Naphthyridine compounds as inhibitors of KRAS

Abstract

Disclosed are compounds of formula (I), methods of using the compounds to inhibit KRAS activity, and pharmaceutical compositions containing such compounds, which are useful for treating, preventing, or ameliorating diseases or disorders associated with KRAS activity, such as cancer.

Description

[Technical field]

[0001] Related Applications This application claims priority to U.S. Provisional Application No. 63 / 239,152, filed August 31, 2021, and U.S. Provisional Application No. 63 / 364,593, filed May 12, 2022, the contents of which are incorporated by reference in their entireties herein.

[0002] The present disclosure provides compounds, as well as compositions and methods of use thereof, that modulate KRAS activity and are useful in the treatment of a variety of diseases, including cancer. [Background technology]

[0003] Ras proteins are part of a family of small GTPases that are activated by growth factors and various extracellular stimuli. The Ras family regulates intracellular signaling pathways that are involved in cell growth, migration, survival, and differentiation. Activation of RAS proteins in the cell membrane leads to the binding of key effectors and the initiation of a cascade of intracellular signaling pathways within the cell, including the RAF and PI3K kinase pathways. Somatic mutations in RAS can lead to uncontrolled cell growth and malignant transformation, while activation of RAS proteins is tightly regulated in normal cells (Simanshu, D. et al. Cell 170.1 (2017): 17-33).

[0004] The Ras family consists of three members: KRAS, NRAS, and HRAS. RAS-mutated cancers account for approximately 25% of human cancers. KRAS is the most frequently mutated isoform, accounting for 85% of all RAS mutations, while NRAS and HRAS are mutated in 12% and 3% of all RAS-mutated cancers, respectively (Simanshu, D. et al. Cell 170.1 (2017): 17-33). KRAS mutations are prevalent among the top three most lethal types of cancer: pancreatic (97%), colorectal (44%), and lung (30%) (Cox, AD et al. Nat Rev Drug Discov (2014) 13: 828-51). The majority of RAS mutations occur at amino acid residues 12, 13, and 61. The frequency of certain mutations varies between RAS gene isoforms, with G12 and Q61 mutations predominating in KRAS and NRAS, respectively, and G12, G13 and Q61 mutations occurring most frequently in HRAS. Furthermore, the spectrum of mutations in RAS isoforms differs between cancer types. For example, KRAS G12D mutations predominate in pancreatic cancer (51%), followed by colorectal adenocarcinoma (45%) and lung cancer (17%), while KRAS G12V mutations are associated with pancreatic cancer (30%), followed by colorectal adenocarcinoma (27%) and lung adenocarcinoma (23%) (Cox, AD et al. Nat Rev Drug Discov (2014) 13:828-51). In contrast, KRAS G12C mutations predominate in non-small cell lung cancer (NSCLC), accounting for 11-16% of lung adenocarcinomas and 2-5% of pancreatic and colorectal adenocarcinomas (Cox, AD et al. Nat. Rev. Drug Discov. (2014) 13:828-51). Genomic studies across hundreds of cancer cell lines have demonstrated that cancer cells containing KRAS mutations are highly dependent on KRAS function for cell growth and survival (McDonald, R. et al. Cell 170 (2017):577-592).The role of mutant KRAS as an oncogenic driver is further supported by extensive in vivo experimental evidence showing that mutant KRAS is required for the initiation and maintenance of initial tumors in animal models (Cox, AD et al. Nat Rev Drug Discov (2014) 13:828-51).

[0005] Taken together, these findings suggest that KRAS mutations play an important role in human cancer; therefore, the development of inhibitors targeting mutant KRAS may be useful in the clinical treatment of diseases characterized by KRAS mutations. Summary of the Invention

[0006] The present disclosure relates, inter alia, to a compound of formula I: [ka] or a pharma- ceutically acceptable salt thereof, wherein the constituent variables are as defined herein.

[0007] The present disclosure further provides a pharmaceutical composition comprising a compound of the present disclosure, or a pharma- ceutically acceptable salt thereof, and at least one pharma- ceutically acceptable carrier or excipient.

[0008] The present disclosure further provides a method for inhibiting KRAS activity, comprising administering to an individual a compound of the present disclosure or a pharma- ceutically acceptable salt thereof.The present disclosure also provides the use of the compound described herein in the manufacture of a medicament for use in a therapeutic method.The present disclosure also provides the compound described herein for use in a therapeutic method.

[0009] The present disclosure further provides a method of treating a disease or disorder in a patient, comprising administering to the patient a therapeutically effective amount of a compound of the present disclosure, or a pharma- ceutically acceptable salt thereof. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] compound In one aspect, the present disclosure provides a compound of formula I: [ka] or a pharma- ceutically acceptable salt thereof, wherein: [ka] represents a single or double bond; -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 H, D, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , S.R. a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , O.C.(O)R b1 , O-C(O)NR c1 R d1 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)OR a1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 S(O)R b1 , N.R. c1 S(O) 2 R b1 , N.R. c1 S(O)2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , S(O) 2 NR c1 R d1 , and B.R. h1 R i1 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from R 2 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a2 , S.R. a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , O.C.(O)R b2 , O-C(O)NR c2 R d2 , N.R. c2 R d2 , N.R. c2 C(O)R b2 , N.R. c2C(O)OR a2 , N.R. c2 C(O)NR c2 R d2 , C(=NR e2 )R b2 , C(=NOR a2 )R b2 , C(=NR e2 )NR c2 R d2 , N.R. c2 C(=NR e2 )NR c2 R d2 , N.R. c2 C(=NR e2 )R b2 , N.R. c2 S(O)R b2 , N.R. c2 S(O) 2 R b2 , N.R. c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , S(O) 2 NR c2 R d2 , and B.R. h2 R i2 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 23 substituted with 1, 2, 3, or 4 substituents independently selected from Cy 1 is C 3~10Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 10 substituted with 1, 2, 3, or 4 substituents independently selected from R 4 teeth, [ka] when is a single bond, is selected from =O and =S; R 3 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 alkylene; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 30 substituted with 1, 2, 3, or 4 substituents independently selected from R 3 teeth, [ka] is absent when is a double bond; R 4 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a3 , S.R. a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , O.C.(O)R b3 , O-C(O)NR c3 R d3 , N.R. c3 R d3 , N.R. c3 C(O)R b3 , N.R. c3 C(O)OR a3 , N.R. c3 C(O)NR c3 R d3 , C(=NR e3 )Rb3 , C(=NOR a3 )R b3 , C(=NR e3 )NR c3 R d3 , N.R. c3 C(=NR e3 )NR c3 R d3 , N.R. c3 C(=NR e3 )R b3 , N.R. c3 S(O)R b3 , N.R. c3 S(O) 2 R b3 , N.R. c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , S(O) 2 NR c3 R d3 , and B.R. h3 R i3 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 30 substituted with 1, 2, 3, or 4 substituents independently selected from R 5 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a5 , S.R. a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , O.C.(O)R b5 , O-C(O)NR c5 R d5 , N.R. c5 R d5 , N.R. c5 C(O)R b5 , N.R. c5 C(O)OR a5 , N.R. c5 C(O)NR c5 R d5 , C(=NR e5 )R b5 , C(=NOR a5 )R b5 , C(=NR e5 )NR c5 R d5 , N.R. c5 C(=NR e5 )NR c5 R d5 , N.R. c5 C(=NR e5 )R b5 , N.R. c5 S(O)R b5 , N.R. c5 S(O) 2 R b5 , N.R. c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5, S(O) 2 NR c5 R d5 , and B.R. h5 R i5 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from R 6 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a6 , S.R. a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , O.C.(O)R b6 , O-C(O)NR c6 R d6 , N.R. c6 R d6 , N.R. c6 C(O)Rb6 , N.R. c6 C(O)OR a6 , N.R. c6 C(O)NR c6 R d6 , C(=NR e6 )R b6 , C(=NOR a6 )R b6 , C(=NR e6 )NR c6 R d6 , N.R. c6 C(=NR e6 )NR c6 R d6 , N.R. c6 C(=NR e6 )R b6 , N.R. c6 S(O)R b6 , N.R. c6 S(O) 2 R b6 , N.R. c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , S(O) 2 NR c6 R d6 , and B.R. h6 R i6 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 60 substituted with 1, 2, 3, or 4 substituents independently selected from R7 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a7 , S.R. a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , O.C.(O)R b7 , O-C(O)NR c7 R d7 , N.R. c7 R d7 , N.R. c7 C(O)R b7 , N.R. c7 C(O)OR a7 , N.R. c7 C(O)NR c7 R d7 , C(=NR e7 )R b7 , C(=NOR a7 )R b7 , C(=NR e7 )NR c7 R d7 , N.R. c7 C(=NR e7 )NR c7 R d7 , N.R. c7 C(=NR e7 )R b7 , N.R. c7 S(O)R b7 , N.R. c7 S(O) 2 R b7 , N.R. c7 S(O) 2 NRc7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , S(O) 2 NR c7 R d7 , and B.R. h7 R i7 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 70 substituted with 1, 2, 3, or 4 substituents independently selected from Cy 2 is C 3~10 Cycloalkyl, 4-14 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 5-10 membered heteroaryl and 4-14 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-14 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 20 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 10 is C1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a10 , S.R. a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , O.C.(O)R b10 , O-C(O)NR c10 R d10 , N.R. c10 R d10 , N.R. c10 C(O)R b10 , N.R. c10 C(O)OR a10 , N.R. c10 C(O)NR c10 R d10 , C(=NR e10 )R b10 , C(=NOR a10 )R b10 , C(=NR e10 )NR c10 R d10 , N.R. c10 C(=NR e10 )NR c10 R d10 , N.R. c10 S(O)R b10 , N.R. c10 S(O) 2 R b10 , N.R. c10 S(O) 2 NR c10 R d10 , S(O)R b10 , S(O)NR c10 Rd10 , S(O) 2 R b10 , S(O) 2 NR c10 R d10 , and B.R. h10 R i10 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 11 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 11 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a11 , S.R. a11 , C(O)R b11 , C(O)NR c11 R d11 , C(O)OR a11 , O.C.(O)R b11 , O-C(O)NR c11 R d11 , N.R. c11 Rd11 , N.R. c11 C(O)R b11 , N.R. c11 C(O)OR a11 , N.R. c11 C(O)NR c11 R d11 , N.R. c11 S(O)R b11 , N.R. c11 S(O) 2 R b11 , N.R. c11 S(O) 2 NR c11 R d11 , S(O)R b11 , S(O)NR c11 R d11 , S(O) 2 R b11 , S(O) 2 NR c11 R d11 , and B.R. h11 R i11 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 12 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 12 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a12 , S.R. a12, C(O)R b12 , C(O)NR c12 R d12 , C(O)OR a12 , O.C.(O)R b12 , O-C(O)NR c12 R d12 , N.R. c12 R d12 , N.R. c12 C(O)R b12 , N.R. c12 C(O)OR a12 , N.R. c12 C(O)NR c12 R d12 , N.R. c12 S(O)R b12 , N.R. c12 S(O) 2 R b12 , N.R. c12 S(O) 2 NR c12 R d12 , S(O)R b12 , S(O)NR c12 R d12 , S(O) 2 R b12 , S(O) 2 NR c12 R d12 , and B.R. h12 R i12 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from Each R 20 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a20 , S.R. a20 , C(O)R b20 , C(O)NR c20 R d20 , C(O)OR a20 , O.C.(O)R b20 , O-C(O)NR c20 R d20 , N.R. c20 R d20 , N.R. c20 C(O)R b20 , N.R. c20 C(O)OR a20 , N.R. c20 C(O)NR c20 R d20 , C(=NR e20 )R b20 , C(=NOR a20 )R b20 , C(=NR e20 )NR c20 R d20 , N.R. c20 C(=NR e20 )NR c20 R d20 , N.R. c20 S(O)R b20 , N.R. c20 S(O) 2 R b20 , N.R. c20 S(O) 2 NR c20 R d20 , S(O)R b20 , S(O)NR c20 R d20 , S(O) 2 R b20 , S(O) 2 NR c20 R d20 , and B.R. h20 R i20 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 21 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 21 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a21 , S.R. a21 , C(O)R b21 , C(O)NR c21 R d21 , C(O)OR a21 , O.C.(O)R b21 , O-C(O)NR c21 R d21 , N.R. c21 R d21 , N.R. c21 C(O)R b21 , N.R. c21 C(O)OR a21 , N.R. c21 C(O)NR c21 R d21 , N.R. c21 S(O)R b21 , N.R. c21 S(O)2 R b21 , N.R. c21 S(O) 2 NR c21 R d21 , S(O)R b21 , S(O)NR c21 R d21 , S(O) 2 R b21 , S(O) 2 NR c21 R d21 , and B.R. h21 R i21 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 22 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 22 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a22 , S.R. a22 , C(O)R b22 , C(O)NR c22 R d22 , C(O)OR a22 , O.C.(O)R b22 , O-C(O)NR c22 R d22 , N.R. c22 R d22 , N.R. c22 C(O)R b22, N.R. c22 C(O)OR a22 , N.R. c22 C(O)NR c22 R d22 , N.R. c22 S(O)R b22 , N.R. c22 S(O) 2 R b22 , N.R. c22 S(O) 2 NR c22 R d22 , S(O)R b22 , S(O)NR c22 R d22 , S(O) 2 R b22 , S(O) 2 NR c22 R d22 , and B.R. h22 R i22 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from Each R 23 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a23 , S.R. a23 , C(O)R b23 , C(O)NRc23 R d23 , C(O)OR a23 , O.C.(O)R b23 , O-C(O)NR c23 R d23 , N.R. c23 R d23 , N.R. c23 C(O)R b23 , N.R. c23 C(O)OR a23 , N.R. c23 C(O)NR c23 R d23 , N.R. c23 S(O)R b23 , N.R. c23 S(O) 2 R b23 , N.R. c23 S(O) 2 NR c23 R d23 , S(O)R b23 , S(O)NR c23 R d23 , S(O) 2 R b23 , S(O) 2 NR c23 R d23 , and B.R. h23 R i23 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 24 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 24 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C1~6 Haloalkyl, C 3~6 Cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a24 , S.R. a24 , C(O)R b24 , C(O)NR c24 R d24 , C(O)OR a24 , O.C.(O)R b24 , O-C(O)NR c24 R d24 , N.R. c24 R d24 , N.R. c24 C(O)R b24 , N.R. c24 C(O)OR a24 , N.R. c24 C(O)NR c24 R d24 , N.R. c24 S(O)R b24 , N.R. c24 S(O) 2 R b24 , N.R. c24 S(O) 2 NR c24 R d24 , S(O)R b24 , S(O)NR c24 R d24 , S(O) 2 R b24 , S(O) 2 NR c24 R d24 , and B.R. h24 R i24 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from Each R 30 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a30 , S.R. a30 , C(O)R b30 , C(O)NR c30 R d30 , C(O)OR a30 , O.C.(O)R b30 , O-C(O)NR c30 R d30 , N.R. c30 R d30 , N.R. c30 C(O)R b30 , N.R. c30 C(O)OR a30 , N.R. c30 C(O)NR c30 R d30 , N.R. c30 S(O)R b30 , N.R. c30 S(O) 2 R b30 , N.R. c30 S(O) 2 NR c30 R d30 , S(O)R b30 , S(O)NR c30 R d30 , S(O) 2 R b30 , S(O) 2 NR c30 R d30 , and B.R. h30 R i30 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 31 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a31 , S.R. a31 , C(O)R b31 , C(O)NR c31 R d31 , C(O)OR a31 , O.C.(O)R b31 , O-C(O)NR c31 R d31 , N.R. c31 R d31 , N.R. c31 C(O)R b31 , N.R. c31 C(O)OR a31 , N.R. c31 C(O)NR c31 R d31 , N.R. c31 S(O)R b31 , N.R. c31 S(O) 2 R b31 , N.R. c31 S(O) 2 NRc31 R d31 , S(O)R b31 , S(O)NR c31 R d31 , S(O) 2 R b31 , S(O) 2 NR c31 R d31 , and B.R. h31 R i31 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 32 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 32 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a32 , S.R. a32 , C(O)R b32 , C(O)NR c32 R d32 , C(O)OR a32 , O.C.(O)R b32 , O-C(O)NR c32 R d32 , N.R. c32 R d32 , N.R. c32 C(O)R b32 , N.R. c32 C(O)OR a32 , N.R. c32 C(O)NRc32 R d32 , N.R. c32 S(O)R b32 , N.R. c32 S(O) 2 R b32 , N.R. c32 S(O) 2 NR c32 R d32 , S(O)R b32 , S(O)NR c32 R d32 , S(O) 2 R b32 , S(O) 2 NR c32 R d32 , and B.R. h32 R i32 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from Each R 60 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a60 , S.R. a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , O.C.(O)R b60, O-C(O)NR c60 R d60 , N.R. c60 R d60 , N.R. c60 C(O)R b60 , N.R. c60 C(O)OR a60 , N.R. c60 C(O)NR c60 R d60 , N.R. c60 S(O)R b60 , N.R. c60 S(O) 2 R b60 , N.R. c60 S(O) 2 NR c60 R d60 , S(O)R b60 , S(O)NR c60 R d60 , S(O) 2 R b60 , S(O) 2 NR c60 R d60 , and B.R. h60 R i60 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 61 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 61 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a61 , S.R. a61 , C(O)R b61 , C(O)NR c61 R d61 , C(O)OR a61 , O.C.(O)R b61 , O-C(O)NR c61 R d61 , N.R. c61 R d61 , N.R. c61 C(O)R b61 , N.R. c61 C(O)OR a61 , N.R. c61 C(O)NR c61 R d61 , N.R. c61 S(O)R b61 , N.R. c61 S(O) 2 R b61 , N.R. c61 S(O) 2 NR c61 R d61 , S(O)R b61 , S(O)NR c61 R d61 , S(O) 2 R b61 , S(O) 2 NR c61 R d61 , and B.R. h61 R i61 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 62 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 62 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a62 , S.R. a62 , C(O)R b62 , C(O)NR c62 R d62 , C(O)OR a62 , O.C.(O)R b62 , O-C(O)NR c62 R d62 , N.R. c62 R d62 , N.R. c62 C(O)R b62 , N.R. c62 C(O)OR a62 , N.R. c62 C(O)NR c62 R d62 , N.R. c62 S(O)R b62 , N.R. c62 S(O) 2 R b62 , N.R. c62 S(O) 2 NR c62 R d62 , S(O)R b62 , S(O)NR c62 R d62 , S(O) 2 R b62 , S(O) 2 NR c62 R d62 , and B.R. h62 R i62 Independently selected from the above C 1~6 Alkyl, C2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from Each R 70 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a70 , S.R. a70 , C(O)R b70 , C(O)NR c70 R d70 , C(O)OR a70 , O.C.(O)R b70 , O-C(O)NR c70 R d70 , N.R. c70 R d70 , N.R. c70 C(O)R b70 , N.R. c70 C(O)OR a70 , N.R. c70 C(O)NR c70 R d70 , N.R. c70 S(O)R b70 , N.R. c70 S(O) 2 R b70 , N.R. c70 S(O) 2 NR c70 R d70 , S(O)R b70 , S(O)NR c70 Rd70 , S(O) 2 R b70 , S(O) 2 NR c70 R d70 , and B.R. h70 R i70 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from R a1 , R b1 , R c1 , and R d1 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R g or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c1 and R d1together with the N atom to which they are attached, R g forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h1 and R i1 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h1 and R i1 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a2 , R b2 , R c2 , and R d2 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 23 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c2 and R d2 together with the N atom to which they are attached, R 23 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e2 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h2 and R i2 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h2 and R i2 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a3 , R b3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10Aryl and 5-10 membered heteroaryl are each optionally represented by R 30 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c3 and R d3 together with the N atom to which they are attached, R 30 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e3 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h3 and R i3 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h3 and R i3 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a5 , R b5 , R c5 , and R d5 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R g or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c5 and R d5 together with the N atom to which they are attached, R g forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R e5 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h5 and R i5 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h5 and R i5together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a6 , R b6 , R c6 , and R d6 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 60 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c6 and R d6 together with the N atom to which they are attached, R 60 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R e6 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h6 and R i6 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h6 and R i6 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a7 , R b7 , R c7 , and R d7 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 70 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c7 and R d7 together with the N atom to which they are attached, R 70 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each Re7 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h7 and R i7 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h7 and R i7 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a10 , R b10 , R c10 , and R d10 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10Aryl and 5-10 membered heteroaryl are each optionally represented by R 11 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c10 and R d10 together with the N atom to which they are attached, R 11 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e10 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h10 and R i10 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h10 and R i10 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a11 , R b11 , R c11 , and R d11 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R 12 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c11 and R d11 together with the N atom to which they are attached, R 12 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h11 and R i11 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h11 and R i11 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a12 , R b12 , R c12 , and R d12 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R gsubstituted with 1, 2, 3, or 4 substituents independently selected from R h12 and R i12 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h12 and R i12 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a20 , R b20 , R c20 , and R d20 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 21 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c20 and R d20 together with the N atom to which they are attached, R 21 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e20 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h20 and R i20 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h20 and R i20 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a21 , R b21 , R c21 , and R d21 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R 22 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atomc21 and R d21 together with the N atom to which they are attached, R 22 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h21 and R i21 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h21 and R i21 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a22 , R b22 , R c22 , and R d22 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from R h22 and R i22 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h22 and R i22 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a23 , R b23 , R c23 , and R d23 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R 24 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c23 and R d23 together with the N atom to which they are attached, R 24 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h23 and R i23 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h23 and R i23 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a24 , R b24 , R c24 , and R d24 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from R h24 and R i24 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h24 and R i24 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a30 , R b30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 31 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c30 and R d30 together with the N atom to which they are attached, R 31forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R h30 and R i30 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h30 and R i30 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a31 , R b31 , R c31 , and R d31 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R 32 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c31 and R d31 together with the N atom to which they are attached, R 32 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h31 and R i31 are OH and C, respectively. 1~6 Alkoxy and C1~6 haloalkoxy, or any R bonded to the same B atom h31 and R i31 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a32 , R b32 , R c32 , and R d32 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R g or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c32 and R d32 together with the N atom to which they are attached, R g forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R h32 and R i32 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h32 and R i32 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a60 , R b60 , Rc60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 61 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c60 and R d60 together with the N atom to which they are attached, R 61 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R h60 and R i60 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h60 and R i60 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a61 , R b61 , R c61 , and R d61 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6Haloalkyl, C 3~6 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R 62 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c61 and R d61 together with the N atom to which they are attached, R 62 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h61 and R i61 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h61 and R i61 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a62 , R b62 , R c62 , and R d62 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R g or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c62 and R d62 together with the N atom to which they are attached, R g forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R h62 and R i62 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h62 and R i62 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a70 , R b70 , R c70 , and R d70 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R g or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c70 and R d70 together with the N atom to which they are attached, R gforming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R h70 and R i70 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h70 and R i70 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; Each R g D, OH, NO 2 ,CN,Haro,C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, C 3~6 Cycloalkyl-C 1~2 Alkylene, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 1~3 Alkoxy-C 1~3 Alkyl, C 1~3 Alkoxy-C 1~3 Alkoxy, HO-C 1~3 Alkoxy, HO-C 1~3 Alkyl, Cyano-C 1~3 Alkyl, H 2 NC 1~3 Alkyl, Amino, C 1~6 Alkylamino, di(C 1~6 Alkyl)amino, thio, C 1~6 Alkylthio, C 1~6 Alkylsulfinyl, C 1~6 Alkyl sulfonyl, carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl) carbamyl, carboxy, C 1~6 Alkyl carbonyl, C 1~6Alkoxycarbonyl, C 1~6 Alkylcarbonylamino, C 1~6 Alkoxycarbonylamino, C 1~6 Alkylcarbonyloxy, aminocarbonyloxy, C 1~6 Alkylaminocarbonyloxy, di(C 1~6 Alkyl)aminocarbonyloxy, C 1~6 Alkyl sulfonylamino, aminosulfonyl, C 1~6 Alkylaminosulfonyl, di(C 1~6 Alkyl)aminosulfonyl, aminosulfonylamino, C 1~6 Alkylaminosulfonylamino, di(C 1~6 Alkyl)aminosulfonylamino, aminocarbonylamino, C 1~6 Alkylaminocarbonylamino, and di(C 1~6 alkyl)aminocarbonylamino; however, (a) Cy 1 is other than 3,5-dimethylisoxazol-4-yl; (b)R 3 is CH 2 CF 3 It is unexpected.

