Ｃ ) ２ , -NR Ｓ３１Ｃ C(=O)R Ｓ３１Ｄ , -OC(=O)OR Ｓ３１Ｃ , -NR Ｓ３１Ｃ C(=O)OR Ｓ３１Ｃ , -NR Ｓ３１Ｃ C(=S) OR Ｓ３１Ｃ , -OC(=O)N(R Ｓ３１Ｃ ) ２ , -NR Ｓ３１Ｃ C(=O)N(R Ｓ３１Ｃ ) ２ , -S(=O)OR Ｓ３１Ｃ , -OS(=O)R Ｓ３１Ｄ , -S(=O)N(R Ｓ３１Ｃ ) ２ , -NR Ｓ３１Ｃ S(=O)R Ｓ３１Ｄ , -S(=O) ２ OR Ｓ３１Ｃ , -OS(=O) ２ R Ｓ３１Ｄ , -S(=O) ２ N (R Ｓ３１Ｃ ) ２ , -NR Ｓ３１Ｃ S (= O) ２ R Ｓ３１Ｄ , -OS(=O) ２ OR Ｓ３１Ｃ , -NR Ｓ３１Ｃ S (= O) ２ OR Ｓ３１Ｃ , -OS(=O) ２ N (R Ｓ３１Ｃ ) ２ , -NR Ｓ３１Ｃ S (= O) ２ N (R Ｓ３１Ｃ ) ２ , -P(R Ｓ３１Ｃ ) ２ , -P(=O)(R Ｓ３１Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R Ｓ３１ together with the carbon atoms bonded to both of these, 【Chemistry 21】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 22】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３１１ is replaced by Optionally, two adjacent R Ｓ３１ along with the atoms to which they are bonded, 【Chemistry 23】 and forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R Ｓ３１２ is replaced by Optionally, two non-adjacent R Ｓ３１ are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or selected from the group consisting of N, O, S, S=O, and S(=O). ２ and the hydrogen on each carbon or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R Ｓ３１３ is replaced by m ３ is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, R Ｓ３２ is hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３２Ａ ) ２ , -OR Ｓ３２Ａ , -SR Ｓ３２Ａ , -S(=O)R Ｓ３２Ｂ , -S(=O) ２ R Ｓ３２Ｂ , -C(=O)R Ｓ３２Ｂ , -C(=O)OR Ｓ３２Ａ , —OC(═O)R Ｓ３２Ｂ , -C(=O)N(R Ｓ３２Ａ ) ２ , -NR Ｓ３２Ａ C(=O)R Ｓ３２Ｂ , -OC(=O)OR Ｓ３２Ａ , -NR Ｓ３２Ａ C(=O)OR Ｓ３２Ａ , -NR Ｓ３２Ａ C(=S) OR Ｓ３２Ａ , -OC(=O)N(R Ｓ３２Ａ ) ２ , -NR Ｓ３２Ａ C(=O)N(R Ｓ３２Ａ ) ２ , -S(=O)OR Ｓ３２Ａ , -OS(=O)R Ｓ３２Ｂ , -S(=O)N(R Ｓ３２Ａ ) ２ , -NR Ｓ３２Ａ S(=O)R Ｓ３２Ｂ , -S(=O) ２ OR Ｓ３２Ａ , -OS(=O) ２ R Ｓ３２Ｂ , -S(=O) ２ N (R Ｓ３２Ａ ) ２ , -NR Ｓ３２Ａ S (= O) ２ R Ｓ３２Ｂ , -OS(=O) ２ OR Ｓ３２Ａ , -NR Ｓ３２Ａ S (= O) ２ OR Ｓ３２Ａ , -OS(=O) ２ N (R Ｓ３２Ａ ) ２ , -NR Ｓ３２Ａ S (= O) ２ N (R Ｓ３２Ａ ) ２ , -P(R Ｓ３２Ａ ) ２ , -P(=O)(R Ｓ３２Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３２Ｃ ) ２ , -OR Ｓ３２Ｃ , -SR Ｓ３２Ｃ , -S(=O)R Ｓ３２Ｃ , -S(=O) ２ R Ｓ３２Ｄ , -C(=O)R Ｓ３２Ｄ , -C(=O)OR Ｓ３２Ｃ , —OC(═O)R Ｓ３２Ｄ , -C(=O)N(R Ｓ３２Ｃ ) ２ , -NR Ｓ３２Ｃ C(=O)R Ｓ３２Ｄ , -OC(=O)OR Ｓ３２Ｃ , -NR Ｓ３２Ｃ C(=O)OR Ｓ３２Ｃ , -NR Ｓ３２Ｃ C(=S) OR Ｓ３２Ｃ , -OC(=O)N(R Ｓ３２Ｃ ) ２ , -NR Ｓ３２Ｃ C(=O)N(R Ｓ３２Ｃ ) ２ , -S(=O)OR Ｓ３２Ｃ , -OS(=O)R Ｓ３２Ｃ , -S(=O)N(R Ｓ３２Ｃ ) ２ , -NR Ｓ３２Ｃ S(=O)R Ｓ３２Ｄ , -S(=O) ２ OR Ｓ３２Ｃ , -OS(=O) ２ R Ｓ３２Ｄ , -S(=O) ２ N (R Ｓ３２Ｃ ) ２ , -NR Ｓ３２Ｃ S (= O) ２ R Ｓ３２Ｄ , -OS(=O) ２ OR Ｓ３２Ｃ , -NR Ｓ３２Ｃ S (= O) ２ OR Ｓ３２Ｃ , -OS(=O) ２ N (R Ｓ３２Ｃ ) ２ , -NR Ｓ３２Ｃ S (= O) ２ N (R Ｓ３２Ｃ ) ２ , -P(R Ｓ３２Ｃ ) ２ , -P(=O)(R Ｓ３２Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R Ｓ３２ together with the carbon atoms bonded to both of these, 【Chemistry 24】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 25】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３２１ is replaced by Optionally, two adjacent R Ｓ３２ along with the atoms to which they are bonded, 【Chemistry 26】 and forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R Ｓ３２２ is replaced by Optionally, two non-adjacent R Ｓ３２ are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or selected from the group consisting of N, O, S, S=O, and S(=O). ２ and the hydrogen on each carbon or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R Ｓ３２３ is replaced by m ４ is 0, 1, 2, 3, 4, 5, or 6, R ３７ is -N(R ３７Ａ ) ２ or a 3- to 10-membered heterocyclyl group, wherein said 3- to 10-membered heterocyclyl group optionally independently comprises one or more R ３７ is replaced by R Ｓ３８ is hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３８Ａ ) ２ , -OR Ｓ３８Ａ , -SR Ｓ３８Ａ , -S(=O)R Ｓ３８Ｂ , -S(=O) ２ R Ｓ３８Ｂ , -C(=O)R Ｓ３８Ｂ , -C(=O)OR Ｓ３８Ａ , —OC(═O)R Ｓ３８Ｂ , -C(=O)N(R Ｓ３８Ａ ) ２ , -NR Ｓ３８Ａ C(=O)R Ｓ３８Ｂ , -OC(=O)OR Ｓ３８Ａ , -NR Ｓ３８Ａ C(=O)OR Ｓ３８Ａ , -NR Ｓ３８Ａ C(=S) OR Ｓ３８Ａ , -OC(=O)N(R Ｓ３８Ａ ) ２ , -NR Ｓ３８Ａ C(=O)N(R Ｓ３８Ａ ) ２ , -S(=O)OR Ｓ３８Ａ , -OS(=O)R Ｓ３８Ｂ , -S(=O)N(R Ｓ３８Ａ ) ２ , -NR Ｓ３８Ａ S(=O)R Ｓ３８Ｂ , -S(=O) ２ OR Ｓ３８Ａ , -OS(=O) ２ R Ｓ３８Ｂ , -S(=O) ２ N (R Ｓ３８Ａ ) ２ , -NR Ｓ３８Ａ S (= O) ２ R Ｓ３８Ｂ , -OS(=O) ２ OR Ｓ３８Ａ , -NR Ｓ３８Ａ S (= O) ２ OR Ｓ３８Ａ , -OS(=O) ２ N (R Ｓ３８Ａ ) ２ , -NR Ｓ３８Ａ S (= O) ２ N (R Ｓ３８Ａ ) ２ , -P(R Ｓ３８Ａ ) ２ , -P(=O)(R Ｓ３８Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３８Ｃ ) ２ , -OR Ｓ３８Ｃ , -SR Ｓ３８Ｃ , -S(=O)R Ｓ３８Ｄ , -S(=O) ２ R Ｓ３８Ｄ , -C(=O)R Ｓ３８Ｄ , -C(=O)OR Ｓ３８Ｃ , —OC(═O)R Ｓ３８Ｄ , -C(=O)N(R Ｓ３８Ｃ ) ２ , -NR Ｓ３８Ｃ C(=O)R Ｓ３８Ｄ , -OC(=O)OR Ｓ３８Ｃ , -NR Ｓ３８Ｃ C(=O)OR Ｓ３８Ｃ , -NR Ｓ３８Ｃ C(=S) OR Ｓ３８Ｃ , -OC(=O)N(R Ｓ３８Ｃ ) ２ , -NR Ｓ３８Ｃ C(=O)N(R Ｓ３８Ｃ ) ２ , -S(=O)OR Ｓ３８Ｃ , -OS(=O)R Ｓ３８Ｄ , -S(=O)N(R Ｓ３８Ｃ ) ２ , -NR Ｓ３８Ｃ S(=O)R Ｓ３８Ｄ , -S(=O) ２ OR Ｓ３８Ｃ , -OS(=O) ２ R Ｓ３８Ｄ , -S(=O) ２ N (R Ｓ３８Ｃ ) ２ , -NR Ｓ３８Ｃ S (= O) ２ R Ｓ３８Ｄ , -OS(=O) ２ OR Ｓ３８Ｃ , -NR Ｓ３８Ｃ S (= O) ２ OR Ｓ３８Ｃ , -OS(=O) ２ N (R Ｓ３８Ｃ ) ２ , -NR Ｓ３８Ｃ S (= O) ２ N (R Ｓ３８Ｃ ) ２ , -P(R Ｓ３８Ｃ ) ２ , -P(=O)(R Ｓ３８Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R Ｓ３８ together with the carbon atoms bonded to both of these, 【Chemistry 27】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 28】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３８１ is replaced by Optionally, two adjacent R Ｓ３８ along with the atoms to which they are bonded, 【Chemistry 29】 and forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R Ｓ３８２ is replaced by Optionally, two non-adjacent R Ｓ３８ are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or selected from the group consisting of N, O, S, S=O, and S(=O). ２ and the hydrogen on each carbon or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R Ｓ３８３ is replaced by m ８ is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, R Ｓ３９ is hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３９Ａ ) ２ , -OR Ｓ３９Ａ , -SR Ｓ３９Ａ , -S(=O)R Ｓ３９Ｂ , -S(=O) ２ R Ｓ３９Ｂ , -C(=O)R Ｓ３９Ｂ , -C(=O)OR Ｓ３９Ａ , —OC(═O)R Ｓ３９Ｂ , -C(=O)N(R Ｓ３９Ａ ) ２ , -NR Ｓ３９Ａ C(=O)R Ｓ３９Ｂ , -OC(=O)OR Ｓ３９Ａ , -NR Ｓ３９Ａ C(=O)OR Ｓ３９Ａ , -NR Ｓ３９Ａ C(=S) OR Ｓ３９Ａ , -OC(=O)N(R Ｓ３９Ａ ) ２ , -NR Ｓ３９Ａ C(=O)N(R Ｓ３９Ａ ) ２ , -S(=O)OR Ｓ３９Ａ , -OS(=O)R Ｓ３９Ｂ , -S(=O)N(R Ｓ３９Ａ ) ２ , -NR Ｓ３９Ａ S(=O)R Ｓ３９Ｂ , -S(=O) ２ OR Ｓ３９Ａ , -OS(=O) ２ R Ｓ３９Ｂ , -S(=O) ２ N (R Ｓ３９Ａ ) ２ , -NR Ｓ３９Ａ S (= O) ２ R Ｓ３９Ｂ , -OS(=O) ２ OR Ｓ３９Ａ , -NR Ｓ３９Ａ S (= O) ２ OR Ｓ３９Ａ , -OS(=O) ２ N (R Ｓ３９Ａ ) ２ , -NR Ｓ３９Ａ S (= O) ２ N (R Ｓ３９Ａ ) ２ , -P(R Ｓ３９Ａ ) ２ , -P(=O)(R Ｓ３９Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３９Ｃ ) ２ , -OR Ｓ３９Ｃ , -SR Ｓ３９Ｃ , -S(=O)R Ｓ３９Ｃ , -S(=O) ２ R Ｓ３９Ｄ , -C(=O)R Ｓ３９Ｄ , -C(=O)OR Ｓ３９Ｃ , —OC(═O)R Ｓ３９Ｄ , -C(=O)N(R Ｓ３９Ｃ ) ２ , -NR Ｓ３９Ｃ C(=O)R Ｓ３９Ｄ , -OC(=O)OR Ｓ３９Ｃ , -NR Ｓ３９Ｃ C(=O)OR Ｓ３９Ｃ , -NR Ｓ３９Ｃ C(=S) OR Ｓ３９Ｃ , -OC(=O)N(R Ｓ３９Ｃ ) ２ , -NR Ｓ３９Ｃ C(=O)N(R Ｓ３９Ｃ ) ２ , -S(=O)OR Ｓ３９Ｃ , -OS(=O)R Ｓ３９Ｃ , -S(=O)N(R Ｓ３９Ｃ ) ２ , -NR Ｓ３９Ｃ S(=O)R Ｓ３９Ｄ , -S(=O) ２ OR Ｓ３９Ｃ , -OS(=O) ２ R Ｓ３９Ｄ , -S(=O) ２ N (R Ｓ３９Ｃ ) ２ , -NR Ｓ３９Ｃ S (= O) ２ R Ｓ３９Ｄ , -OS(=O) ２ OR Ｓ３９Ｃ , -NR Ｓ３９Ｃ S (= O) ２ OR Ｓ３９Ｃ , -OS(=O) ２ N (R Ｓ３９Ｃ ) ２ , -NR Ｓ３９Ｃ S (= O) ２ N (R Ｓ３９Ｃ ) ２ , -P(R Ｓ３９Ｃ ) ２ , -P(=O)(R Ｓ３９Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R Ｓ３９ together with the carbon atoms bonded to both of these, 【Transformation 30】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Chemistry 31】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３９１ is replaced by Optionally, two adjacent R Ｓ３９ along with the atoms to which