[0011] In one embodiment of Formula I or a pharma- ceutically acceptable salt thereof, [ka] represents a single or double bond; -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 H, D, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , S.R. a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , O.C.(O)R b1 , O-C(O)NR c1 R d1 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)OR a1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 S(O)R b1 , N.R. c1 S(O) 2 R b1 , N.R. c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , S(O) 2 NR c1 R d1 , and B.R. h1 R i1 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from R 2 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a2 , S.R. a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , O.C.(O)R b2 , O-C(O)NR c2 R d2 , N.R. c2 R d2 , N.R. c2 C(O)R b2 , N.R. c2 C(O)OR a2 , N.R. c2 C(O)NR c2 R d2 , C(=NR e2 )R b2 , C(=NOR a2 )R b2 , C(=NR e2 )NR c2 R d2 , N.R. c2 C(=NR e2 )NR c2 R d2 , N.R. c2 C(=NR e2 )R b2 , N.R. c2 S(O)R b2 , N.R. c2 S(O) 2 R b2 , N.R. c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O)2 R b2 , S(O) 2 NR c2 R d2 , and B.R. h2 R i2 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 23 substituted with 1, 2, 3, or 4 substituents independently selected from Cy 1 is C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 6-10 membered heteroaryl and 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 substituted with 1, 2, 3, or 4 substituents independently selected from R 4 teeth, [ka] when is a single bond, is selected from =O and =S; R 3 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 alkylene; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 30 substituted with 1, 2, 3, or 4 substituents independently selected from R 3 teeth, [ka] is absent when is a double bond; R 4 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a3 , S.R. a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , O.C.(O)R b3 , O-C(O)NR c3 R d3 , N.R. c3 R d3 , N.R. c3 C(O)R b3 , N.R. c3 C(O)OR a3 , N.R. c3 C(O)NR c3 R d3 , C(=NR e3 )R b3 , C(=NOR a3 )R b3 , C(=NR e3 )NR c3 R d3 , N.R. c3 C(=NR e3 )NR c3 R d3 , N.R. c3 C(=NR e3 )R b3 , N.R. c3 S(O)R b3 , N.R. c3 S(O) 2 R b3 , N.R. c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , S(O) 2 NR c3 R d3 , and B.R.h3 R i3 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 30 substituted with 1, 2, 3, or 4 substituents independently selected from R 5 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a5 , S.R. a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , O.C.(O)R b5 , O-C(O)NR c5 R d5 , N.R. c5 R d5 , N.R. c5 C(O)R b5 , N.R. c5 C(O)OR a5 , N.R.c5 C(O)NR c5 R d5 , C(=NR e5 )R b5 , C(=NOR a5 )R b5 , C(=NR e5 )NR c5 R d5 , N.R. c5 C(=NR e5 )NR c5 R d5 , N.R. c5 C(=NR e5 )R b5 , N.R. c5 S(O)R b5 , N.R. c5 S(O) 2 R b5 , N.R. c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , S(O) 2 NR c5 R d5 , and B.R. h5 R i5 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R g substituted with 1, 2, 3, or 4 substituents independently selected from R 6 , H, C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a6 , S.R. a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , O.C.(O)R b6 , O-C(O)NR c6 R d6 , N.R. c6 R d6 , N.R. c6 C(O)R b6 , N.R. c6 C(O)OR a6 , N.R. c6 C(O)NR c6 R d6 , C(=NR e6 )R b6 , C(=NOR a6 )R b6 , C(=NR e6 )NR c6 R d6 , N.R. c6 C(=NR e6 )NR c6 R d6 , N.R. c6 C(=NR e6 )R b6 , N.R. c6 S(O)R b6 , N.R. c6 S(O) 2 R b6 , N.R. c6 S(O) 2 NR c6 R d6 , S(O)R b6, S(O)NR c6 R d6 , S(O) 2 R b6 , S(O) 2 NR c6 R d6 , and B.R. h6 R i6 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 60 substituted with 1, 2, 3, or 4 substituents independently selected from R 7 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a7 , S.R. a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , O.C.(O)R b7 , O-C(O)NR c7 Rd7 , N.R. c7 R d7 , N.R. c7 C(O)R b7 , N.R. c7 C(O)OR a7 , N.R. c7 C(O)NR c7 R d7 , C(=NR e7 )R b7 , C(=NOR a7 )R b7 , C(=NR e7 )NR c7 R d7 , N.R. c7 C(=NR e7 )NR c7 R d7 , N.R. c7 C(=NR e7 )R b7 , N.R. c7 S(O)R b7 , N.R. c7 S(O) 2 R b7 , N.R. c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , S(O) 2 NR c7 R d7 , and B.R. h7 R i7 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3Each alkylene is optionally represented by R 70 substituted with 1, 2, 3, or 4 substituents independently selected from Cy 2 is C 3~10 Cycloalkyl, 4-14 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 5-10 membered heteroaryl and 4-14 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-14 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 20 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 10 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a10 , S.R. a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , O.C.(O)R b10 , O-C(O)NR c10 Rd10 , N.R. c10 R d10 , N.R. c10 C(O)R b10 , N.R. c10 C(O)OR a10 , N.R. c10 C(O)NR c10 R d10 , C(=NR e10 )R b10 , C(=NOR a10 )R b10 , C(=NR e10 )NR c10 R d10 , N.R. c10 C(=NR e10 )NR c10 R d10 , N.R. c10 S(O)R b10 , N.R. c10 S(O) 2 R b10 , N.R. c10 S(O) 2 NR c10 R d10 , S(O)R b10 , S(O)NR c10 R d10 , S(O) 2 R b10 , S(O) 2 NR c10 R d10 , and B.R. h10 R i10 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 11substituted with 1, 2, 3, or 4 substituents independently selected from Each R 11 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a11 , S.R. a11 , C(O)R b11 , C(O)NR c11 R d11 , C(O)OR a11 , O.C.(O)R b11 , O-C(O)NR c11 R d11 , N.R. c11 R d11 , N.R. c11 C(O)R b11 , N.R. c11 C(O)OR a11 , N.R. c11 C(O)NR c11 R d11 , N.R. c11 S(O)R b11 , N.R. c11 S(O) 2 R b11 , N.R. c11 S(O) 2 NR c11 R d11 , S(O)R b11 , S(O)NR c11 R d11 , S(O) 2 R b11 , S(O) 2 NR c11 R d11 , and B.R. h11 R i11 are independently selected from; Each R 20 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a20 , S.R. a20 , C(O)R b20 , C(O)NR c20 R d20 , C(O)OR a20 , O.C.(O)R b20 , O-C(O)NR c20 R d20 , N.R. c20 R d20 , N.R. c20 C(O)R b20 , N.R. c20 C(O)OR a20 , N.R. c20 C(O)NR c20 R d20 , C(=NR e20 )R b20 , C(=NOR a20 )R b20 , C(=NR e20 )NR c20 R d20 , N.R. c20 C(=NR e20 )NR c20 R d20 , N.R. c20 S(O)R b20 , N.R. c20 S(O) 2 R b20 , N.R. c20 S(O) 2 NR c20 R d20 , S(O)Rb20 , S(O)NR c20 R d20 , S(O) 2 R b20 , S(O) 2 NR c20 R d20 , and B.R. h20 R i20 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 21 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 21 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a21 , S.R. a21 , C(O)R b21 , C(O)NR c21 R d21 , C(O)OR a21 , O.C.(O)R b21 , O-C(O)NR c21 Rd21 , N.R. c21 R d21 , N.R. c21 C(O)R b21 , N.R. c21 C(O)OR a21 , N.R. c21 C(O)NR c21 R d21 , N.R. c21 S(O)R b21 , N.R. c21 S(O) 2 R b21 , N.R. c21 S(O) 2 NR c21 R d21 , S(O)R b21 , S(O)NR c21 R d21 , S(O) 2 R b21 , S(O) 2 NR c21 R d21 , and B.R. h21 R i21 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 22 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 22 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa22 , S.R. a22 , C(O)R b22 , C(O)NR c22 R d22 , C(O)OR a22 , O.C.(O)R b22 , O-C(O)NR c22 R d22 , N.R. c22 R d22 , N.R. c22 C(O)R b22 , N.R. c22 C(O)OR a22 , N.R. c22 C(O)NR c22 R d22 , N.R. c22 S(O)R b22 , N.R. c22 S(O) 2 R b22 , N.R. c22 S(O) 2 NR c22 R d22 , S(O)R b22 , S(O)NR c22 R d22 , S(O) 2 R b22 , S(O) 2 NR c22 R d22 , and B.R. h22 R i22 are independently selected from; Each R 23 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a23 , S.R.a23 , C(O)R b23 , C(O)NR c23 R d23 , C(O)OR a23 , O.C.(O)R b23 , O-C(O)NR c23 R d23 , N.R. c23 R d23 , N.R. c23 C(O)R b23 , N.R. c23 C(O)OR a23 , N.R. c23 C(O)NR c23 R d23 , N.R. c23 S(O)R b23 , N.R. c23 S(O) 2 R b23 , N.R. c23 S(O) 2 NR c23 R d23 , S(O)R b23 , S(O)NR c23 R d23 , S(O) 2 R b23 , S(O) 2 NR c23 R d23 , and B.R. h23 R i23 are independently selected from; Each R 30 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a30 , S.R. a30 , C(O)Rb30 , C(O)NR c30 R d30 , C(O)OR a30 , O.C.(O)R b30 , O-C(O)NR c30 R d30 , N.R. c30 R d30 , N.R. c30 C(O)R b30 , N.R. c30 C(O)OR a30 , N.R. c30 C(O)NR c30 R d30 , N.R. c30 S(O)R b30 , N.R. c30 S(O) 2 R b30 , N.R. c30 S(O) 2 NR c30 R d30 , S(O)R b30 , S(O)NR c30 R d30 , S(O) 2 R b30 , S(O) 2 NR c30 R d30 , and B.R. h30 R i30 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 31 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a31 , S.R. a31 , C(O)R b31 , C(O)NR c31 R d31 , C(O)OR a31 , O.C.(O)R b31 , O-C(O)NR c31 R d31 , N.R. c31 R d31 , N.R. c31 C(O)R b31 , N.R. c31 C(O)OR a31 , N.R. c31 C(O)NR c31 R d31 , N.R. c31 S(O)R b31 , N.R. c31 S(O) 2 R b31 , N.R. c31 S(O) 2 NR c31 R d31 , S(O)R b31 , S(O)NR c31 R d31 , S(O) 2 R b31 , S(O) 2 NR c31 R d31 , and B.R. h31 R i31 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 32 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 32 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a32 , S.R. a32 , C(O)R b32 , C(O)NR c32 R d32 , C(O)OR a32 , O.C.(O)R b32 , O-C(O)NR c32 R d32 , N.R. c32 R d32 , N.R. c32 C(O)R b32 , N.R. c32 C(O)OR a32 , N.R. c32 C(O)NR c32 R d32 , N.R. c32 S(O)R b32 , N.R. c32 S(O) 2 R b32 , N.R. c32 S(O) 2 NR c32 R d32 , S(O)R b32 , S(O)NR c32 R d32 , S(O) 2 R b32 , S(O) 2 NR c32 R d32, and B.R. h32 R i32 are independently selected from; Each R 60 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a60 , S.R. a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , O.C.(O)R b60 , O-C(O)NR c60 R d60 , N.R. c60 R d60 , N.R. c60 C(O)R b60 , N.R. c60 C(O)OR a60 , N.R. c60 C(O)NR c60 R d60 , N.R. c60 S(O)R b60 , N.R. c60 S(O) 2 R b60 , N.R. c60 S(O) 2 NR c60 R d60 , S(O)R b60 , S(O)NR c60 R d60 , S(O) 2 R b60 , S(O) 2 NR c60 R d60 , and B.R. h60R i60 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 61 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 61 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a61 , S.R. a61 , C(O)R b61 , C(O)NR c61 R d61 , C(O)OR a61 , O.C.(O)R b61 , O-C(O)NR c61 R d61 , N.R. c61 R d61 , N.R. c61 C(O)R b61 , N.R. c61 C(O)OR a61 , N.R. c61 C(O)NRc61 R d61 , N.R. c61 S(O)R b61 , N.R. c61 S(O) 2 R b61 , N.R. c61 S(O) 2 NR c61 R d61 , S(O)R b61 , S(O)NR c61 R d61 , S(O) 2 R b61 , S(O) 2 NR c61 R d61 , and B.R. h61 R i61 are independently selected from; Each R 70 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, NO 2 , OR a70 , S.R. a70 , C(O)R b70 , C(O)NR c70 R d70 , C(O)OR a70 , O.C.(O)R b70 , O-C(O)NR c70 R d70 , N.R. c70 R d70 , N.R. c70 C(O)R b70 , N.R. c70 C(O)OR a70 , N.R. c70 C(O)NR c70 Rd70 , N.R. c70 S(O)R b70 , N.R. c70 S(O) 2 R b70 , N.R. c70 S(O) 2 NR c70 R d70 , S(O)R b70 , S(O)NR c70 R d70 , S(O) 2 R b70 , S(O) 2 NR c70 R d70 , and B.R. h70 R i70 are independently selected from; R a1 , R b1 , R c1 , and R d1 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R g or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c1 and R d1 together with the N atom to which they are attached, R g forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h1 and R i1 are OH and C, respectively. 1~6Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h1 and R i1 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a2 , R b2 , R c2 , and R d2 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 23 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c2 and R d2 together with the N atom to which they are attached, R 23 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e2 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h2 and R i2 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h2 and R i2 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a3 , R b3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 30 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c3 and R d3 together with the N atom to which they are attached, R 30forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e3 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h3 and R i3 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h3 and R i3 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a5 , R b5 , R c5 , and R d5 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R g or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c5 and R d5 together with the N atom to which they are attached, R g forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R e5 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h5 and R i5 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h5 and R i5 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a6 , R b6 , R c6 , and Rd6 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 60 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c6 and R d6 together with the N atom to which they are attached, R 60 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R e6 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h6 and R i6 are OH and C, respectively. 1~6 Alkoxy and C 1~6haloalkoxy, or any R bonded to the same B atom h6 and R i6 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a7 , R b7 , R c7 , and R d7 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 70 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c7 and R d7 together with the N atom to which they are attached, R 70 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e7 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h7 and R i7 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h7 and R i7 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a10 , R b10 , R c10 , and R d10 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 11 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c10 and R d10 together with the N atom to which they are attached, R 11forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e10 H, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h10 and R i10 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h10 and R i10 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a11 , R b11 , R c11 , and R d11 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom c11 and R d11together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R h11 and R i11 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h11 and R i11 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a20 , R b20 , R c20 , and R d20 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 21 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c20 and R d20 together with the N atom to which they are attached, R 21 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R e20 H, CN, C 1~6 Alkyl, C2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkylthio, C 1~6 Alkylsulfonyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylaminosulfonyl, Carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl)carbamyl, aminosulfonyl, C 1~6 Alkylaminosulfonyl, and di(C 1~6 alkyl)aminosulfonyl; R h20 and R i20 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h20 and R i20 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a21 , R b21 , R c21 , and R d21 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R 22 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c21 and R d21 together with the N atom to which they are attached, R 22 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h21 and R i21 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h21 and R i21 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a22 , R b22 , R c22 , and R d22 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 independently selected from haloalkyl; R h22 and R i22 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h22 and R i22 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a23 , R b23 , R c23 , and R d23 are H and C, respectively. 1~6 Alkyl, C2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom c23 and R d23 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R h23 and R i23 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h23 and R i23 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a30 , R b30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 31 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c30 and R d30 together with the N atom to which they are attached, R 31 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R h30 and R i30 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h30 and R i30 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a31 , R b31 , R c31 , and R d31 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R 32 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c31 and R d31 together with the N atom to which they are attached, R 32forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R h31 and R i31 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h31 and R i31 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a32 , R b32 , R c32 , and R d32 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 independently selected from haloalkyl; Alternatively, any R bonded to the same N atom c32 and R d32 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R h32 and R i32 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h32 and R i32 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a60 , R b60 , R c60 , and R d60are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 61 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c60 and R d60 together with the N atom to which they are attached, R 61 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R h60 and R i60 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h60 and R i60 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a61 , R b61 , R c61 , and R d61 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom c61 and R d61 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R h61 and R i61 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h61 and R i61 together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R a70 , R b70 , R c70 , and R d70 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom c70 and R d70 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R h70 and R i70 are OH and C, respectively. 1~6 Alkoxy and C 1~6 haloalkoxy, or any R bonded to the same B atom h70 and R i70together with the B atoms to which they are attached, 1~6 Alkyl and C 1~6 forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; Each R g D, OH, NO 2 ,CN,Haro,C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, C 3~6 Cycloalkyl-C 1~2 Alkylene, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 1~3 Alkoxy-C 1~3 Alkyl, C 1~3 Alkoxy-C 1~3 Alkoxy, HO-C 1~3 Alkoxy, HO-C 1~3 Alkyl, Cyano-C 1~3 Alkyl, H 2 NC 1~3 Alkyl, Amino, C 1~6 Alkylamino, di(C 1~6 Alkyl)amino, thio, C 1~6 Alkylthio, C 1~6 Alkylsulfinyl, C 1~6 Alkyl sulfonyl, carbamyl, C 1~6 Alkylcarbamyl, di(C 1~6 Alkyl) carbamyl, carboxy, C 1~6 Alkyl carbonyl, C 1~6 Alkoxycarbonyl, C 1~6 Alkylcarbonylamino, C 1~6 Alkoxycarbonylamino, C 1~6 Alkylcarbonyloxy, aminocarbonyloxy, C 1~6 Alkylaminocarbonyloxy, di(C 1~6 Alkyl)aminocarbonyloxy, C 1~6 Alkyl sulfonylamino, aminosulfonyl, C 1~6Alkylaminosulfonyl, di(C 1~6 Alkyl)aminosulfonyl, aminosulfonylamino, C 1~6 Alkylaminosulfonylamino, di(C 1~6 Alkyl)aminosulfonylamino, aminocarbonylamino, C 1~6 Alkylaminocarbonylamino, and di(C 1~6 alkyl)aminocarbonylamino.

[0012] In another embodiment, the compound of formula I is a compound of formula II: [ka] or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 H, D, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , S.R. a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , O.C.(O)R b1 , O-C(O)NR c1 R d1 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)OR a1 , N.R. c1C(O)NR c1 R d1 , N.R. c1 S(O) 2 R b1 , N.R. c1 S(O) 2 NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 Selected from; R 2 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a2 , S.R. a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , O.C.(O)R b2 , O-C(O)NR c2 R d2 , N.R. c2 R d2 , N.R. c2 C(O)R b2 , N.R. c2 C(O)OR a2 , N.R. c2 C(O)NR c2 R d2 , N.R. c2 S(O) 2 R b2 , N.R. c2 S(O) 2 NR c2 R d2 , S(O)2 R b2 , and S(O) 2 NR c2 R d2 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 23 substituted with 1, 2, 3, or 4 substituents independently selected from Cy 1 is C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 6-10 membered heteroaryl and 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 substituted with 1, 2, 3, or 4 substituents independently selected from R 4 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a3 , S.R. a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , O.C.(O)R b3 , O-C(O)NR c3 R d3 , N.R. c3 R d3 , N.R. c3 C(O)R b3 , N.R. c3 C(O)OR a3 , N.R. c3 C(O)NR c3 R d3 , N.R. c3 S(O) 2 R b3 , N.R. c3 S(O) 2 NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R30 substituted with 1, 2, 3, or 4 substituents independently selected from R 5 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a5 , S.R. a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , O.C.(O)R b5 , O-C(O)NR c5 R d5 , N.R. c5 R d5 , N.R. c5 C(O)R b5 , N.R. c5 C(O)OR a5 , N.R. c5 C(O)NR c5 R d5 , N.R. c5 S(O) 2 R b5 , N.R. c5 S(O) 2 NR c5 R d5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 Selected from; R 6 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a6 , S.R. a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , O.C.(O)R b6 , O-C(O)NR c6 R d6 , N.R. c6 R d6 , N.R. c6 C(O)R b6 , N.R. c6 C(O)OR a6 , N.R. c6 C(O)NR c6 R d6 , N.R. c6 S(O) 2 R b6 , N.R. c6 S(O) 2 NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 C above is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 60 substituted with 1, 2, 3, or 4 substituents independently selected from R 7 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a7 , S.R. a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , O.C.(O)R b7 , O-C(O)NR c7 R d7 , N.R. c7 R d7 , N.R. c7 C(O)R b7 , N.R. c7 C(O)OR a7 , N.R. c7 C(O)NR c7 R d7 , N.R. c7 S(O) 2 R b7 , N.R. c7 S(O) 2 NR c7 R d7 , S(O) 2 R b7 , and S(O) 2 NR c7 R d7 Selected from; Cy 2 is C 3~10Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 20 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 10 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a10 , S.R. a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , O.C.(O)R b10 , O-C(O)NR c10 R d10 , N.R. c10 R d10 , N.R. c10 C(O)R b10 , N.R. c10 C(O)OR a10 , N.R. c10C(O)NR c10 R d10 , N.R. c10 S(O) 2 R b10 , N.R. c10 S(O) 2 NR c10 R d10 , S(O) 2 R b10 , and S(O) 2 NR c10 R d10 are independently selected from; Each R 20 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a20 , S.R. a20 , C(O)R b20 , C(O)NR c20 R d20 , C(O)OR a20 , O.C.(O)R b20 , O-C(O)NR c20 R d20 , N.R. c20 R d20 , N.R. c20 C(O)R b20 , N.R. c20 C(O)OR a20 , N.R. c20 C(O)NR c20 R d20 , N.R. c20 S(O) 2 R b20 , N.R. c20 S(O) 2 NR c20 R d20 , S(O)2 R b20 , S(O) 2 NR c20 R d20 Independently selected from the above C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 21 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 21 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a21 , S.R. a21 , C(O)R b21 , C(O)NR c21 R d21 , C(O)OR a21 , O.C.(O)R b21 , O-C(O)NR c21 R d21 , N.R. c21 R d21 , N.R. c21 C(O)R b21 , N.R.c21 C(O)OR a21 , N.R. c21 C(O)NR c21 R d21 , N.R. c21 S(O) 2 R b21 , N.R. c21 S(O) 2 NR c21 R d21 , S(O) 2 R b21 , and S(O) 2 NR c21 R d21 are independently selected from; Each R 23 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a23 , S.R. a23 , C(O)R b23 , C(O)NR c23 R d23 , C(O)OR a23 , O.C.(O)R b23 , O-C(O)NR c23 R d23 , N.R. c23 R d23 , N.R. c23 C(O)R b23 , N.R. c23 C(O)OR a23 , N.R. c23 C(O)NR c23 R d23 , N.R. c23 S(O) 2 R b23 , N.R. c23 S(O)2 NR c23 R d23 , S(O) 2 R b23 , and S(O) 2 NR c23 R d23 are independently selected from; Each R 30 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a30 , S.R. a30 , C(O)R b30 , C(O)NR c30 R d30 , C(O)OR a30 , O.C.(O)R b30 , O-C(O)NR c30 R d30 , N.R. c30 R d30 , N.R. c30 C(O)R b30 , N.R. c30 C(O)OR a30 , N.R. c30 C(O)NR c30 R d30 , N.R. c30 S(O) 2 R b30 , N.R. c30 S(O) 2 NR c30 R d30 , S(O) 2 R b30 , and S(O) 2 NR c30 R d30 Independently selected from the above C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene and 5-10 membered heteroaryl-C 1~3 Each alkylene is optionally represented by R 31 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a31 , S.R. a31 , C(O)R b31 , C(O)NR c31 R d31 , C(O)OR a31 , O.C.(O)R b31 , O-C(O)NR c31 R d31 , N.R. c31 R d31 , N.R. c31 C(O)R b31 , N.R. c31 C(O)OR a31 , N.R. c31 C(O)NR c31 R d31 , N.R. c31 S(O)2 R b31 , N.R. c31 S(O) 2 NR c31 R d31 , S(O) 2 R b31 , and S(O) 2 NR c31 R d31 are independently selected from; Each R 60 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, C 3~10 Cycloalkyl-C 1~3 Alkylene, 4-10 membered heterocycloalkyl-C 1~3 Alkylene, C 6~10 Aryl-C 1~3 Alkylene, 5-10 membered heteroaryl-C 1~3 Alkylene, Halo, D, CN, OR a60 , S.R. a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , O.C.(O)R b60 , O-C(O)NR c60 R d60 , N.R. c60 R d60 , N.R. c60 C(O)R b60 , N.R. c60 C(O)OR a60 , N.R. c60 C(O)NR c60 R d60 , N.R. c60 S(O) 2 R b60 , N.R. c60 S(O) 2 NR c60 R d60 , S(O) 2 R b60 , and S(O) 2 NRc60 R d60 are independently selected from; R a1 , R b1 , R c1 , and R d1 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom c1 and R d1 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R a2 , R b2 , R c2 , and R d2 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 23 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c2 and R d2 together with the N atom to which they are attached, R 23forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R a3 , R b3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 30 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c3 and R d3 together with the N atom to which they are attached, R 30 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R a5 , R b5 , R c5 , and R d5 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom c5 and R d5together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R a6 , R b6 , R c6 , and R d6 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 60 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c6 and R d6 together with the N atom to which they are attached, R 60 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R a7 , R b7 , R c7 , and R d7 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom c7 and R d7together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R a10 , R b10 , R c10 , and R d10 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom c10 and R d10 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R a20 , R b20 , R c20 , and R d20 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 21 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c20 and R d20 together with the N atom to which they are attached, R 21forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R a21 , R b21 , R c21 , and R d21 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom c21 and R d21 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R a23 , R b23 , R c23 , and R d23 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom c23 and R d23 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R a30 , R b30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10aryl, and 5-10 membered heteroaryl, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 5-10 membered heteroaryl are each optionally represented by R 31 or substituted with 1, 2, 3, or 4 substituents independently selected from; Alternatively, any R bonded to the same N atom c30 and R d30 together with the N atom to which they are attached, R 31 forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R a31 , R b31 , R c31 , and R d31 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~6 independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom c31 and R d31 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R a60 , R b60 , R c60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 5-10 membered heteroaryl; and Alternatively, any R bonded to the same N atom c60 and R d60 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group.