they are bonded, 【Chemistry 32】 and forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R Ｓ３９２ is replaced by Optionally, two non-adjacent R Ｓ３９ are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or selected from the group consisting of N, O, S, S=O, and S(=O). ２ and the hydrogen on each carbon or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R Ｓ３９３ is replaced by m ９ is 0, 1, 2, 3, 4, 5, or 6, R Ｓ３１５ is hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３１５Ａ ) ２ , -OR Ｓ３１５Ａ , -SR Ｓ３１５Ａ , -S(=O)R Ｓ３１５Ｂ , -S(=O) ２ R Ｓ３１５Ｂ , -C(=O)R Ｓ３１５Ｂ , -C(=O)OR Ｓ３１５Ａ , —OC(═O)R Ｓ３１５Ｂ , -C(=O)N(R Ｓ３１５Ａ ) ２ , -NR Ｓ３１５Ａ C(=O)R Ｓ３１５Ｂ , -OC(=O)OR Ｓ３１５Ａ , -NR Ｓ３１５Ａ C(=O)OR Ｓ３１５Ａ , -NR Ｓ３１５Ａ C(=S) OR Ｓ３１５Ａ , -OC(=O)N(R Ｓ３１５Ａ ) ２ , -NR Ｓ３１５Ａ C(=O)N(R Ｓ３１５Ａ ) ２ , -S(=O)OR Ｓ３１５Ａ , -OS(=O)R Ｓ３１５Ｂ , -S(=O)N(R Ｓ３１５Ａ ) ２ , -NR Ｓ３１５Ａ S(=O)R Ｓ３１５Ｂ , -S(=O) ２ OR Ｓ３１５Ａ , -OS(=O) ２ R Ｓ３１５Ｂ , -S(=O) ２ N (R Ｓ３１５Ａ ) ２ , -NR Ｓ３１５Ａ S (= O) ２ R Ｓ３１５Ｂ , -OS(=O) ２ OR Ｓ３１５Ａ , -NR Ｓ３１５Ａ S (= O) ２ OR Ｓ３１５Ａ , -OS(=O) ２ N (R Ｓ３１５Ａ ) ２ , -NR Ｓ３１５Ａ S (= O) ２ N (R Ｓ３１５Ａ ) ２ , -P(R Ｓ３１５Ａ ) ２ , -P(=O)(R Ｓ３１５Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ３１５Ｃ ) ２ , -OR Ｓ３１５Ｃ , -SR Ｓ３１５Ｃ , -S(=O)R Ｓ３１５Ｃ , -S(=O) ２ R Ｓ３１５Ｄ , -C(=O)R Ｓ３１５Ｄ , -C(=O)OR Ｓ３１５Ｃ , —OC(═O)R Ｓ３１５Ｄ , -C(=O)N(R Ｓ３１５Ｃ ) ２ , -NR Ｓ３１５Ｃ C(=O)R Ｓ３１５Ｄ , -OC(=O)OR Ｓ３１５Ｃ , -NR Ｓ３１５Ｃ C(=O)OR Ｓ３１５Ｃ , -NR Ｓ３１５Ｃ C(=S) OR Ｓ３１５Ｃ , -OC(=O)N(R Ｓ３１５Ｃ ) ２ , -NR Ｓ３１５Ｃ C(=O)N(R Ｓ３１５Ｃ ) ２ , -S(=O)OR Ｓ３１５Ｃ , -OS(=O)R Ｓ３１５Ｃ , -S(=O)N(R Ｓ３１５Ｃ ) ２ , -NR Ｓ３１５Ｃ S(=O)R Ｓ３１５Ｄ , -S(=O) ２ OR Ｓ３１５Ｃ , -OS(=O) ２ R Ｓ３１５Ｄ , -S(=O) ２ N (R Ｓ３１５Ｃ ) ２ , -NR Ｓ３１５Ｃ S (= O) ２ R Ｓ３１５Ｄ , -OS(=O) ２ OR Ｓ３１５Ｃ , -NR Ｓ３１５Ｃ S (= O) ２ OR Ｓ３１５Ｃ , -OS(=O) ２ N (R Ｓ３１５Ｃ ) ２ , -NR Ｓ３１５Ｃ S (= O) ２ N (R Ｓ３１５Ｃ ) ２ , -P(R Ｓ３１５Ｃ ) ２ , -P(=O)(R Ｓ３１５Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R Ｓ３１５ together with the carbon atoms bonded to both of these, 【Transformation 33】 Forms a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring, 【Transformation 34】 The 3- to 10-membered carbocyclic or 3- to 10-membered heterocyclic ring is independently unsubstituted or substituted with one or more R Ｓ３１５１ is replaced by Optionally, two adjacent R Ｓ３１５ along with the atoms to which they are bonded, 【Chemistry 35】 and forming a 3- to 10-membered carbocyclic ring, a 3- to 10-membered heterocyclic ring, a 6- to 10-membered aromatic ring, or a 5- to 10-membered heteroaromatic ring, wherein each ring is independently unsubstituted or contains one or more R Ｓ３１５２ is replaced by Optionally, two non-adjacent R Ｓ３１５ are bonded together to form a bridged structure containing 0, 1, 2, 3, 4, 5, or 6 carbon atoms, wherein each carbon atom in the bridged structure is independently unsubstituted or selected from the group consisting of N, O, S, S=O, and S(=O). ２ and the hydrogen on each carbon or N atom is independently unsubstituted or replaced by one or two heteroatoms selected from R Ｓ３１５３ is replaced by m １０ is 0, 1, 2, 3, 4, 5, or 6, R ４ represents a 6- to 10-membered aryl group, a 5- to 10-membered heteroaryl group, 【Transformation 36】 wherein the 6- to 10-membered aryl group, the 5- to 10-membered heteroaryl group, 【Chemistry 37】 is independently unsubstituted or is substituted with one or more R Ｓ４ is replaced by Z, in each occurrence, is independently C or N; when Z is C, ring E in each occurrence is independently a 6-membered aromatic ring or a 5- to 6-membered heteroaromatic ring, and ring F in each occurrence is independently a 3- to 10-membered carbocycle or a 3- to 10-membered