[0013] In another embodiment of Formula II or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 is H; R 2 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, CN, OR a2 , and N.R. c2 R d2 C above is selected from 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from Cy 1 is C 6~10 aryl, and 6-10 membered heteroaryl, the 6-10 membered heteroaryl having at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, the ring-forming carbon atoms of the 6-10 membered heteroaryl being optionally substituted by oxo to form a carbonyl group; C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 substituted with 1, 2, or 3 substituents independently selected from R 4 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10Cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, CN, OR a3 , C(O)NR c3 R d3 , and N.R. c3 R d3 C above is selected from 1~6 Alkyl, C 3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 substituted with 1 or 2 substituents independently selected from R 5 is H; R 6 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, halo, CN, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, OR a6 , and N.R. c6 R d6 C above is selected from 1~6 Each of the alkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R 7 is a halo; Cy 2 is a 4- to 7-membered heterocycloalkyl having at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, a ring-forming carbon atom of the 4- to 7-membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group, and the 4- to 7-membered heterocycloalkyl is optionally substituted by R 20 substituted with 1 or 2 substituents independently selected from Each R 10 is C 1~6 Alkyl, C 1~6 independently selected from haloalkyl, halo, CN, and OH; Each R 20 is C 1~6 Alkyl, C 1~6Haloalkyl, Halo, CN, OR a20 , C(O)R b20 , C(O)NR c20 R d20 , and N.R. c20 R d20 are independently selected from; Each R 23 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, CN, OR a23 , and N.R. c23 R d23 are independently selected from; Each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, CN, OR a30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 substituted with 1 or 2 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, CN, OR a31 , and N.R. c31 R d31 are independently selected from; Each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, CN, OR a60 , C(O)NR c60 R d60 , C(O)OR a60 , and N.R. c60 R d60 are independently selected from; R a2 , R c2 , and R d2 are H and C, respectively. 1~6 Alkyl, and C1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from R a3 , R b3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl; 1~6 Alkyl, C 3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 substituted with 1 or 2 substituents independently selected from R a6 , R c6 , and R d6 are H and C, respectively. 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R a20 , R b20 , R c20 , and R d20 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R 21 substituted with 1, 2, or 3 substituents independently selected from R a23 , R c23 , and R d23 are H and C, respectively. 1~6 Alkyl, and C 1~6independently selected from haloalkyl; R a30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 substituted with 1 or 2 substituents independently selected from R a31 , R c31 , and R d31 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a60 , R c60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, and 4 to 10 membered heterocycloalkyl.

[0014] In yet another embodiment of Formula II or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 H, D, C 1~6 Alkyl, and C 1~6 haloalkyl; R 2 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a2 , and N.R.c2 R d2 C above is selected from 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from Cy 1 is C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; the ring-forming carbon atoms of the 6-10 membered heteroaryl and the 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 substituted with 1, 2, or 3 substituents independently selected from R 4 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, D, CN, OR a3 , C(O)NR c3 R d3 , and N.R. c3 R d3 C above is selected from 1~6 Alkyl, C 3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 substituted with 1 or 2 substituents independently selected from R 5 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a5 , and N.R. c5 R d5 Selected from; R 6 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a6 , and N.R. c6 R d6 C above is selected from 1~6 Alkyl is optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R 7 , H, C 1~6 Alkyl, and C 1~6 Haloalkyl, Halo, D, CN, OR a7 , and N.R. c7 R d7 Selected from; Cy 2 is selected from 4- to 7-membered heterocycloalkyl having at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, a ring-forming carbon atom of the 4- to 7-membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group, and the 4- to 7-membered heterocycloalkyl is optionally selected from R 20 substituted with 1 or 2 substituents independently selected from Each R 10 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a10 , C(O)NR c10 R d10 , and N.R. c10 R d10 are independently selected from; Each R 20 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a20 , C(O)R b20 , C(O)NR c20 R d20 , and N.R. c20 R d20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 substituted with 1 or 2 substituents independently selected from Each R 21 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a21 , and N.R. c21 R d21 are independently selected from; Each R 23 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a23 , and N.R. c23 R d23 are independently selected from; Each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 substituted with 1 or 2 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a31 , and N.R. c31 R d31 are independently selected from; Each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)NR c60 R d60 , C(O)OR a60 , and N.R. c60 R d60 are independently selected from; R a2 , R c2 , and R d2 are H and C, respectively.1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from R a3 , R b3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl; 1~6 Alkyl, C 3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom c3 and R d3 together with the N atom to which they are attached, R 30 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R a5 , R c5 , and R d5 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a6 , R c6 , and R d6 are H and C, respectively. 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R a7 , R c7 , and R d7 are H and C, respectively. 1~6 Alkyl, and C1~6 independently selected from haloalkyl; R a10 , R b10 , R c10 , and R d10 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a20 , R b20 , R c20 , and R d20 are H and C, respectively. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R 21 substituted with 1, 2, or 3 substituents independently selected from R a21 , R c21 , and R d21 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a23 , R c23 , and R d23 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atomc30 and R d30 together with the N atom to which they are attached, R 31 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R a31 , R c31 , and R d31 are H and C, respectively. 1~6 Alkyl, C 1~6 independently selected from haloalkyl; R a60 , R c60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, and 4 to 10 membered heterocycloalkyl; and Alternatively, any R bonded to the same N atom c60 and R d60 together with the N atom to which they are attached form a 4-, 5-, or 6-membered heterocycloalkyl group.

[0015] In yet another embodiment of Formula II or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 is H; R 2 , H, C 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from Cy 1 is C 3~10Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 substituted with 1 or 2 substituents independently selected from R 4 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, CN, OR a3 , and N.R. c3 R d3 C above is selected from 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 30 substituted with 1 or 2 substituents independently selected from R 5 , H, C 1~6 Alkyl, and C 1~6 haloalkyl; R 6 , H, C 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R 7 , H, C 1~6 Alkyl, and C 1~6 selected from haloalkyl, halo, D, and CN; Cy 2 is selected from 4- to 6-membered heterocycloalkyl having at least one ring-forming carbon atom and 1 or 2 ring-forming heteroatoms independently selected from N and O, and the 4- to 6-membered heterocycloalkyl is optionally selected from R20 substituted with 1 or 2 substituents independently selected from Each R 10 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, and OR a10 are independently selected from; Each R 20 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, and C(O)R b20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 substituted with 1 or 2 substituents independently selected from Each R 21 is C 1~6 Alkyl, C 1~6 independently selected from haloalkyl, halo, D, and CN; Each R 23 is C 1~6 Alkyl, C 1~6 independently selected from haloalkyl, halo, D, and CN; Each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 substituted with 1 or 2 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 1~6 independently selected from haloalkyl, halo, D, and CN; Each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)NR c60 R d60 , C(O)OR a60, and N.R. c60 R d60 are independently selected from; R a3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 1~6 haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 30 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom c3 and R d3 together with the N atom to which they are attached, R 30 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: Each R a10 , H, C 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; Each R b20 is C 2~6 Alkenyl, and C 2~6 alkynyl, 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R 21 substituted with 1, 2, or 3 substituents independently selected from R a30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 1~6 haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom c30 and R d30together with the N atom to which they are attached, R 31 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R a60 , R c60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 1~6 independently selected from haloalkyl, and 4 to 10 membered heterocycloalkyl; and Alternatively, any R bonded to the same N atom c60 and R d60 together with the N atom to which they are attached form a 4-, 5-, or 6-membered heterocycloalkyl group.

[0016] In another embodiment of Formula II or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 is H; R 2 is R 23 C optionally substituted with 1, 2, 3, or 4 substituents independently selected from 1~6 is alkyl; Cy 1 is C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 6-10 membered heteroaryl and 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 substituted with 1, 2, 3, or 4 substituents independently selected from R 3 does not exist; R 4 is C 1~6 Alkyl, 4-10 membered heterocycloalkyl, and OR a3 C above is selected from 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 30 substituted with 1, 2, 3, or 4 substituents independently selected from R 5 is H; R 6 is R 60 C optionally substituted with 1, 2, 3, or 4 substituents independently selected from 1~6 is alkyl; R 7 , H, C 1~6 alkyl, and halo; Cy 2 is R 20 is a 4-14 membered heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R 10 is C 1~6 Alkyl, halo, CN, and OR a10 are independently selected from; Each R 20 is C 1~6 Alkyl, and C(O)Rb20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 21 is independently selected from halo and CN; Each R 23 is CN; Each R 30 is 4-10 membered heterocycloalkyl, and NR c30 R d30 wherein the 4-10 membered heterocycloalkyl is optionally selected from R 31 substituted with 1, 2, 3, or 4 substituents independently selected from Each R 31 is C 1~6 independently selected from alkyl, alkyl, and halo; Each R 60 is a 4-10 membered heterocycloalkyl, C(O)NR c60 R d60 , and C(O)OR a60 are independently selected from; Each R a3 is R 30 C optionally substituted with 1, 2, 3, or 4 substituents independently selected from 1~6 is alkyl; Each R a10 is H; Each R b20 is R 21 C optionally substituted with 1, 2, 3, or 4 substituents independently selected from 2~6 alkenyl; R c30 and R d30 are R 31 C optionally substituted with 1, 2, 3, or 4 substituents independently selected from 1~6 is alkyl; R a60 , R c60 , and R d60 are respectively, C 1~6 It is an alkyl.

[0017] In another embodiment of Formula II or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N or CR 5 and; Y is N or CR 6 and; R 1 is H; R 2 is R 23 C optionally substituted with 1, 2, or 3 substituents independently selected from 1~6 is alkyl; Cy 1 is selected from naphthyl, benzothiazolyl, chromyl, phenyl, indolyl, indolinyl, tetrahydroquinolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally coupled with R 10 substituted with 1, 2, or 3 substituents independently selected from R 4 is C 1~6 alkyl, 4-10 membered heterocycloalkyl, 6-10 membered heteroaryl, and OR a3 C above is selected from 1~6 Alkyl, 4- to 10-membered heterocycloalkyl, and 6- to 10-membered heteroaryl are each optionally represented by R 30 substituted with 1, 2, or 3 substituents independently selected from R 5 is H; R 6 is C 1~6 alkyl, 4-10 membered heterocycloalkyl, dihydroindolizinonyl; 1~6 Alkyl and 4-10 membered heterocycloalkyl are optionally represented by R 60 substituted with 1, 2, or 3 substituents independently selected from R 7 is C 1~3 is alkyl or halo; Cy2 is R 20 is a 4-14 membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from Each R 10 is C 1~6 independently selected from alkyl, halo, CN, and OH; Each R 20 is C 1~6 Alkyl, and C(O)R b20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 substituted with 1, 2, or 3 substituents independently selected from Each R 21 is independently selected from halo and CN; Each R 23 is CN; Each R 30 is C 1~6 Alkyl, 4-10 membered heterocycloalkyl, C(O)NR c30 R d30 , and N.R. c30 R d30 wherein the 4-10 membered heterocycloalkyl is optionally selected from R 31 substituted with 1, 2, or 3 substituents independently selected from Each R 31 is C 1~6 independently selected from alkyl, alkyl, and halo; Each R 60 is 4-10 membered heterocycloalkyl, pyridinonyl, C(O)NR c60 R d60 , C(O)R a60 , and C(O)OR a60 are independently selected from; Each R a3 is R 30 C optionally substituted with 1, 2, or 3 substituents independently selected from 1~6 is alkyl; Each R b20 is R 21 C optionally substituted with 1, 2, or 3 substituents independently selected from 2~6alkenyl; R c30 and R d30 are each independently H or C 1~6 is alkyl; R a60 , R c60 , and R d60 are each independently H or C 1~6 It is an alkyl.

[0018] In another embodiment of Formula I or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 H, D, C 1~6 Alkyl, and C 1~6 haloalkyl; R 2 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a2 , and N.R. c2 R d2 C above is selected from 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from Cy 1 is C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; the ring-forming carbon atoms of the 6-10 membered heteroaryl and the 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 substituted with 1, 2, or 3 substituents independently selected from R 4 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, D, CN, OR a3 , C(O)NR c3 R d3 , and N.R. c3 R d3 C above is selected from 1~6 Alkyl, C 3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 substituted with 1 or 2 substituents independently selected from R 5 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a5 , and N.R. c5 R d5 Selected from; R 6 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a6 , and N.R. c6 R d6 C above is selected from 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R 7 , H, C 1~6 Alkyl, and C 1~6 Haloalkyl, Halo, D, CN, OR a7 , and N.R. c7 R d7 Selected from; Cy2 is selected from 4- to 7-membered heterocycloalkyl having at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, a ring-forming carbon atom of the 4- to 7-membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group, and the 4- to 7-membered heterocycloalkyl is optionally selected from R 20 substituted with 1 or 2 substituents independently selected from Each R 10 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a10 , C(O)NR c10 R d10 , and N.R. c10 R d10 are independently selected from; Each R 20 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a20 , C(O)R b20 , C(O)NR c20 R d20 , and N.R. c20 R d20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 substituted with 1 or 2 substituents independently selected from Each R 21 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a21 , and N.R. c21 R d21 are independently selected from; Each R 23 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a23 , and N.R. c23 R d23 are independently selected from; Each R 30 is C 1~6 Alkyl, C 1~6Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , C(O)NR c30 R d30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 substituted with 1 or 2 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a31 , and N.R. c31 R d31 are independently selected from; Each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , and N.R. c60 R d60 are independently selected from; R a2 , R c2 , and R d2 are H and C, respectively. 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from R a3 , R b3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl; 1~6 Alkyl, C 3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom c3 and R d3 together with the N atom to which they are attached, R 30 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R a5 , R c5 , and R d5 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a6 , R c6 , and R d6 are H and C, respectively. 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R a7 , R c7 , and R d7 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a10 , R b10 , R c10 , and R d10 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a20 , R b20 , R c20 , and R d20 are H and C, respectively. 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 haloalkyl; 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R 21 substituted with 1, 2, or 3 substituents independently selected from R a21 , R c21 , and R d21 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a23 , R c23 , and R d23 are H and C, respectively. 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; R a30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom c30 and R d30 together with the N atom to which they are attached, R 31 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R a31 , R c31 , and R d31 are H and C, respectively. 1~6 Alkyl, C 1~6 independently selected from haloalkyl; Ra60 , R b60 , R c60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 cycloalkyl, and 4 to 10 membered heterocycloalkyl; and Alternatively, any R bonded to the same N atom c60 and R d60 together with the N atom to which they are attached form a 4-, 5-, or 6-membered heterocycloalkyl group.

[0019] In yet another embodiment of Formula I or a pharma- ceutically acceptable salt thereof, -AR 1 =BR 2 - is -N=CR 2 -and-CR 1 =N-selected; X is N and CR 5 Selected from; Y is N and CR 6 Selected from; R 1 is H; R 2 , H, C 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 23 substituted with 1 or 2 substituents independently selected from Cy 1 is C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R10 substituted with 1 or 2 substituents independently selected from R 4 , H, C 1~6 Alkyl, C 1~6 haloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, CN, OR a3 , and N.R. c3 R d3 C above is selected from 1~6 Each of the alkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally represented by R 30 substituted with 1 or 2 substituents independently selected from R 5 , H, C 1~6 Alkyl, and C 1~6 haloalkyl; R 6 , H, C 1~6 Alkyl, C 1~6 haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Alkyl and 4-10 membered heterocycloalkyl are optionally represented by R 60 substituted with 1 or 2 substituents independently selected from R 7 , H, C 1~6 Alkyl, and C 1~6 selected from haloalkyl, halo, D, and CN; Cy 2 is selected from 4- to 6-membered heterocycloalkyl having at least one ring-forming carbon atom and 1 or 2 ring-forming heteroatoms independently selected from N and O, and the 4- to 6-membered heterocycloalkyl is optionally selected from R 20 substituted with 1 or 2 substituents independently selected from Each R 10 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, and OR a10 are independently selected from; Each R 20 is C 1~6 Alkyl, C1~6 Haloalkyl, Halo, D, CN, and C(O)R b20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 substituted with 1 or 2 substituents independently selected from Each R 21 is C 1~6 Alkyl, C 1~6 independently selected from haloalkyl, halo, D, and CN; Each R 23 is C 1~6 Alkyl, C 1~6 independently selected from haloalkyl, halo, D, and CN; Each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , C(O)NR c30 R d30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 substituted with 1 or 2 substituents independently selected from Each R 31 is C 1~6 Alkyl, C 1~6 independently selected from haloalkyl, halo, D, and CN; Each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , and N.R. c60 R d60 are independently selected from; R a3 , R c3 , and R d3 are H and C, respectively. 1~6 Alkyl, C 1~6haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 30 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom c3 and R d3 together with the N atom to which they are attached, R 30 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: Each R a10 , H, C 1~6 Alkyl, and C 1~6 independently selected from haloalkyl; Each R b20 is C 2~6 Alkenyl, and C 2~6 alkynyl, 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R 21 substituted with 1, 2, or 3 substituents independently selected from R a30 , R c30 , and R d30 are H and C, respectively. 1~6 Alkyl, C 1~6 haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 or is substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom c30 and R d30 together with the N atom to which they are attached, R 31 forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R a60 , R b60 , Rc60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 1~6 independently selected from haloalkyl, and 4 to 10 membered heterocycloalkyl; and Alternatively, any R bonded to the same N atom c60 and R d60 together with the N atom to which they are attached form a 4-, 5-, or 6-membered heterocycloalkyl group.

[0020] In one embodiment, the compound of formula I is a compound of formula III: [ka] or a pharma- ceutically acceptable salt thereof.

[0021] In one embodiment of Formula III or a pharma- ceutically acceptable salt thereof, Cy 1 is selected from naphthyl, indolyl, tetrahydroquinolinyl, indolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally selected from OH, halo, CN, and C. 1~6 substituted with 1 or 2 substituents independently selected from alkyl; R 6 is oxazolidin-2-one, CO 2 C 1~6 Alkyl, and CON(C 1~6 Alkyl) 2 C optionally substituted with 1 or 2 substituents independently selected from 1~6 is alkyl; R 7 is selected from H and halo; Cy 2 is selected from 2-azabicyclo[2.1.1]hexane, and piperidine, both of which are optionally substituted with CO(C 2~6 haloalkenyl), and C 1~6 substituted with 1 or 2 substituents independently selected from alkyl-CN; R a3is optionally substituted with pyrrolidine or hexahydropyrrolidine; 1~6 alkyl, and the pyrrolidine is optionally C 1~6 The hexahydropyrrolidine is optionally substituted with halo.

[0022] In another embodiment of Formula III or a pharma- ceutically acceptable salt thereof, Cy 1 is selected from naphthyl, phenyl, benzothiazolyl, chromanyl, indolyl, tetrahydroquinolinyl, indolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally selected from OH, halo, CN, and C. 1~6 substituted with 1 or 2 substituents independently selected from alkyl; R 6 is C 1~6 alkyl, or dihydroindolizinone, wherein the alkyl is optionally selected from oxazolidin-2-one, pyridin-2-one, CO 2 C 1~6 Alkyl, COC 1~6 Alkyl, and CON(C 1~6 Alkyl) 2 substituted with 1 or 2 substituents independently selected from R 7 is selected from H and halo; Cy 2 is selected from 2-azabicyclo[2.1.1]hexane, and piperidine, both of which are optionally substituted with CO(C 2~6 haloalkenyl), and C 1~6 substituted with 1 or 2 substituents independently selected from alkyl-CN; R a3 is optionally substituted with pyrrolidine or hexahydropyrrolidine; 1~6 alkyl, and the pyrrolidine is optionally C 1~6 The hexahydropyrrolidine is optionally substituted with halo.

[0023] In another embodiment, the compound of formula I is a compound of formula IV: [ka] or a pharma- ceutically acceptable salt thereof.

[0024] In one embodiment of Formula IV or a pharma- ceutically acceptable salt thereof, Cy 1 is selected from naphthyl, indolyl, tetrahydroquinolinyl, indolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally selected from OH, halo, CN, and C. 1~6 substituted with 1 or 2 substituents independently selected from alkyl; R 6 is oxazolidin-2-one, CO 2 C 1~6 Alkyl, and CON(C 1~6 Alkyl) 2 C optionally substituted with 1 or 2 substituents independently selected from 1~6 is alkyl; R 7 is selected from H and halo; Cy 2 is selected from 2-azabicyclo[2.1.1]hexane, and piperidine, both of which are optionally substituted with CO(C 2~6 haloalkenyl), and C 1~6 substituted with 1 or 2 substituents independently selected from alkyl-CN; R a3 is optionally substituted with pyrrolidine, hexahydropyrrolidine; 1~6 alkyl, and the pyrrolidine is optionally C 1~6 The hexahydropyrrolidine is optionally substituted with halo.

[0025] In yet another embodiment, the compound of formula I is a compound of formula V: [ka] or a pharma- ceutically acceptable salt thereof.

[0026] In one embodiment of Formula V or a pharma- ceutically acceptable salt thereof, Cy 1 is selected from naphthyl, indolyl, tetrahydroquinolinyl, indolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally selected from OH, halo, CN, and C. 1~6 substituted with 1 or 2 substituents independently selected from alkyl; R 4 is N(C 1~6 Alkyl) 2 azetidine optionally substituted with 1 or 2 substituents independently selected from R 7 is selected from H and halo; Cy 2 is selected from 2-azabicyclo[2.1.1]hexane, and piperidine, both of which are optionally substituted with CO(C 2~6 haloalkenyl), and C 1~6 Substituted with 1 or 2 substituents independently selected from alkyl-CN.

[0027] In yet another embodiment, the compound of formula I is a compound of formula VI: [ka] or a pharma- ceutically acceptable salt thereof.

[0028] In one embodiment of Formula VI or a pharma- ceutically acceptable salt thereof, Cy 1 is selected from naphthyl, indolyl, tetrahydroquinolinyl, indolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally selected from OH, halo, CN, and C. 1~6 substituted with 1 or 2 substituents independently selected from alkyl; R 4 is N(C 1~6 Alkyl) 2azetidine optionally substituted with 1 or 2 substituents independently selected from R 6 is oxazolidin-2-one, CO 2 C 1~6 Alkyl, and CON(C 1~6 Alkyl) 2 C optionally substituted with 1 or 2 substituents independently selected from 1~6 is alkyl; R 7 is selected from H and halo; Cy 2 is selected from 2-azabicyclo[2.1.1]hexane, and piperidine, both of which are optionally substituted with CO(C 2~6 haloalkenyl), and C 1~6 Substituted with 1 or 2 substituents independently selected from alkyl-CN.

[0029] In another embodiment, the compound of formula I is a compound of formula VII: [ka] or a pharma- ceutically acceptable salt thereof.

[0030] In one embodiment of Formula VI or a pharma- ceutically acceptable salt thereof, R 2 is C 1~6 is alkyl; Cy 1 is selected from naphthyl, indolyl, tetrahydroquinolinyl, indolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally selected from OH, halo, CN, and C. 1~6 substituted with 1 or 2 substituents independently selected from alkyl; R 4 is N(C 1~6 Alkyl) 2 azetidine optionally substituted with 1 or 2 substituents independently selected from R 6 is oxazolidin-2-one, CO 2 C1~6 Alkyl, and CON(C 1~6 Alkyl) 2 C optionally substituted with 1 or 2 substituents independently selected from 1~6 is alkyl; R 7 H, halo, and C 1~6 alkyl; Cy 2 is selected from 2-azabicyclo[2.1.1]hexane, and piperidine, both of which are optionally substituted with CO(C 2~6 haloalkenyl), and C 1~6 Substituted with 1 or 2 substituents independently selected from alkyl-CN.

[0031] In yet another embodiment, (a) Cy 1 is other than 3,5-dimethylisoxazol-4-yl; (b)R 3 is CH 2 CF 3 It is unexpected.

[0032] In yet another embodiment, [ka] represents a double bond. In another embodiment, [ka] represents a single bond.

[0033] In one embodiment, -AR 1 =BR 2 - is -N=CR 2 In another embodiment, -AR 1 =BR 2 -CR 1 =N-.

[0034] In yet another embodiment, X is CR 5 and Y is CR 6In yet another embodiment, X is N and Y is CR 6 In one embodiment, X is N and Y is N. In another embodiment, X is CR 5 In yet another embodiment, X is N. In one embodiment, Y is CR 6 In another embodiment, Y is N.

[0035] In one embodiment, R 1 H, D, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , S.R. a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , O.C.(O)R b1 , O-C(O)NR c1 R d1 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)OR a1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 S(O) 2 R b1 , N.R. c1 S(O) 2 NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 In one embodiment, R 1 H, D, C 1~6 Alkyl, and C 1~6 In another embodiment, R 1 is H.

[0036] In one embodiment, R 2 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a2 , and N.R. c2 R d2 C above is selected from 1~6 Alkyl is optionally represented by R 23 In one embodiment, R 2 , H, C 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 23 In yet another embodiment, R 2 , H, C 1~6 Alkyl, and C 1~6 In yet another embodiment, R 2 is C optionally replaced by CN 1~6 It is an alkyl.

[0037] In one embodiment, Cy 1 is C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 6-10 membered heteroaryl and 4-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 is substituted with 1 or 2 substituents independently selected from

[0038] In another embodiment, Cy 1 is a 5-10 membered heterocycloalkyl, C 6~10 aryl, and 6-10 membered heteroaryl, each of which has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and N and S are optionally oxidized; ring-forming carbon atoms of the 6-10 membered heteroaryl and the 5-10 membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and 5-10 membered heterocycloalkyl, C 6~10 Aryl and 6-10 membered heteroaryl are each optionally represented by R 10 is substituted with 1 or 2 substituents independently selected from

[0039] In one embodiment, [ka] is a single bond, and R 4 is selected from =O and =S. In yet another embodiment, [ka] is a double bond, and R 3 does not exist.

[0040] In one embodiment, R 3 , H, C 1~6 Alkyl, C 3~10 cycloalkyl, and 4-10 membered heterocycloalkyl; 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 30 is substituted with 1 or 2 substituents independently selected from

[0041] In one embodiment, R 4 , H, C 1~6 Alkyl, C 1~6Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, D, CN, OR a3 , C(O)NR c3 R d3 , and N.R. c3 R d3 C above is selected from 1~6 Alkyl, C 3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 In one embodiment, R 4 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, CN, OR a3 , and N.R. c3 R d3 C above is selected from 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 30 In yet another embodiment, R 4 is C 1~6 Alkyl, 4-10 membered heterocycloalkyl, and OR a3 wherein the 4-10 membered heterocycloalkyl is optionally selected from R 30 is substituted with 1 or 2 substituents independently selected from

[0042] In one embodiment, R 4 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, D, CN, OR a3 , C(O)NR c3 R d3 , and N.R. c3 R d3 C above is selected from 1~6 Alkyl, C 3~10Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally represented by R 30 In one embodiment, R 4 , H, C 1~6 Alkyl, C 1~6 haloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, CN, OR a3 , and N.R. c3 R d3 C above is selected from 1~6 Each of the alkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally represented by R 30 In one embodiment, R 4 is C 1~6 alkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and OR a3 C above is selected from 1~6 Each of the alkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally represented by R 30 is substituted with 1 or 2 substituents independently selected from

[0043] In one embodiment, R 5 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a5 , and N.R. c5 R d5 In one embodiment, R 5 , H, C 1~6 Alkyl, and C 1~6 In one embodiment, R is selected from haloalkyl. 5 is H.

[0044] In one embodiment, R 6 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a6 , and N.R. c6 R d6C above is selected from 1~6 Alkyl is optionally represented by R 60 In one embodiment, R 6 , H, C 1~6 Alkyl, and C 1~6 haloalkyl; 1~6 Alkyl is optionally represented by R 60 In another embodiment, R 6 is R 60 C optionally substituted with 1 or 2 substituents independently selected from 1~6 It is an alkyl.

[0045] In one embodiment, R 6 , H, C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a6 , and N.R. c6 R d6 C above is selected from 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 60 In one embodiment, R 6 , H, C 1~6 Alkyl, C 1~6 haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Alkyl and 4-10 membered heterocycloalkyl are optionally represented by R 60 In one embodiment, R 6 is C 1~6 alkyl, and 4-10 membered heterocycloalkyl; 1~6 Alkyl and 4-10 membered heterocycloalkyl are optionally represented by R 60 is substituted with 1 or 2 substituents independently selected from

[0046] In one embodiment, R 7 , H, C1~6 Alkyl, and C 1~6 Haloalkyl, Halo, D, CN, OR a7 , and N.R. c7 R d7 In one embodiment, R 7 , H, C 1~6 Alkyl, and C 1~6 In yet another embodiment, R is selected from haloalkyl, halo, D, and CN. 7 , H, C 1~3 is selected from alkyl, and halo.

[0047] In one embodiment, Cy 2 is selected from 4 to 10 membered heterocycloalkyl, the 4 to 10 membered heterocycloalkyl optionally being selected from R 20 In one embodiment, Cy is substituted with 1, 2, or 3 substituents independently selected from 2 is selected from 4- to 7-membered heterocycloalkyl, the 4- to 7-membered heterocycloalkyl optionally being selected from R 20 In one embodiment, Cy is substituted with 1 or 2 substituents independently selected from 2 is selected from 4-6 membered heterocycloalkyl, the 4-6 membered heterocycloalkyl optionally being selected from R 20 In yet another embodiment, Cy is substituted with 1 or 2 substituents independently selected from 2 is R 20 is a 5-10 membered heterocycloalkyl optionally substituted with 1 or 2 substituents independently selected from:

[0048] In yet another embodiment, Cy 2 teeth, [ka] wherein n is 0, 1, or 2.

[0049] In one embodiment, Cy 2 Cy 2 In another embodiment, Cy 2 Cy2 In yet another embodiment, Cy 2 Cy 2 In yet another embodiment, Cy 2 Cy 2 In one embodiment, Cy 2 Cy 2 In one embodiment, Cy 2 Cy 2 -a and Cy 2 -e is selected.

[0050] In one embodiment, n is 0. In another embodiment, n is 1. In yet another embodiment, n is 2.

[0051] In one embodiment, Cy 2 Cy 2 -e and n is 0.

[0052] In one embodiment, each R 10 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a10 , C(O)NR c10 R d10 , and N.R. c10 R d10 In one embodiment, each R 10 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, and OR a10 In one embodiment, each R 10 is C 1~6 Independently selected from alkyl, halo, CN, and OH.

[0053] In one embodiment, each R 20 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a20 , C(O)R b20 , C(O)NR c20 R d20 , and N.R. c20 R d20Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 In one embodiment, each R 20 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, and C(O)R b20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 In one embodiment, each R 20 is C 1~6 Alkyl, and C(O)R b20 Independently selected from the above C 1~6 Alkyl is optionally represented by R 21 In another embodiment, each R 20 is C 1~6 Alkyl, and C(O)C 2~6 alkenyl, 1~6 Alkyl, and C 2~6 Each alkenyl is optionally substituted with 1 or 2 substituents independently selected from CN and halo.

[0054] In one embodiment, each R 21 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a21 , and N.R. c21 R d21 In one embodiment, each R 21 is C 1~6 Alkyl, C 1~6 In one embodiment, each R 21 is independently selected from halo and CN.

[0055] In one embodiment, each R 23 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a23 , and N.R.c23 R d23 In one embodiment, each R 23 is C 1~6 Alkyl, C 1~6 In one embodiment, each R 23 is CN.

[0056] In one embodiment, each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 In one embodiment, each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 In one embodiment, each R 30 is 4-10 membered heterocycloalkyl, and NR c30 R d30 wherein the 4-10 membered heterocycloalkyl is optionally selected from R 31 is substituted with 1 or 2 substituents independently selected from

[0057] In one embodiment, each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , C(O)NR c30 R d30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Alkyl, C 3~10 Cycloalkyl and 4-10 membered heterocycloalkyl are each optionally represented by R 31 In one embodiment, each R 30 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , C(O)NR c30 R d30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 In one embodiment, each R 30 is C 1~6 Alkyl, 4-10 membered heterocycloalkyl, C(O)NR c30 R d30 , and N.R. c30 R d30 Independently selected from the above C 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 is substituted with 1 or 2 substituents independently selected from

[0058] In one embodiment, each R 31 is C 1~6 Alkyl, C 1~6 Haloalkyl, Halo, D, CN, OR a31 , and N.R. c31 R d31 In one embodiment, each R 31 is C 1~6 Alkyl, C 1~6In another embodiment, each R 31 is C 1~6 is independently selected from alkyl, alkyl, and halo.

[0059] In one embodiment, each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)NR c60 R d60 , C(O)OR a60 , and N.R. c60 R d60 In another embodiment, each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)NR c60 R d60 , C(O)OR a60 , and N.R. c60 R d60 In yet another embodiment, each R 60 is a 4-10 membered heterocycloalkyl, C(O)NR c60 R d60 , and C(O)OR a60 In yet another embodiment, each R 60 is a 4-10 membered heterocycloalkyl, C(O)N(C 1~6 Alkyl) 2 , and C(O)OC 1~6 alkyl.

[0060] In one embodiment, each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)R b60 , C(O)NR c60 Rd60 , C(O)OR a60 , and N.R. c60 R d60 In one embodiment, each R 60 is C 1~6 Alkyl, C 1~6 Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , and N.R. c60 R d60 In one embodiment, each R 60 is 4-10 membered heterocycloalkyl, C(O)R b60 , C(O)NR c60 R d60 , and C(O)OR a60 are independently selected from

[0061] In one embodiment, each R a3 , H, C 1~6 Alkyl, C 1~6 haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 30 In yet another embodiment, each R a3 is R 30 C optionally substituted with 1 or 2 substituents independently selected from 1~6 alkyl, and each R 30 is C 1~6 and 4 to 10 membered heterocycloalkyl optionally substituted with 1 or 2 substituents independently selected from alkyl.

[0062] In one embodiment, each R a10 , H, C 1~6 Alkyl, and C 1~6 haloalkyl. In one embodiment, each R a10 is H.