heterocycle; when Z is N, ring E in each occurrence is independently a 5- to 6-membered heteroaromatic ring, and ring F in each occurrence is independently a 3- to 10-membered heterocyclic ring; R Ｓ４ are independently deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ４Ａ ) ２ , -OR Ｓ４Ａ , -SR Ｓ４Ａ , -S(=O)R Ｓ４Ｂ , -S(=O) ２ R Ｓ４Ｂ , -C(=O)R Ｓ４Ｂ , -C(=O)OR Ｓ４Ａ , —OC(═O)R Ｓ４Ｂ , -C(=O)N(R Ｓ４Ａ ) ２ , -NR Ｓ４Ａ C(=O)R Ｓ４Ｂ , -OC(=O)OR Ｓ４Ａ , -NR Ｓ４Ａ C(=O)OR Ｓ４Ａ , -NR Ｓ４Ａ C(=S) OR Ｓ４Ａ , -OC(=O)N(R Ｓ４Ａ ) ２ , -NR Ｓ４Ａ C(=O)N(R Ｓ４Ａ ) ２ , -S(=O)OR Ｓ４Ａ , -OS(=O)R Ｓ４Ｂ , -S(=O)N(R Ｓ４Ａ ) ２ , -NR Ｓ４Ａ S(=O)R Ｓ４Ｂ , -S(=O) ２ OR Ｓ４Ａ , -OS(=O) ２ R Ｓ４Ｂ , -S(=O) ２ N (R Ｓ４Ａ ) ２ , -NR Ｓ４Ａ S (= O) ２ R Ｓ４Ｂ , -OS(=O) ２ OR Ｓ４Ａ , -NR Ｓ４Ａ S (= O) ２ OR Ｓ４Ａ , -OS(=O) ２ N (R Ｓ４Ａ ) ２ , -NR Ｓ４Ａ S (= O) ２ N (R Ｓ４Ａ ) ２ , -P(R Ｓ４Ａ ) ２ , -P(=O)(R Ｓ４Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｓ４Ｃ ) ２ , -OR Ｓ４Ｃ , -SR Ｓ４Ｃ , -S(=O)R Ｓ４Ｄ , -S(=O) ２ R Ｓ４Ｄ , -C(=O)R Ｓ４Ｄ , -C(=O)OR Ｓ４Ｄ , —OC(═O)R Ｓ４Ｄ , -C(=O)N(R Ｓ４Ｃ ) ２ , -NR Ｓ４Ｃ C(=O)R Ｓ４Ｄ , -OC(=O)OR Ｓ４Ｃ , -NR Ｓ４Ｃ C(=O)OR Ｓ４Ｃ , -NR Ｓ４Ｃ C(=S) OR Ｓ４Ｃ , -OC(=O)N(R Ｓ４Ｃ ) ２ , -NR Ｓ４Ｃ C(=O)N(R Ｓ４Ｃ ) ２ , -S(=O)OR Ｓ４Ｃ , -OS(=O)R Ｓ４Ｄ , -S(=O)N(R Ｓ４Ｃ ) ２ , -NR Ｓ４Ｃ S(=O)R Ｓ４Ｄ , -S(=O) ２ OR Ｓ４Ｃ , -OS(=O) ２ R Ｓ４Ｄ , -S(=O) ２ N (R Ｓ４Ｃ ) ２ , -NR Ｓ４Ｃ S (= O) ２ R Ｓ４Ｄ , -OS(=O) ２ OR Ｓ４Ｃ , -NR Ｓ４Ｃ S (= O) ２ OR Ｓ４Ｃ , -OS(=O) ２ N (R Ｓ４Ｃ ) ２ , -NR Ｓ４Ｃ S (= O) ２ N (R Ｓ４Ｃ ) ２ , -P(R Ｓ４Ｃ ) ２ , -P(=O)(R Ｓ４Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; R ５ is hydrogen, deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R ５Ａ ) ２ , -OR ５Ａ , -SR ５Ａ , -S(=O)R ５Ｂ , -S(=O) ２ R ５Ｂ , -C(=O)R ５Ｂ , -C(=O)OR ５Ａ , —OC(═O)R ５Ｂ , -C(=O)N(R ５Ａ ) ２ , -NR ５Ａ C(=O)R ５Ｂ , -OC(=O)OR ５Ａ , -NR ５Ａ C(=O)OR ５Ａ , -NR ５Ａ C(=S) OR ５Ａ , -OC(=O)N(R ５Ａ ) ２ , -NR ５Ａ C(=O)N(R ５Ａ ) ２ , -S(=O)OR ５Ａ , -OS(=O)R ５Ｂ , -S(=O)N(R ５Ａ ) ２ , -NR ５Ａ S(=O)R ５Ｂ , -S(=O) ２ OR ５Ａ , -OS(=O) ２ R ５Ｂ , -S(=O) ２ N (R ５Ａ ) ２ , -NR ５Ａ S (= O) ２ R ５Ｂ , -OS(=O) ２ OR ５Ａ , -NR ５Ａ S (= O) ２ OR ５Ａ , -OS(=O) ２ N (R ５Ａ ) ２ , -NR ５Ａ S (= O) ２ N (R ５Ａ ) ２ , -P(R ５Ａ ) ２ , -P(=O)(R ５Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R ５Ｃ ) ２ , -OR ５Ｃ , -SR ５Ｃ , -S(=O)R ５Ｄ , -S(=O) ２ R ５Ｄ , -C(=O)R ５Ｄ , -C(=O)OR ５Ｄ , —OC(═O)R ５Ｄ , -C(=O)N(R ５Ｃ ) ２ , -NR ５Ｃ C(=O)R ５Ｄ , -OC(=O)OR ５Ｃ , -NR ５Ｃ C(=O)OR ５Ｃ , -NR ５Ｃ C(=S) OR ５Ｃ , -OC(=O)N(R ５Ｃ ) ２ , -NR ５Ｃ C(=O)N(R ５Ｃ ) ２ , -S(=O)OR ５Ｃ , -OS(=O)R ５Ｄ , -S(=O)N(R ５Ｃ ) ２ , -NR ５Ｃ S(=O)R ５Ｄ , -S(=O) ２ OR ５Ｃ , -OS(=O) ２ R ５Ｄ , -S(=O) ２ N (R ５Ｃ ) ２ , -NR ５Ｃ S (= O) ２ R ５Ｄ , -OS(=O) ２ OR ５Ｃ , -NR ５Ｃ S (= O) ２ OR ５Ｃ , -OS(=O) ２ N (R ５Ｃ ) ２ , -NR ５Ｃ S (= O) ２ N (R ５Ｃ ) ２ , -P(R ５Ｃ ) ２ , -P(=O)(R ５Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Each R １Ａ , R １Ｃ , R Ｓ１Ａ , R Ｓ１Ｃ , R Ｓ２Ａ , R Ｓ２Ｃ , R Ｓ３１Ａ , R Ｓ３１Ｃ , R Ｓ３２Ａ , R Ｓ３２Ｃ , R ３７Ａ , R Ｓ３８Ａ , R Ｓ３８Ｃ , R Ｓ３９Ａ , R Ｓ３９Ｃ , R Ｓ３１５Ａ , R Ｓ３１５Ｃ , R Ｓ４Ａ , R Ｓ４Ｃ , R ５Ａ , R ５Ｃ , R ａ , R ｂ , R ｃ , R ｄ , R ｅ , R ｆ , R ｇ , R ｈ , R ｉ , R ｊ , R ｋ , and R ｌ are independently hydrogen, deuterium, -C １－６ Alkyl group, halogenated C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —S(═O)R Ｂ , -S(=O) ２ R Ｂ , -C(=O)R Ｂ , -C(=O)OR Ｂ , -C(=O)N(R Ｂ ) ２ , -S(=O)OR Ｂ , -S(=O)N(R Ｂ ) ２ , -S(=O) ２ OR Ｂ , -S(=O) ２ N (R Ｂ ) ２ , -P(=O)(R Ｂ ) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -N(R Ｃ ) ２ , -OR Ｃ , -SR Ｃ , -S(=O)R Ｄ , -S(=O) ２ R Ｄ , -C(=O)R Ｄ , -C(=O)OR Ｃ , —OC(═O)R Ｄ , -C(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)R Ｄ , -OC(=O)OR Ｃ , -NR Ｃ C(=O)OR Ｄ , -OC(=O)N(R Ｃ ) ２ , -NR Ｃ C(=O)N(R Ｃ ) ２ , -S(=O)OR Ｃ , -OS(=O)R Ｄ , -S(=O)N(R Ｃ ) ２ , -NR Ｃ S(=O)R Ｄ , -S(=O) ２ OR Ｃ , -OS(=O) ２ R Ｄ , -S(=O) ２ N (R Ｃ ) ２ , -NR Ｃ S (= O) ２ R Ｄ , -OS(=O) ２ OR Ｃ , -NR Ｃ S (= O) ２ OR Ｃ , -OS(=O) ２ NR Ｃ , -NR Ｃ S (= O) ２ N (R Ｃ ) ２ , -P(R Ｃ ) ２ , -P(=O)(R Ｄ ) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Optionally, two R １Ａ , two R １Ｃ , two R Ｓ１Ａ , two R Ｓ１Ｃ , two R Ｓ２Ａ , two R Ｓ２Ｃ , two R Ｓ３１Ａ , two R Ｓ３１Ｃ , two R Ｓ３２Ａ , two R Ｓ３２Ｃ , two R ３７Ａ , two R Ｓ３８Ａ , two R Ｓ３８Ｃ , two R Ｓ３９Ａ , two R Ｓ３９Ｃ , two R Ｓ３１５Ａ , two R Ｓ３１５Ｃ , two R Ｓ４Ａ , two R Ｓ４Ｃ , two R ５Ａ , or two R ５Ｃ together with the nitrogen atom to which they are both bonded, form a 3- to 10-membered heterocyclic ring or a 5- to 10-membered heteroaromatic ring, wherein said 3- to 10-membered heterocyclic ring or said 5- to 10-membered heteroaromatic ring is independently unsubstituted or substituted with one or more R ＳＳ is replaced by Each R １Ｂ , R １Ｄ , R Ｓ１Ｂ , R Ｓ１Ｄ , R Ｓ２Ｂ , R Ｓ２Ｄ , R Ｓ３１Ｂ , R Ｓ３１Ｄ , R Ｓ３２Ｂ , R Ｓ３２Ｄ , R Ｓ３８Ｂ , R Ｓ３８Ｄ , R Ｓ３９Ｂ , R Ｓ３１５Ｂ , R Ｓ３１５Ｄ , R Ｓ３９Ｄ , R Ｓ４Ｂ , R Ｓ４Ｄ , R ５Ｂ , and R ５Ｄ are independently hydrogen, deuterium, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, halogenated C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C ２－６ Alkynyl group, —N(R Ａ ) ２ , -OR Ａ , -SR Ａ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ alkynyl group, -CN, -NO ２ , -N ３ , oxo, -N(R Ｃ ), ２ , -OR Ｃ , -SR Ｃ , -S(=O)R Ｄ , -S(=O) ２ R Ｄ , -C(=O)R Ｄ , -C(=O)OR Ｃ , -OC(=O)R Ｄ , -C(=O)N(R Ｃ ), ２ , -NR Ｃ C(=O)R Ｄ , -OC(=O)OR Ｃ , -NR Ｃ C(=O)OR Ｄ , -OC(=O)N(R Ｃ ), ２ , -NR Ｃ C(=O)N(R Ｃ ), ２ , -S(=O)OR Ｃ , -OS(=O)R Ｄ , -S(=O)N(R Ｃ ), ２ , -NR Ｃ S(=O)R Ｄ , -S(=O) ２ OR Ｃ , -OS(=O) ２ R Ｄ , -S(=O) ２ N(R Ｃ ), ２ , -NR Ｃ S(=O) ２ R Ｄ , -OS(=O) ２ OR Ｃ , -NR Ｃ S(=O) ２ OR Ｃ , -OS(=O) ２ NR Ｃ , -NR Ｃ S(=O) ２ N(R Ｃ ), ２ , -P(R Ｃ ), ２ , -P(=O)(R Ｄ ), ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Each R Ａ , R Ｂ , R Ｃ , and R Ｄ are independently hydrogen, deuterium, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ an alkynyl group, a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with one or more R ＳＡ is replaced by Each R ＳＸ１ , R Ｓ１１ , R Ｓ１２ , R Ｓ１３ , R Ｓ２１ , R Ｓ２２ , R Ｓ２３ , R Ｓ３３ , R Ｓ３４ , R Ｓ３５ , R Ｓ３７ , R Ｓ３１０ , R Ｓ３１６ , R Ｓ３１１ , R Ｓ３１２ , R Ｓ３１３ , R Ｓ３２１ , R Ｓ３２２ , R Ｓ３２３ , R Ｓ３８１ , R Ｓ３８２ , R Ｓ３８３ , R Ｓ３９１ , R Ｓ３９２ , R Ｓ３９３ , R Ｓ３１５１ , R Ｓ３１５２ , R Ｓ３１５３ , R ＳＳ , and R ＳＡ are independently deuterium, halogen, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, —O(C １－６ alkyl group), -SH, -S(C １－６ alkyl group), -S(=O)(C １－６ alkyl group), -S(=O) ２ (C １－６ alkyl group), -C(=O)(C １－６ alkyl group), —C(═O)OH, —C(═O)(OC １－６ alkyl group), —OC(═O)(C １－６ alkyl group), —C(═O)NH ２ , -C(=O)NH(C １－６ alkyl group), -C(=O)N(C １－６ alkyl group) ２ , -NHC(=O)(C １－６ alkyl group), -N(C １－６ alkyl group)C(=O)(C １－６ alkyl group), —OC(═O)O(C １－６ alkyl group), -NHC(=O)(OC １－６ alkyl group), -N(C １－６ alkyl group)C(=O)(OC １－６ alkyl group), —OC(═O)NH(C １－６ alkyl group), —OC(═O)N(C １－６ alkyl group) ２ , -NHC(=O)NH ２ , -NHC(=O)NH(C １－６ alkyl group), -NHC(=O)N(C １－６ alkyl group) ２ , -N(C １－６ alkyl group)C(=O)NH ２ , -N(C １－６ alkyl group)C(=O)NH(C １－６ alkyl group), -N(C １－６ alkyl group)C(=O)N(C １－６ alkyl group) ２ , -S(=O)(OC １－６ alkyl group), —OS(═O)(C １－６ alkyl group), -S(=O)NH ２ , -S(=O)NH(C １－６ alkyl group), -S(=O)N(C １－６ alkyl group) ２ , -NHS(=O)(C １－６ alkyl group), -N(C １－６ alkyl group)S(=O)(C １－６ alkyl group), -S(=O) ２ (OC １－６ alkyl group), —OS(═O) ２ (C １－６ alkyl group), -S(=O) ２ NH ２ , -S(=O) ２ NH (C １－６ alkyl group), -S(=O) ２ N (C １－６ alkyl group) ２ , -NHS(=O) ２ (C １－６ alkyl group), -N(C １－６ alkyl group)S(=O) ２ (C １－６ alkyl group), —OS(═O) ２ O (C １－６ alkyl group), -NHS(=O) ２ O (C １－６ alkyl group), -N(C １－６ alkyl group)S(=O) ２ O (C １－６ alkyl group), —OS(═O) ２ NH ２ , -OS(=O) ２ NH (C １－６ alkyl group), —OS(═O) ２ N (C １－６ alkyl group) ２ , -NHS(=O) ２ NH ２ , -NHS(=O) ２ NH (C １－６ alkyl group), -NHS(=O) ２ N (C １－６ alkyl group) ２ , -N(C １－６ alkyl group)S(=O) ２ NH ２ , -N(C １－６ alkyl group)S(=O) ２ NH (C １－６ alkyl group), -N(C １－６ alkyl group)S(=O) ２ N (C １－６ alkyl group) ２ , -PH(C １－６ alkyl group), -P(C １－６ alkyl group) ２ , -P(=O)H(C １－６ alkyl group), -P(=O)(C １－６ alkyl group) ２ , a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ The alkynyl group, the 3- to 10-membered cycloalkyl group, the 3- to 10-membered cycloalkenyl group, the 3- to 10-membered cycloalkynyl group, the 3- to 10-membered heterocyclyl group, the 6- to 10-membered aryl group, or the 5- to 10-membered heteroaryl group is independently unsubstituted or substituted with deuterium, halogen, —C １－３ Alkyl group, halogenated C １－３ Alkyl group, halogenated C １－３ Alkoxy group, —C ２－３ Alkenyl group, —C ２－３ Alkynyl group, —CN, —NO ２ , -N ３ , oxo, -NH ２ , —NH(C １－３ alkyl group), -N(C １－３ alkyl group) ２ , —OH, —O(C １－３ alkyl group), -SH, -S(C １－３ alkyl group), -S(=O)(C １－３ alkyl group), -S(=O) ２ (C １－３ alkyl group), -C(=O)(C １－３ alkyl group), —C(═O)OH, —C(═O)(OC １－３ alkyl group), —OC(═O)(C １－３ alkyl group), —C(═O)NH ２ , -C(=O)NH(C １－３ alkyl group), -C(=O)N(C １－３ alkyl group) ２ , -NHC(=O)(C １－３ alkyl group), -N(C １－３ alkyl group)C(=O)(C １－３ alkyl group), —OC(═O)O(C １－３ alkyl group), -NHC(=O)(OC １－３ alkyl group), -N(C １－３ alkyl group)C(=O)(OC １－３ alkyl group), —OC(═O)NH(C １－３ alkyl group), —OC(═O)N(C １－３ alkyl group) ２ , -NHC(=O)NH ２ , -NHC(=O)NH(C １－３ alkyl group), -NHC(=O)N(C １－３ alkyl group) ２ , -N(C １－３ alkyl group)C(=O)NH ２ , -N(C １－３ alkyl group)C(=O)NH(C １－３ alkyl group), -N(C １－３ alkyl group)C(=O)N(C １－３ alkyl group) ２ , -S(=O)(OC １－３ alkyl group), —OS(═O)(C １－３ alkyl group), -S(=O)NH ２ , -S(=O)NH(C １－３ alkyl group), -S(=O)N(C １－３ alkyl group) ２ , -NHS(=O)(C １－３ alkyl group), -N(C １－３ alkyl group)S(=O)(C １－３ alkyl group), -S(=O) ２ (OC １－３ alkyl group), —OS(═O) ２ (C １－３ alkyl group), -S(=O) ２ NH ２ , -S(=O) ２ NH (C １－３ alkyl group), -S(=O) ２ N (C １－３ alkyl group) ２ , -NHS(=O) ２ (C １－３ alkyl group), -N(C １－３ alkyl group)S(=O) ２ (C １－３ alkyl group), —OS(═O) ２ O (C １－３ alkyl group), -NHS(=O) ２ O (C １－３ alkyl group), -N(C １－３ alkyl group)S(=O) ２ O (C １－３ alkyl group), —OS(═O) ２ NH ２ , -OS(=O) ２ NH (C １－３ alkyl group), —OS(═O) ２ N (C １－３ alkyl group) ２ , -NHS(=O) ２ NH ２ , -NHS(=O) ２ NH (C １－３ alkyl group), -NHS(=O) ２ N (C １－３ alkyl group) ２ , -N(C １－３ alkyl group)S(=O) ２ NH ２ , -N(C １－３ alkyl group)S(=O) ２ NH (C １－３ alkyl group), -N(C １－３ alkyl group)S(=O) ２ N (C １－３ alkyl group) ２ , -PH(C １－３ alkyl group), -P(C １－３ alkyl group) ２ , -P(=O)H(C １－３ alkyl group), -P(=O)(C １－３ alkyl group) ２ , substituted with one or more substituents selected from a 3- to 10-membered cycloalkyl group, a 3- to 10-membered cycloalkenyl group, a 3- to 10-membered cycloalkynyl group, a 3- to 10-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; Each heterocyclyl group or heterocycle, at each occurrence, is independently selected from N, O, S, S(=O), and S(=O) ２ and containing 1, 2, 3, or 4 heteroatoms selected from each heteroaryl group, at each occurrence, contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S; A compound, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof.