[0063] In one embodiment, each R b20 is C 2~6 Alkenyl, and C 2~6 alkynyl, 2~6 Alkenyl, and C 2~6 Each alkynyl is optionally represented by R 21 In one embodiment, each R b20 is C 2~6 alkenyl, 2~6 Alkenyl is optionally represented by R 21 and wherein the aryl group is substituted with 1, 2, or 3 substituents independently selected from:

[0064] In one embodiment, R c30 and R d30 are H and C, respectively. 1~6 Alkyl, C 1~6 haloalkyl, and 4- to 10-membered heterocycloalkyl; 1~6 Each of alkyl and 4-10 membered heterocycloalkyl is optionally represented by R 31 In one embodiment, R c30 and R d30 are R 31 C optionally substituted with 1 or 2 substituents independently selected from 1~6 It is an alkyl.

[0065] In one embodiment, R c30 and R d30 are H and C, respectively. 1~6 alkyl, 1~6 Alkyl is optionally represented by R 31 is substituted with 1 or 2 substituents independently selected from

[0066] In one embodiment, R a60 , R c60 , and R d60 are H and C, respectively. 1~6 Alkyl, C 1~6In another embodiment, R a60 , R c60 , and R d60 is C 1~6 It is an alkyl.

[0067] In yet another embodiment, the compound of formula I is Methyl 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)propanoate; 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-4-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methoxy)-7-(3-hydroxynaphthalen-1-yl)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)methyl propanoate; 4-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-2-methyl-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-7-yl)naphthalen-2-ol; 4-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-2-methyl-4-((tetrahydro-1H-pyrrolidin-7a(5H)-yl)methoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-7-yl)naphthalen-2-ol; 3-((1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-methyl-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)methyl)oxazolidin-2-one; 3-((1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(5-fluoro-1H-indol-3-yl)-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)methyl)oxazolidin-2-one; 3-((1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(3,4-dihydroquinolin-1(2H)-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)methyl)oxazolidin-2-one; 1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(indolin-1-yl)-2-methyl-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridine; 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-imidazo[4,5-c][1,6]naphthyridin-2-yl)-N,N-dimethylpropanamide; 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(3-cyano-2,3-dihydro-1H-inden-4-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-1H-imidazo[4,5-c][1,6]naphthyridin-2-yl)-N,N-dimethylpropanamide; Methyl 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c][1,6]naphthyridin-2-yl)propanoate; 2-((2S,4S)-4-(4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-7-(5-fluoroquinolin-8-yl)-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-1-yl)-1-((E)-4-fluorobut-2-enoyl)piperidin-2-yl)acetonitrile; 2-((2S,4S)-4-(7-(5,6-dimethyl-1H-indazol-3-yl)-4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-1-yl)-1-(2-fluoroacryloyl)piperidin-2-yl)acetonitrile; 8-(1-((2S,4S)-2-(cyanomethyl)-1-(2-fluoroacryloyl)piperidin-4-yl)-4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-7-yl)-1-naphthonitrile; 8-(1-((2S,4S)-2-(cyanomethyl)-1-((E)-4-fluorobut-2-enoyl)piperidin-4-yl)-4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-7-yl)-1-naphthonitrile; 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-7-(3-hydroxynaphthalen-1-yl)-6,8-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl)-N,N-dimethylpropanamide; and 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-yl)-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl)-N,N-dimethylpropanamide; or a pharma- ceutically acceptable salt thereof is selected from.

[0068] In another embodiment, the compound of formula I is 4-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-2-methyl-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-7-yl)-6-fluoronaphthalen-2-ol; 1-((R)-2-(7-(benzo[d]thiazol-4-yl)-1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidin-1-yl)ethan-1-one; 3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)-2,3-dihydroindolizin-5(1H)-one; 1-((R)-1-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)ethyl)pyridin-2(1H)-one; (R)-2-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2,3-dichlorophenyl)-4-(3-(dimethylamino)-3-methylazetidin-1-yl)-6-fluoro-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate methyl; (R)-2-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2,3-dichlorophenyl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate methyl; and (R)-2-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2-chloro-3-methylphenyl)-6-fluoro-4-(6-(methylcarbamoyl)pyridin-2-yl)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate methyl; or a pharma- ceutically acceptable salt thereof is selected from.

[0069] In yet another embodiment, the compound of formula I is (R)-2-(7-(benzo[d]thiazol-4-yl)-1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-4-(((S)-1-(pyrrolidin-1-yl)propan-2-yl)oxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate methyl; (7aS)-5-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)tetrahydro-1H,3H-pyrrolo[1,2-c]oxazol-3-one; and 4-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)-N,N,1-trimethyl-1H-pyrazole-3-carboxamide; or a pharma- ceutically acceptable salt thereof is selected from.

[0070] In one embodiment, the compound of the formula herein is a compound of that formula or a pharma- ceutically acceptable salt thereof.

[0071] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of Formula I, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable carrier.

[0072] In one aspect, the description provides a method of inhibiting a KRAS protein having a G12C mutation, the method comprising contacting KRAS with a compound of the disclosure.

[0073] In another aspect, the present disclosure provides a method of inhibiting a KRAS protein having a G12D mutation, comprising contacting KRAS with a compound of the present disclosure.

[0074] In yet another aspect, the present disclosure provides a method of inhibiting a KRAS protein having a G12V mutation, the method comprising contacting KRAS with a compound of the present disclosure.

[0075] It is further recognized that certain features of the present disclosure that are described for clarity in the context of separate embodiments may also be provided in combination in a single embodiment (wherein the embodiments are intended to be combined as if described in a multiple dependent form). Conversely, various features of the present disclosure that are described for brevity in the context of a single embodiment may also be provided individually or in any suitable subcombination. Thus, it is contemplated that features described as embodiments of compounds of formula I may be combined in any suitable combination.

[0076] At various places in the present specification, certain features of compounds are disclosed in groups or ranges. It is specifically intended that such disclosures include any and all individual subcombinations of the members of such groups and ranges. For example, "C1~6 The term "alkyl" includes, but is not limited to, methyl, ethyl, C 3 Alkyl, C 4 Alkyl, C 5 Alkyl and C 6 It is specifically intended to disclose alkyl individually.

[0077] The term "n-membered", where n is an integer, typically refers to the number of ring-forming atoms in a moiety that has n ring-forming atoms. For example, piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5-membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group.

[0078] At various points in the specification, variable letters may be found that define divalent linking groups. Each linking substituent is specifically intended to include both the forward and reverse forms of the linking substituent. For example, -NR(CR'R'') n -NR(CR'R'') n -and-(CR'R'') n It is intended that both NR- and NR- are included and each form is disclosed individually.When a structure requires a linking group, it is understood that the Markush variable listed for that group is the linking group.For example, when a structure requires a linking group and the Markush group definition for that variable lists "alkyl" or "aryl", it is understood that "alkyl" or "aryl" represents a linking alkylene group or arylene group, respectively.

[0079] The term "substituted" means that an atom or group of atoms is formally replaced with hydrogen as a "substituent" attached to another group. The term "substituted" refers to any level of substitution, where such substitution is possible, for example, mono-, di-, tri-, tetra- or penta-substitution, unless otherwise indicated. Substituents are independently selected and may be at any chemically accessible position. It should be understood that substitution at a given atom is limited by valence. It should be understood that substitution at a given atom results in a chemically stable molecule. The phrase "optionally substituted" means unsubstituted or substituted. The term "substituted" means that a hydrogen atom has been removed and replaced by a substituent. A single divalent substituent, for example, oxo, can be replaced with two hydrogen atoms.

[0080] "C n~m " denotes an inclusive range, where n and m are integers and indicate the number of carbons. Examples include 1~4 , C 1~6 etc.

[0081] The term "alkyl", used alone or in combination with other terms, refers to a saturated hydrocarbon group which may be straight-chained or branched. n~m The term "alkyl" refers to an alkyl group having n to m carbon atoms. An alkyl group formally corresponds to an alkane with one C-H bond replaced at the point of attachment of the alkyl group to the remainder of the compound. In some embodiments, an alkyl group contains 1 to 6 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, or 1 to 2 carbon atoms. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl, and the like.

[0082] The term "alkenyl", used alone or in combination with other terms, refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more double carbon-carbon bonds. An alkenyl group formally corresponds to an alkene in which one C-H bond is replaced at the point of attachment of the alkenyl group to the remainder of the compound. n~m The term "alkenyl" refers to an alkenyl group having n to m carbons. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl, and the like.

[0083] The term "alkynyl," used alone or in combination with other terms, refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more triple carbon-carbon bonds. An alkynyl group formally corresponds to an alkyne in which one C-H bond is replaced at the point of attachment of the alkyl group to the remainder of the compound. n~m The term "alkynyl" refers to an alkynyl group having n to m carbons. Examples of alkynyl groups include, but are not limited to, ethynyl, propyn-1-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0084] The term "alkylene," used alone or in combination with other terms, refers to a divalent alkyl linking group. An alkylene group formally corresponds to an alkane with two C-H bonds replaced at the points of attachment of the alkylene group to the remainder of the compound. n~mThe term "alkylene" refers to an alkylene group having n to m carbon atoms. Examples of alkylene groups include, but are not limited to, ethane-1,2-diyl, ethane-1,1-diyl, propane-1,3-diyl, propane-1,2-diyl, propane-1,1-diyl, butane-1,4-diyl, butane-1,3-diyl, butane-1,2-diyl, 2-methyl-propane-1,3-diyl, and the like.

[0085] The term "alkoxy", used alone or in combination with other terms, refers to a radical of the formula -O-alkyl, where the alkyl group is as defined above. n~m The term "alkoxy" refers to an alkoxy group, the alkyl group of which has n to m carbons. Examples of alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy, and the like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. n~m The term "dialkoxy" refers to a group of the formula -O-(C n~m An example of a dialkyloxy group is -OCH 2 CH 2 O- and OCH 2 CH 2 CH 2 In some embodiments, C n~m Two O atoms of a dialkoxy group may be bonded to the same B atom to form a 5- or 6-membered heterocycloalkyl group.

[0086] The term "alkylthio", used alone or in combination with other terms, refers to a radical of the formula --S-alkyl, where the alkyl radical is as defined above.

[0087] The term "amino", used alone or in combination with other terms, has the formula -NH 2where the hydrogen atoms may be replaced with substituents described herein. For example, "alkylamino" refers to -NH(alkyl) and -N(alkyl) groups. 2 It may also refer to.

[0088] The term "carbonyl", used alone or in combination with other terms, refers to a -C(=O)- group, which can also be written as C(O).

[0089] The term "cyano" or "nitrile" refers to a group of formula -C≡N, which can also be written as -CN.

[0090] The term "carbamyl," as used herein, refers to an -NHC(O)O- or -OC(O)NH- group in which a carbon atom is doubly bonded to one oxygen atom and singly bonded to a nitrogen and a second oxygen atom.

[0091] The terms "halo" or "halogen", used alone or in combination with other terms, refer to fluoro, chloro, bromo, and iodo. In some embodiments, "halo" refers to a halogen atom selected from F, Cl, or Br. In some embodiments, a halo group is F.

[0092] The term "haloalkyl," as used herein, refers to an alkyl group in which one or more of the hydrogen atoms are replaced by a halogen atom. n~m The term "haloalkyl" refers to a C alkyl group having n to m carbon atoms and at least 1 to {2(n to m)+1} halogen atoms. n~m In some embodiments, the halogen atoms are fluoro atoms. In some embodiments, the haloalkyl groups have 1 to 6 or 1 to 4 carbon atoms. Examples of haloalkyl groups include CF 3 , C 2 F 5 , CHF 2, C.H. 2 F, CCl 3 , CHCl 2 , C 2 Cl 5 In some embodiments, the haloalkyl group is a fluoroalkyl group.

[0093] The term "haloalkoxy", used alone or in combination with other terms, refers to a group of the formula -O-haloalkyl, where haloalkyl is as defined above. n~m The term "haloalkoxy" refers to a haloalkoxy group, where the haloalkyl group has n to m carbons. Examples of haloalkoxy groups include trifluoromethoxy. In some embodiments, the haloalkoxy group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0094] The term "oxo" or "oxy" refers to an oxygen atom as a divalent substituent, which when attached to carbon forms a carbonyl group, or when attached to a heteroatom forms a sulfoxide or sulfone group, or an N-oxide group. In some embodiments, heterocyclic groups can be optionally substituted with one or two oxo (=O) substituents.

[0095] The term "sulfonyl" refers to a sulfur atom doubly bonded to two oxygen atoms -SO 2 - refers to the group.

[0096] The term "sulfinyl" refers to the -SO- group in which a sulfur atom is double bonded to an oxygen atom.

[0097] The term "oxidized" in reference to a ring-forming N-atom refers to a ring-forming N-oxide.

[0098] The term "oxidized" in reference to a ring-forming S atom refers to a ring-forming sulfonyl or ring-forming sulfinyl.

[0099] The term "aromatic" refers to a carbocycle or heterocycle having one or more polyunsaturated rings with aromatic character (i.e., having (4n+2) delocalized π (pi) electrons, where n is an integer).

[0100] The term "aryl", used alone or in combination with other terms, refers to an aromatic hydrocarbon group which may be monocyclic or polycyclic (e.g., having two fused rings). n~m The term "aryl" refers to an aryl group having n to m ring carbon atoms. Aryl groups include, for example, phenyl, naphthyl, and the like. In some embodiments, an aryl group has 6 to about 10 carbon atoms. In some embodiments, an aryl group has 6 carbon atoms. In some embodiments, an aryl group has 10 carbon atoms. In some embodiments, an aryl group is phenyl. In some embodiments, an aryl group is naphthyl.

[0101] The term "heteroaryl" or "heteroaromatic", used alone or in combination with other terms, refers to a monocyclic or polycyclic aromatic heterocycle having at least one heteroatom ring member selected from sulfur, oxygen, and nitrogen. In some embodiments, the heteroaryl ring has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. In some embodiments, any ring-forming N in the heteroaryl moiety may be an N-oxide. In some embodiments, the heteroaryl has 5-14 ring atoms and includes carbon atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. In some embodiments, the heteroaryl has 5-10 ring atoms and includes carbon atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. In some embodiments, the heteroaryl has 5-6 ring atoms and 1 or 2 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. In some embodiments, the heteroaryl is a 5- or 6-membered heteroaryl ring. In other embodiments, the heteroaryl is an 8-, 9-, or 10-membered fused bicyclic heteroaryl ring. Examples of heteroaryl groups include, but are not limited to, pyridinyl (pyridyl), pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, azolyl, oxazolyl, isoxazolyl, thiazolyl, imidazolyl, furanyl, thiophenyl, quinolinyl, isoquinolinyl, naphthyridinyl (including 1,2-, 1,3-, 1,4-, 1,5-, 1,6-, 1,7-, 1,8-, 2,3-, and 2,6-naphthyridine), indolyl, isoindolyl, benzothiophenyl, benzofuranyl, benzisoxazolyl, imidazo[1,2-b]thiazolyl, purinyl, and the like. In some embodiments, the heteroaryl group is a pyridone (e.g., 2-pyridone). In some embodiments, the heteroaryl group is chromanyl.

[0102] A 5-membered heteroaryl ring is a heteroaryl group having 5 ring atoms, where one or more (e.g., 1, 2 or 3) ring atoms are independently selected from N, O and S. Exemplary 5-membered heteroaryls include thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl, 1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl.

[0103] A 6-membered heteroaryl ring is a heteroaryl group having 6 ring atoms, where one or more (e.g., 1, 2, or 3) ring atoms are independently selected from N, O, and S. Exemplary 6-membered heteroaryls are pyridyl, pyrazinyl, pyrimidinyl, triazinyl, isoindolyl, and pyridazinyl.

[0104] The term "cycloalkyl", used alone or in combination with other terms, refers to non-aromatic hydrocarbon ring systems (monocyclic, bicyclic or polycyclic) including cyclized alkyl and alkenyl groups. n~m The term "cycloalkyl" refers to a cycloalkyl having n to m ring carbon atoms. Cycloalkyl groups can include monocyclic or polycyclic (e.g., having 2, 3 or 4 fused rings) groups and spirocycles. Cycloalkyl groups can have 3, 4, 5, 6 or 7 ring carbons (C 3~7 In some embodiments, the cycloalkyl group has 3 to 6 ring members, 3 to 5 ring members, or 3 to 4 ring members. In some embodiments, the cycloalkyl group is monocyclic. In some embodiments, the cycloalkyl group is monocyclic or bicyclic. In some embodiments, the cycloalkyl group is C 3~6It is a monocyclic cycloalkyl group. Optionally, the ring-forming carbon atoms of the cycloalkyl group may be oxidized to form an oxo or sulfido group. Cycloalkyl groups also include cycloalkylidene. In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. Moieties having one or more aromatic rings fused to (i.e., having a common bond with) a cycloalkyl ring, e.g., benzo or thienyl derivatives such as cyclopentane, cyclohexane, etc., are also included in the definition of cycloalkyl. Cycloalkyl groups containing fused aromatic rings may be bonded through any ring-forming atom, including the ring-forming atoms of the fused aromatic ring. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbornyl, norpinyl, norcarnyl, bicyclo[1.1.1]pentanyl, bicyclo[2.1.1]hexanyl, etc. In some embodiments, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0105] The term "heterocycloalkyl", used alone or in combination with other terms, refers to a non-aromatic ring or ring system having 4 to 10 ring members, 4 to 7 ring members, or 4 to 6 ring members, which may optionally contain one or more alkenylene groups as part of the ring structure and have at least one heteroatom ring member independently selected from nitrogen, sulfur, oxygen, and phosphorus. The term "heterocycloalkyl" includes monocyclic 4-, 5-, 6-, and 7-membered heterocycloalkyl groups. Heterocycloalkyl groups may include monocyclic or bicyclic (e.g., having 2 fused or bridged rings) or spirocyclic ring systems. In some embodiments, heterocycloalkyl groups are monocyclic groups having 1, 2, or 3 heteroatoms independently selected from nitrogen, sulfur, and oxygen. Ring-forming carbon atoms and heteroatoms of a heterocycloalkyl group are optionally oxidized to oxo or sulfide groups or other oxidized bonds (e.g., C(O), S(O), C(S), or S(O)). 2 , N-oxide, etc.) or the nitrogen atom may be quaternized. Heterocycloalkyl groups may be bonded through a ring-forming carbon atom or a ring-forming heteroatom. In some embodiments, heterocycloalkyl groups contain zero to three double bonds. In some embodiments, heterocycloalkyl groups contain zero to two double bonds. Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a common bond) to the heterocycloalkyl ring, such as benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. Heterocycloalkyl groups that contain fused aromatic rings may be bonded through any ring-forming atom, including the ring-forming atoms of the fused aromatic rings. Examples of heterocycloalkyl groups include 2,5-diazobicyclo[2.2.1]heptanyl; pyrrolidinyl; hexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl; 1,6-dihydropyridinyl; morpholinyl; azetidinyl; piperazinyl; and 4,7-diazaspiro[2.5]octan-7-yl.

[0106] In certain places, definitions or embodiments refer to certain rings (e.g., azetidine ring, pyridine ring, etc.).Unless otherwise indicated, these rings may be bonded to any ring member, but not beyond the valence of the atom.For example, the azetidine ring may be bonded at any position of the ring, while the azetidin-3-yl ring is bonded at the 3-position.

[0107] The compounds described herein may be asymmetric (e.g., have one or more stereocenters). All stereoisomers, e.g., enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods for preparing optically active forms from optically inactive starting materials are known in the art, for example, by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, such as C=N double bonds, may also exist in the compounds described herein, and all such stable isomers are contemplated in the present disclosure. Cis and trans geometric isomers of the compounds of the present disclosure are described and can be isolated as a mixture of isomers or as separated isomeric forms.

[0108] The resolution of a racemic mixture of compounds can be carried out by any of many methods known in the art. One method is fractional recrystallization using a chiral resolving acid that is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization are, for example, optically active acids, such as tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, or various optically active camphorsulfonic acids, such as the D and L forms of β-camphorsulfonic acid. Other suitable resolving agents for fractional crystallization include stereoisomerically pure forms of α-methyl-benzylamine (e.g., S and R forms, or diastereomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane, and the like.

[0109] Resolution of racemic mixtures may be accomplished by elution through a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). The composition of suitable elution solvents can be determined by one skilled in the art.

[0110] In some embodiments, the compounds disclosed herein have the (R) configuration. In other embodiments, the compounds have the (S) configuration. In compounds with more than one chiral center, each chiral center in the compound may be independently (R) or (S) unless otherwise indicated.

[0111] The compounds of the present disclosure also include tautomers. Tautomers result from the exchange of a single bond with an adjacent double bond along with the migration of a proton. Tautomers include prototropic tautomers, which are isomeric protonation states with the same empirical formula and total charge. Examples of prototropic tautomers include ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, enamine-imine pairs, and cyclic forms in which a proton can occupy more than one position in a heterocyclic ring system, such as 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomers may be in equilibrium or sterically fixed in one form by appropriate substitution.

[0112] The compounds disclosed herein may also include all isotopes of atoms occurring in intermediates or final compounds. Isotopes include atoms with the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium. One or more constituent atoms of the compounds of the present disclosure may be replaced or substituted with an atomic isotope in natural or non-natural abundance. In some embodiments, the compounds include at least one deuterium atom. For example, one or more hydrogen atoms in the compounds of the present disclosure may be replaced or substituted with deuterium. In some embodiments, the compounds include two or more deuterium atoms. In some embodiments, the compounds include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 deuterium atoms. Synthetic methods for incorporating isotopes into organic compounds are known in the art (Deuterium Labeling in Organic Chemistry by Alan F. Thomas (New York, NY, Appleton-Century-Crofts, 1971; The Renaissance of H / D Exchange by Jens Atzrodt, Volker Derdau, Thorsten Fey and Jochen Zimmermann, Angew. Chem. Int. Ed. 2007, 7744-7765; The Organic Chemistry of Isotopic Labelling by James R. Hanson, Royal Society of Chemistry, 2011). Isotopically labeled compounds can be used in a variety of studies, e.g., NMR spectroscopy, metabolic experiments, and / or assays.

[0113] Substitution with heavier isotopes, such as deuterium, may confer certain therapeutic advantages due to superior metabolic stability, e.g., increased in vivo half-life or reduced dosage requirements, and therefore may be preferred in some circumstances (A. Kerekes et.al. J. Med. Chem. 2011, 54, 201-210; R. Xu et.al. J. Label Compd. Radiopharm. 2015, 58, 308-312).

[0114] The term "compound" as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the depicted structures. The term is also meant to refer to compounds provided herein regardless of how they are prepared, for example, synthetically, via a biological process (e.g., metabolic or enzymatic conversion), or a combination thereof.

[0115] All compounds and their pharma- ceutically acceptable salts can be found together with other substances, such as water and solvents (e.g., hydrates and solvates) or can be isolated. When in the solid state, the compounds described herein and their salts can occur in various forms, for example, in the form of solvates, including hydrates. Compounds may be in any solid state form, such as polymorphs or solvates, and therefore, unless otherwise specified, references herein to compounds and their salts should be understood to include any solid state form of the compound.

[0116] In some embodiments, the compound disclosed herein or its salt is substantially isolated. "Substantially isolated" means that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation may include, for example, a composition enriched in the compound of the present invention. Substantial separation may include a composition that includes at least about 50% by weight, at least about 60% by weight, at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 95% by weight, at least about 97% by weight, or at least about 99% by weight of the compound disclosed herein or its salt.

[0117] The phrase "pharmacologically acceptable" is used herein to refer to compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals and without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0118] The expressions "ambient temperature" and "room temperature", as used herein, are understood in the art and generally refer to temperatures, e.g., reaction temperatures, which relate to the temperature of the room in which the reaction is carried out, e.g., a temperature of about 20° C. to about 30° C.

[0119] The present disclosure also includes pharma- ceutically acceptable salts of the compounds described herein. The term "pharma- ceutically acceptable salts" refers to derivatives of the disclosed compounds in which the parent compound has been modified by converting an existing acid or base moiety into its salt form. Examples of pharma- ceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues, such as amines; alkali or organic salts of acidic residues, such as carboxylic acids; and the like. The pharma- ceutically acceptable salts of the present disclosure include, for example, non-toxic salts of the parent compound formed from non-toxic inorganic or organic acids. The pharma- ceutically acceptable salts of the present disclosure may be synthesized from the parent compound containing a basic or acidic moiety by conventional chemical methods. In general, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent, or a mixture of the two; generally, non-aqueous media, such as ether, ethyl acetate, alcohols (e.g., methanol, ethanol, isopropanol, or butanol), or acetonitrile (MeCN) are preferred. A list of suitable salts can be found in Remington's Pharmaceutical Sciences 17, 19 ... th Ed., (Mack Publishing Company, Easton, 1985), p. 1418, Berge et al., J. Pharm. Sci., 1977, 66(1), 1-19, and Stahl et al., Handbook of Pharmaceutical Salts: Properties, Selection, and Use, (Wiley, 2002). In some embodiments, the compounds described herein include the N-oxide form.

[0120] synthesis The compounds provided herein, including their salts, can be prepared using known organic synthesis techniques, and may be synthesized according to any of a number of possible synthetic routes, for example, those in the following schemes.

[0121] The reaction for preparing the compounds of the present disclosure can be carried out in a suitable solvent, which can be easily selected by those skilled in the art of organic synthesis.A suitable solvent can be substantially non-reactive with the starting material (reactant), intermediate, or product at the temperature at which the reaction is carried out, which can range, for example, from the freezing temperature of the solvent to the boiling temperature of the solvent.A given reaction can be carried out in one solvent or a mixture of more than one solvent.Depending on the specific reaction step, a suitable solvent for a specific reaction step can be selected by those skilled in the art.

[0122] Preparation of the compounds provided herein may involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one of ordinary skill in the art. The chemistry of protecting groups can be found, for example, in Kocienski, Protecting Groups, (Thieme, 2007); Robertson, Protecting Group Chemistry, (Oxford University Press, 2000); Smith et al., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6 th Ed. (Wiley, 2007); Peturssion et al., “Protective Groups in Carbohydrate Chemistry,” J. Chem. Educ., 1997, 74(11), 1297; and Wuts et al., Protective Groups in Organic Synthesis, 4th Ed., (Wiley, 2006).

[0123] The reaction may be monitored according to any suitable method known in the art. For example, the formation of the product may be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., 1 H or 13C), infrared spectroscopy, spectrophotometry (eg, UV-visible), mass spectrometry, or by chromatographic methods such as high performance liquid chromatography (HPLC) or thin layer chromatography (TLC).

[0124] The following schemes provide general guidance related to the preparation of the compounds of the present disclosure. Those skilled in the art will understand that the preparations shown in the schemes can be modified or optimized using general knowledge of organic chemistry to prepare the various compounds provided herein.

[0125] [ka] Compounds of formula 1-22 and 1-23 can be prepared by the synthetic route outlined in Scheme 1. Starting material 1-1 can be iodinated with N-iodo-succinimide (NIS) to form intermediate 1-2, which can then be subjected to carbonylation conditions with palladium catalyst and carbon monoxide in methanol to give intermediate 1-3. Treatment of intermediate 1-3 with ethyl malonyl chloride can give compound 1-4, which can be cyclized in the presence of sodium ethoxide to give intermediate 1-5. Refluxing intermediate 1-5 in a mixture of concentrated hydrochloric acid and 1,4-dioxane can give compound 1-6. Nitration of compound 1-6 with nitric acid in acetic acid can give nitro compound 1-7, which can be cyclized in the presence of sodium ethoxide to give intermediate 1-5. 3 The intermediate 1-8 can be converted to the common intermediate 1-8 by the S-alkylation of the amine 1-9 (PG is a suitable protecting group, e.g., Boc). N The Ar reaction can be carried out to give compounds 1-10, which can be followed by one further S-thiomethoxide reaction. N The intermediates 1-11 can be subjected to Ar reaction to generate Boc protection and subsequent conversion of the nitro group to NH with a reducing agent (e.g., Fe powder or sodium dithionite). 2 Compound 1-13 can be prepared from intermediate 1-11 by reduction of the NH 2The group can be converted to an iodine atom under Sandmeyer reaction conditions to give intermediate 1-14, the Boc group of which can be removed with trifluoroacetic acid to give compound 1-15. The reaction of 1-15 with an alkyne of formula 1-16, where X is a hydrogen atom or an appropriately substituted metal [e.g., Sn(alkyl) 3

[0033] can be carried out under standard Sonogashira coupling conditions (e.g., in the presence of a palladium catalyst) or standard Stille cross-coupling conditions (e.g., in the presence of a palladium catalyst) to give intermediate 1-17, which can be cyclized to form a pyrrole ring in the presence of a gold catalyst to give compound 1-18. 1 M is a boronic acid, a boronic ester or a suitably substituted metal reagent, e.g., M is B(OR) 2 , Sn(alkyl) 3 , or Zn-Hal], or an NH-containing heterocycle) under standard Suzuki coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base), or under standard Stille cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Negishi cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Buchwald-Hartwig cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base) to prepare intermediate 1-20. Intermediate 1-20 can be prepared by oxidation of the sulfur group with a suitable oxidizing agent (e.g., m-CPBA) followed by the conversion of S N Ar reaction or by cross-coupling reactions (Org. Lett. 2002, 4, 979-981) to give the desired product 1-22. Alternatively, after removal of the protecting group in 1-21, the free amine can be capped (with various moieties) by electrophilic substitution, or reductive amination, or amide coupling, or cross-coupling reactions to give 1-23. The above chemical reaction sequences may be rearranged or omitted as appropriate to accommodate the preparation of different analogs.

[0126] [ka] Compounds of formula 2-10 can be prepared by the synthetic route outlined in Scheme 2. S-alkylation of intermediate 1-8 with amine 2-1 (PG is a suitable protecting group, e.g., Boc). N The Ar reaction can be carried out to give compound 2-2, which can be followed by one further S-thiomethoxide reaction. N The intermediate 2-3 can be reacted with Ar to give the nitro group to NH with a reducing agent (e.g., Fe powder or sodium dithionite). 2 Compounds 2-4 can be prepared from intermediate 2-3 by reduction to aldehyde 2-5. Cyclization between 2-4 and aldehyde 2-5 can generate intermediate 2-6, which can be converted to an adduct of formula 2-7 (wherein Cy is an alkyl group) under standard Suzuki coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base), or under standard Stille cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Negishi cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Buchwald-Hartwig cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base). 1 M is a boronic acid, a boronic ester or a suitably substituted metal reagent, e.g., M is B(OR) 2 , Sn(alkyl) 3 , or Zn-Hal], or an NH-containing heterocycle) to give compounds 2-8. Oxidation of the sulfur group with a suitable oxidizing agent (e.g., m-CPBA) followed by S NIntermediate 2-9 can be prepared from 2-8 by Ar reaction or by cross-coupling reaction (Org. Lett. 2002, 4, 979-981). Removal of the protecting group in 2-9 can give the desired product 2-10. The free NH group in 2-10 can also be capped with various moieties as illustrated in Scheme 1. The sequence of the above chemical reactions can be rearranged or omitted as appropriate to accommodate the preparation of different analogs.

[0127] [ka] Compounds of formula 3-9 can be prepared by the synthetic route outlined in Scheme 3. S-alkylation of intermediate 1-8 with amine 3-1 (PG is a suitable protecting group, e.g., Boc). N A further S-Ar reaction can be carried out to give compound 3-2, which can be followed by one S-Ar reaction with a nucleophile Nu-H [e.g., an amine, alcohol, or phenol]. N The intermediate 3-3 can be reacted with Ar to give the nitro group to NH with a reducing agent (e.g., Fe powder or sodium dithionite). 2 Compounds 3-4 can be prepared from intermediate 3-3 by reduction to C. Cyclization between 3-4 and aldehydes 3-5 can generate intermediates 3-6, which can be converted to adducts of formula 3-7 (wherein Cy is an alkyl group) under standard Suzuki coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base), or standard Stille cross-coupling conditions (e.g., in the presence of a palladium catalyst), or standard Negishi cross-coupling conditions (e.g., in the presence of a palladium catalyst), or standard Buchwald-Hartwig cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base). 1 M is a boronic acid, a boronic ester or a suitably substituted metal reagent, e.g., M is B(OR) 2 , Sn(alkyl) 3, or Zn-Hal], or NH-containing heterocycles) to give compounds 3-8. Removal of the protecting groups in 3-8 can give the desired products 3-9. The free NH group in 3-9 can also be capped with various moieties as illustrated in Scheme 1. The sequence of the above chemical reactions may be rearranged or omitted as appropriate to accommodate the preparation of different analogs.

[0128] [ka] Compounds of formula 4-9 can be prepared by the synthetic route outlined in Scheme 4. S-alkylation of intermediate 1-8 with amine 4-1 (PG is a suitable protecting group, e.g., Boc). N The Ar reaction can be carried out to give compound 4-2, which can be followed by one further S-thiomethoxide reaction. N The intermediate 4-3 can be reacted with Ar to give the nitro group to NH with a reducing agent (e.g., Fe powder or sodium dithionite). 2 Compound 4-4 can be prepared from intermediate 4-3 by reduction of intermediate 4-4 to NaNO in acetic acid. 2 Treatment of 4-5 with an adduct of formula 4-6 (wherein Cy 1 M is a boronic acid, a boronic ester or a suitably substituted metal reagent, e.g., M is B(OR) 2 , Sn(alkyl) 3, or Zn-Hal], or NH-containing heterocycle) under standard Suzuki coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base), or under standard Stille cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Negishi cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Buchwald-Hartwig cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base) to prepare compound 4-7. Compound 4-7 can be prepared by oxidation of the sulfur group with a suitable oxidizing agent (e.g., m-CPBA) followed by S N Ar reaction or by cross-coupling reaction (Org. Lett. 2002, 4, 979-981) to give 4-8. Removal of the protecting group in 4-8 can give intermediate 4-9. The free NH group in 4-9 can also be capped with various moieties as illustrated in Scheme 1. The sequence of the above chemical reactions can be rearranged or omitted as appropriate to accommodate the preparation of different analogs.