2. R １ is hydrogen, deuterium, halogen, -CN, -OC １－６ alkyl group, -C １－６ Alkyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, —C ２－６ Alkenyl group, —C ２－６ an alkynyl group or a 3- to 6-membered cycloalkyl group, １－６ alkyl group, -C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ The alkynyl group or the 3- to 6-membered cycloalkyl group may be unsubstituted or may be substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; The compound of claim 1.

3. R １ represents hydrogen, deuterium, -F, -Cl, -Br, -CN, -OCH ３ , -CF ３ , -CH ２ CH ２ CN, a methyl group, an ethyl group, or a cyclopropyl group; The compound of claim 2.

4. X １ may, in each occurrence, independently represent -C(R Ｘ１１ ) (R Ｘ１２ ) -, -NR Ｘ１３ -, -O-, -S-, or -S(=O)-; R Ｘ１１ or R Ｘ１２ are independently hydrogen, deuterium, halogen, -C １－６ an alkyl group or a 3- to 6-membered cycloalkyl group, １－６ The alkyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; Optionally, R Ｘ１１ and R Ｘ１２ together with the carbon atoms bonded to both of these, 【Transformation 38】 wherein the above-mentioned 【Chemistry 39】 are independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; R Ｘ１３ is hydrogen, deuterium, -C １－６ an alkyl group or a 3- to 6-membered cycloalkyl group, １－６ The alkyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; The compound according to any one of claims 1 to 3.

5. R Ｘ１１ or R Ｘ１２ are independently hydrogen, deuterium, -F, a methyl group, or -CD ３ , an ethyl group, a propyl group, an isopropyl group, or a cyclopropyl group; Optionally, R Ｘ１１ and R Ｘ１２ together with the carbon atoms bonded to both of these, 【Chemistry 40】 Forming R Ｘ１３ are independently hydrogen, deuterium, a methyl group, -CD ３ , an ethyl group, a propyl group, an isopropyl group, or a cyclopropyl group; The compound of claim 4.

6. R Ｓ２ is deuterium, halogen, or -C １－６ alkyl group, wherein the above-mentioned —C １－６ The alkyl groups are independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; Optionally, two adjacent R Ｓ２ along with the atoms to which they are bonded, 【Chemistry 41】 forming a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, a benzene ring, or a 5- to 6-membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; The compound according to any one of claims 1 to 5.

7. R Ｓ２ is deuterium, -F, -CH ３ , or -CD ３ That is, The compound of claim 6.

8. m １ is 0, 1, 2, 3, 4, 5, or 6; The compound according to any one of claims 1 to 7.

9. R Ｓ１ is deuterium, halogen, -C １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ Alkynyl group, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, —OC １－６ an alkyl group or a 3- to 6-membered cycloalkyl group, １－６ alkyl group, -C ２－６ Alkenyl group, —C ２－６ The alkynyl group or the 3- to 6-membered cycloalkyl group is independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; Optionally, two R Ｓ１ together with the carbon atoms bonded to both of these, 【Chemistry 42】 or forms a 3- to 6-membered carbocyclic ring, 【Chemistry 43】 The 3- to 6-membered carbocyclic rings are independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; R ｂ is -C １－６ is an alkyl group, Optionally, two adjacent R Ｓ１ along with the atoms to which they are bonded, 【Chemistry 44】 or form a 3- to 6-membered carbocyclic ring, wherein said 3- to 6-membered carbocyclic ring is independently unsubstituted or substituted with deuterium, halogen, halogenated C １－６ Alkyl group, halogenated C １－６ Alkoxy group, -CN, -NH ２ , —NH(C １－６ alkyl group), -N(C １－６ alkyl group) ２ , —OH, and —OC １－６ substituted with 1, 2, or 3 substituents selected from alkyl groups; The compound according to any one of claims 1 to 8.

10. R Ｓ１ is -F, -OH, -OCH ３ , -CN, -CH ２ F, -CF ３ , -CH ２ OCH ３ , -CH ２ CN, -CHF ２ , -CD ３ , -NH ２ , or -CH ３ or two R Ｓ１ together with the carbon atoms bonded to both of these, 【Chemistry 45】 or a cyclopropyl ring, or two adjacent R Ｓ１ together with the atoms to which they are attached form a cyclopropyl ring, The compound of claim 9.

11. The compound is any of the compounds described in Table A of the specification. The compound according to any one of claims 1 to 10.

12. The compound is any of the compounds described in Table B of the specification. The compound according to any one of claims 1 to 11.

13. Y １ is O, The compound according to any one of claims 1 to 12. 【Request Item 14】 【Chemistry 46】 teeth, 【Chemistry 47】 and 【Chemistry 48】 teeth, 【Chemistry 49】 and R Ｓ３８１ is hydrogen or R Ｓ３８ and m ８１ is 0, 1, 2, 3, 4, 5, 6, 7, or 8, [Transformation 50] teeth, 【Chemistry 51】 and wherein ring L is a 4-6 membered heterocycle, optionally further containing 1 or 2 heteroatoms selected from N and O; The compound according to any one of claims 1 to 13. 【Request Item 15】 【Chemistry 52】 teeth, 【Chemistry 53】 【Chemistry 54】 That is, The compound according to any one of claims 1 to 14.

16. R ４ teeth, 【Transformation 55】 【Transformation 56】 and m ７ is 0, 1, 2, or 3, R Ｓ４ａ is —OH or —NH ２ and R Ｓ４ｂ is hydrogen, deuterium, or a halogen, R Ｓ４ｃ is hydrogen, deuterium, -C １－３ alkyl group, -C ２－３ alkenyl group, or —C ２－３ is an alkynyl group, R Ｓ４ｄ is hydrogen, deuterium, or a halogen, R Ｓ４ｅ is hydrogen, deuterium, halogen, -C １－３ Alkyl group or halogenated C １－３ is an alkyl group, R Ｓ４ｆ is —OH or —NH ２ and R Ｓ４ｇ is hydrogen, deuterium, halogen, -C １－３ Alkyl group or halogenated C １－３ is an alkyl group, R Ｓ４ｈ is hydrogen, deuterium, halogen, -C １－３ Alkyl group or halogenated C １－３ is an alkyl group, R Ｓ４ｉ is hydrogen, deuterium, halogen, -C １－３ Alkyl group or halogenated C １－３ is an alkyl group, R Ｓ４ｊ is hydrogen, deuterium, halogen, -CN, -C １－３ Alkyl group, halogenated C １－３ Alkyl group, or -O halogenated C １－３ is an alkyl group, R Ｓ４ｋ is hydrogen, deuterium, halogen, -CN, -C １－３ Alkyl group, halogenated C １－３ Alkyl group, or -O halogenated C １－３ is an alkyl group, R Ｓ４ｌ is hydrogen, deuterium, halogen, -CN, -C １－３ Alkyl group, halogenated C １－３ Alkyl group, or -O halogenated C １－３ is an alkyl group, R Ｓ４ｍ is hydrogen, deuterium, halogen, -CN, -C １－３ Alkyl group, halogenated C １－３ Alkyl group, or -O halogenated C １－３ is an alkyl group, R Ｓ４ｎ is hydrogen, deuterium, halogen, -C １－３ Alkyl group or halogenated C １－３ is an alkyl group, R Ｓ４ｏ is hydrogen, deuterium, halogen, -C １－３ Alkyl group or halogenated C １－３ is an alkyl group, R Ｓ４ｐ is hydrogen, deuterium, halogen, -C １－３ Alkyl group or halogenated C １－３ is an alkyl group, The compound according to any one of claims 1 to 15.

17. R ４ teeth, 【Chemistry 57】 【Transformation 58】 That is, 17. The compound of claim 16.

18. R ５ is a halogen, The compound according to any one of claims 1 to 17.

19. R ５ is -F, 19. The compound of claim 18.

20. The compound is any of the compounds in Table C of the specification. The compound of claim 1.

21. a therapeutically effective amount of a compound of formula (I) according to any one of claims 1 to 20, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, and a pharmaceutically acceptable excipient. Pharmaceutical compositions.

22. 22. A method for treating a rheumatoid arthritis comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) according to any one of claims 1 to 20, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of said stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition according to claim 21. A method of treating cancer in a subject.

23. the cancer is pancreatic cancer, colorectal cancer, lung cancer (e.g., non-small cell lung cancer), breast cancer, colon cancer, gastric cancer, endometrial cancer, esophageal cancer, or gastroesophageal junction cancer; 23. The method of claim 22.

24. the cancer is associated with at least one of K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-Ras G12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutation, and / or K-Ras wild-type amplification; 24. The method of claim 23. 【Request Item 25】 【Chemistry 59】 An intermediate having the structure L １ is -Cl, -Br, -S(=O)CH ３ , or -S(=O) ２ CH ３ and L ２ is —Cl or —Br, Ring A, R Ｓ１ , m １ , R Ｓ２ , m ２ , n １ , X １ , X ２ , R ５ , Y １ , R ３ The definition of is the same as that of any one of claims 1 to 20. Intermediate.

26. The intermediate is any intermediate in Table D.

26. The intermediate of claim 25.

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