[0129] [ka] Compounds of formula 5-20 can be prepared by the synthetic route outlined in Scheme 5. Starting material 5-1 is halogenated with a suitable reagent, such as N-chloro-succinimide (NCS), N-bromo-succinimide (NBS) or N-iodo-succinimide (NIS) to give intermediate 5-2 (Hal is a halide, such as F, Cl, Br or I). Compound 5-4 can then be prepared by amide coupling reaction of 5-2 with a suitable acyl chloride 5-3. Condensation of 5-4 followed by decarboxylation can give intermediate 5-6. Nitration of intermediate 5-6 gives nitro adduct 5-7, which can be prepared by reaction with POCl. 3 Treatment with a reagent such as 5-6 affords intermediate 5-8. Treatment of 5-8 with an amine of formula 5-9 (PG is a suitable protecting group, e.g., Boc) affords intermediate 5-8. NAr reaction, followed by one more S reaction with another nucleophile N With Ar, compounds 5-11 are generated. The nitro functionality in 5-11 can be converted to -NH 2 to intermediate 5-13, which can then be reduced to intermediate 5-14 by cyclization to give compound 5-13. N Ar reaction) to a suitable coupling partner (here, Cy 1 M is a boronic acid, a boronic ester or a suitably substituted metal reagent, e.g., M is B(OR) 2 , Sn(alkyl) 3 , or Zn-Hal, Li, Na, K], or NH-containing heterocycles) under standard Suzuki coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base), or under standard Stille cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Negishi cross-coupling conditions (e.g., in the presence of a palladium catalyst), or under standard Buchwald-Hartwig cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable base), to prepare compound 5-19. Removal of the protecting group in 5-19 gives the desired product 5-20. The free NH group in 5-20 can also be capped with various moieties as illustrated in Scheme 1. The sequence of the above chemical reactions may be rearranged or omitted as appropriate to accommodate the preparation of different analogs.

[0130] KRAS protein The Ras family consists of three members: KRAS, NRAS, and HRAS. RAS-mutated cancers account for approximately 25% of human cancers. KRAS is the most frequently mutated isoform in human cancers: 85% of all RAS mutations are in KRAS, 12% in NRAS, and 3% in HRAS (Simanshu, D. et al. Cell 170.1 (2017): 17-33). KRAS mutations are prevalent among the top three most lethal cancer types: pancreatic (97%), colorectal (44%), and lung (30%) (Cox, AD et al. Nat Rev Drug Discov (2014) 13: 828-51). The majority of RAS mutations occur at amino acid residues / codons 12, 13, and 61; mutations in codon 12 occur most frequently in KRAS. The frequency of certain mutations varies between RAS genes, with G12D mutations being the most prevalent in KRAS, while Q61R and G12R mutations occur most frequently in NRAS and HRAS. Furthermore, the spectrum of mutations in RAS isoforms differs between cancer types. For example, KRAS G12D mutations predominate in pancreatic cancer (51%), followed by colorectal adenocarcinoma (45%) and lung cancer (17%) (Cox, AD et al. Nat Rev Drug Discov (2014) 13:828-51). In contrast, KRAS G12C mutations predominate in non-small cell lung cancer (NSCLC) (where nearly half of mutant KRAS are G12C), accounting for 11-16% of lung adenocarcinomas and 2-5% of pancreatic and colorectal adenocarcinomas, respectively (Cox, AD et al. Nat. Rev. Drug Discov. (2014) 13:828-51a). Using shRNAs to knock down thousands of genes across hundreds of cancer cell lines, genomic studies have demonstrated that cancer cells exhibiting KRAS mutations are highly dependent on KRAS function to grow cells (McDonald, R. et al. Cell 170 (2017):577-592). Taken together, these findings suggest that KRAS mutations play a critical role in human cancers, and thus the development of inhibitors targeting mutant KRAS may be useful in the clinical treatment of diseases characterized by KRAS mutations.

[0131] How to use Cancer types involving KRAS, including G12C, G12V and G12D mutations, include, but are not limited to, adenocarcinomas (e.g., pancreatic, colorectal, lung, bladder, stomach, esophagus, breast, head and neck, neck skin, thyroid); hematopoietic malignancies (e.g., myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic and juvenile myelomonocytic leukemia (CMML and JMML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and multiple myeloma (MM)); and other neoplasms (e.g., glioblastoma and sarcoma). Additionally, KRAS mutations have been associated with acquired resistance to anti-EGFR therapy (Knickelbein, K. et al. Genes & Cancer, (2015): 4-12). KRAS mutations have been found in immunological and inflammatory disorders (Fernandez-Medarde, A. et al. Genes & Cancer, (2011):344-358), such as Ras-associated lymphoproliferative disorder (RALD) or juvenile myelomonocytic leukemia (JMML), which are caused by somatic mutations in KRAS or NRAS.

[0132] The compound of the present disclosure can inhibit the activity of KRAS protein.For example, the compound of the present disclosure can be used to inhibit the activity of KRAS in cells or individuals or patients that require enzyme inhibition by administering to cells, individuals or patients an inhibitory amount of one or more compounds of the present disclosure.

[0133] As KRAS inhibitors, the compounds of the present disclosure are useful in treating various diseases associated with abnormal expression or activity of KRAS. Compounds that inhibit KRAS will be useful in providing a means of blocking growth or apoptosis induction in tumors, or by inhibiting angiogenesis. As a result, it is expected that the compounds of the present disclosure will prove useful in treating or blocking proliferative disorders, such as cancer. In particular, tumors with activated mutants of receptor tyrosine kinases or upregulation of receptor tyrosine kinases may be particularly sensitive to inhibitors.

[0134] In one aspect, provided herein is a method for inhibiting KRAS activity, comprising contacting a compound of the present disclosure with KRAS. In some embodiments, the contacting comprises administering the compound to a patient.

[0135] In another aspect, the present disclosure provides a method for treating a disease or disorder associated with inhibition of KRAS interaction, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of any of the formulas disclosed herein, or a pharma- ceutically acceptable salt thereof.

[0136] In one embodiment, the disease or disorder is an immune or inflammatory disorder.

[0137] In another embodiment, the immune or inflammatory disorder is a Ras-associated lymphoproliferative disorder caused by somatic mutations in KRAS and juvenile myelomonocytic leukemia.

[0138] In one aspect, the present disclosure provides a method for treating a disease or disorder associated with inhibition of a KRAS protein having a G12C mutation, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of any of the formulas disclosed herein, or a pharma- ceutically acceptable salt thereof.

[0139] In another aspect, the present specification provides a method of treating cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound disclosed herein, wherein the cancer is characterized by interaction with a KRAS protein having a G12C mutation.

[0140] In another aspect, the present disclosure provides a method for treating a disease or disorder associated with inhibition of a KRAS protein having a G12D mutation, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of any of the formulas disclosed herein, or a pharma- ceutically acceptable salt thereof.

[0141] In yet another aspect, the present specification also provides a method of treating cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound disclosed herein, wherein the cancer is characterized by interaction with a KRAS protein having a G12D mutation.

[0142] In another aspect, the present disclosure provides a method for treating a disease or disorder associated with inhibition of KRAS protein having a G12V mutation, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of any of the formulas disclosed herein, or a pharma- ceutically acceptable salt thereof.

[0143] In yet another aspect, the present specification also provides a method of treating cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound disclosed herein, wherein the cancer is characterized by interaction with a KRAS protein having a G12V mutation.

[0144] In yet another aspect, the present disclosure provides a method of treating cancer in a patient, comprising administering to the patient a therapeutically effective amount of any one of the compounds disclosed herein, or a pharma- ceutically acceptable salt thereof.

[0145] In one embodiment, the cancer is selected from carcinoma, hematological cancer, sarcoma, and glioblastoma.

[0146] In another embodiment, the hematological cancer is selected from myeloproliferative neoplasms, myelodysplastic syndromes, chronic and juvenile myelomonocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, and multiple myeloma.

[0147] In yet another embodiment, the carcinoma is selected from pancreatic cancer, colon cancer, lung cancer, bladder cancer, gastric cancer, esophageal cancer, breast cancer, head and neck cancer, cervical cancer, skin cancer, and thyroid cancer.

[0148] In another aspect, the present specification provides a method for treating a disease or disorder associated with inhibition of KRAS interaction or a mutant thereof in a patient in need thereof, comprising administering to the patient a compound disclosed herein, or a pharma- ceutically acceptable salt thereof, or a composition comprising a compound disclosed herein, or a pharma- ceutically acceptable salt thereof, in combination with another therapy or therapeutic agent described herein.

[0149] In one embodiment, the cancer is selected from hematological cancer, sarcoma, lung cancer, gastrointestinal cancer, genitourinary cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, and skin cancer.

[0150] In another embodiment, the lung cancer is selected from non-small cell lung cancer (NSCLC), small cell lung carcinoma, bronchogenic carcinoma, squamous cell bronchogenic carcinoma, undifferentiated small cell bronchogenic carcinoma, undifferentiated large cell bronchogenic carcinoma, adenocarcinoma, bronchogenic carcinoma, alveolar carcinoma, bronchiolar carcinoma, bronchial adenoma, chondromatous hamartoma, mesothelioma, papillary and nonpapillary carcinoma, bronchial adenoma, and pleuropulmonary blastoma.

[0151] In yet another embodiment, the lung cancer is non-small cell lung cancer (NSCLC). In yet another embodiment, the lung cancer is adenocarcinoma.

[0152] In one embodiment, the gastrointestinal cancer is selected from esophageal squamous cell carcinoma, esophageal adenocarcinoma, esophageal leiomyosarcoma, esophageal lymphoma, gastric carcinoma, gastric lymphoma, gastric leiomyosarcoma, exocrine pancreatic carcinoma, pancreatic ductal adenocarcinoma, pancreatic insulinoma, pancreatic glucagonoma, pancreatic gastrinoma, pancreatic carcinoid tumor, pancreatic vipoma, small intestinal adenocarcinoma, small intestinal lymphoma, small intestinal carcinoid tumor, Kaposi's sarcoma, small intestinal leiomyoma, small intestinal hemangioma, small intestinal lipoma, small intestinal neurofibroma, small intestinal fibroma, large intestinal adenocarcinoma, large intestinal tubular adenoma, large intestinal villous adenoma, large intestinal hamartoma, large intestinal leiomyoma, colorectal carcinoma, gallbladder carcinoma, and anal carcinoma.

[0153] In one embodiment, the gastrointestinal cancer is colorectal cancer.

[0154] In another embodiment, the cancer is a carcinoma. In yet another embodiment, the carcinoma is selected from pancreatic carcinoma, colorectal carcinoma, lung carcinoma, bladder carcinoma, gastric carcinoma, esophageal carcinoma, breast carcinoma, head and neck carcinoma, cervical skin carcinoma, and thyroid carcinoma.

[0155] In yet another embodiment, the cancer is a hematopoietic malignancy, hi one embodiment, the hematopoietic malignancy is selected from multiple myeloma, acute myeloid leukemia, and myeloproliferative neoplasms.

[0156] In another embodiment, the cancer is a neoplasm. In yet another embodiment, the neoplasm is a glioblastoma or a sarcoma.

[0157] In certain embodiments, the present disclosure provides a method for treating a KRAS-mediated disorder in a patient in need thereof, comprising administering to the patient a compound according to the present disclosure or a pharma- ceutical acceptable composition thereof.

[0158] In some embodiments, diseases and indications treatable using compounds of the present disclosure include, but are not limited to, hematological cancers, sarcomas, lung cancer, gastrointestinal cancer, genitourinary cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, and skin cancer.

[0159] Exemplary hematological cancers include lymphomas and leukemias, such as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, non-Hodgkin's lymphoma (including relapsed or refractory NHL and relapsed follicular), Hodgkin's lymphoma, myeloproliferative disorders, and myeloproliferative disorders. proliferative disorders (e.g., primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocytosis (ET), 8p11 myeloproliferative syndrome, myelodysplastic syndromes (MDS), T-cell acute lymphoblastic lymphoma (T-ALL), multiple myeloma, cutaneous T-cell lymphoma, adult T-cell leukemia, Waldenstrom's macroglubulinemia, hairy cell lymphoma, marginal zone lymphoma, chronic myelogenous lymphoma, and Burkitt's lymphoma).

[0160] Exemplary sarcomas include chondrosarcoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, myxoma, rhabdomyoma, rhabdomyosarcoma, fibroma, lipoma, hamartoma, lymphosarcoma, leiomyosarcoma, and teratoma.

[0161] Exemplary lung cancers include non-small cell lung cancer (NSCLC), small cell lung carcinoma, bronchogenic carcinoma (squamous cell, small undifferentiated cell, large undifferentiated cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, chondromatous hamartoma, mesothelioma, papillary and nonpapillary carcinoma, bronchial adenoma, and pleuropulmonary blastoma.

[0162] Exemplary gastrointestinal cancers include esophageal cancer (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), gastric cancer (carcinoma, lymphoma, leiomyosarcoma), pancreatic cancer (exocrine pancreatic carcinoma, ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestine cancer (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), colon cancer (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma), colorectal cancer, gallbladder cancer, and anal cancer.

[0163] Exemplary genitourinary cancers include renal carcinoma (adenocarcinoma, Wilms' tumor [nephroblastoma], renal cell carcinoma), bladder and urethral carcinoma (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate carcinoma (adenocarcinoma, sarcoma), testicular carcinoma (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma), and urothelial carcinoma.

[0164] Exemplary liver cancers include hepatocarcinoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, and hemangioma.

[0165] Exemplary bone cancers include, for example, osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondral osteoma (osteochondral exostosis), benign chondroma, chondroblastoma, chondromyxoid fibroma, osteoid osteoma, and giant cell tumor.

[0166] Exemplary nervous system cancers include cancer of the skull (osteoma, hemangioma, granuloma, xanthomas, osteitis deformans), meninges (meningioma, meningeal sarcoma, glioma), brain (astrocytoma, mesodermoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma, glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors, neuroectodermal tumors), and spinal cord (neurofibroma, meningioma, glioma, sarcoma), neuroblastoma, Lhermitte-Duclos disease, and pineal tumor.

[0167] Exemplary gynecologic cancers include cancer of the breast (ductal carcinoma, lobular carcinoma, breast sarcoma, triple-negative breast cancer, HER2-positive breast cancer, inflammatory breast cancer, papillary carcinoma), uterus (endometrial carcinoma), cervix (cervical carcinoma, preneoplastic cervical dysplasia), ovary (ovarian carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa cell tumor, Sertoli-Leydig cell tumor, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma), and fallopian tube (carcinoma).

[0168] Exemplary skin cancers include melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, Merkel cell skin cancer, moles dysplastic nevi, lipoma, hemangioma, dermatofibroma, and keloids.

[0169] Exemplary head and neck cancers include glioblastoma, melanoma, rhabdomyosarcoma, lymphosarcoma, osteosarcoma, squamous cell adenocarcinoma, adenocarcinoma, oral cancer, laryngeal cancer, nasopharyngeal cancer, nasal and paranasal sinus cancer, thyroid and parathyroid cancer, eye tumors, lip and mouth tumors, and squamous head and neck cancer.

[0170] Compounds of the present disclosure may also be useful in inhibiting tumor metastasis.

[0171] In addition to oncogenic neoplasms, the compounds of the present disclosure are useful in the treatment of skeletal and chondrocyte disorders, including, but not limited to, achondroplasia, hypochondroplasia, dwarfism, tophatogenic dysplasia (TD) (TDI and TDII clinical types), Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Bear-Stevenson cutis rotation syndrome, Pfeiffer syndrome, and craniosynostosis syndrome. In some embodiments, the present disclosure provides methods for treating patients suffering from skeletal and chondrocyte disorders.

[0172] In some embodiments, the compounds described herein can be used to treat Alzheimer's disease, HIV, or tuberculosis.

[0173] As used herein, the term "8p11 myeloproliferative syndrome" is meant to refer to myeloid / lymphoid neoplasms associated with hypereosinophilia and FGFR1 abnormalities.

[0174] As used herein, the term "cell" is meant to refer to a cell that exists in vitro, ex vivo, or in vivo. In some embodiments, an ex vivo cell may be part of a tissue sample excised from an organism, e.g., a mammal. In some embodiments, an in vitro cell may be a cell in cell culture. In some embodiments, an in vivo cell is a cell that is living within an organism, e.g., a mammal.

[0175] As used herein, the term "contacting" refers to bringing together the indicated moieties in an in vitro system or in vivo system.For example, "contacting" KRAS with the compound described herein includes administering the compound described herein to an individual or patient, such as a human, that has KRAS, as well as introducing the sample, such as the cell preparation or purified preparation that contains KRAS, into the compound described herein.

[0176] As used herein, the terms "individual," "subject," or "patient" are used interchangeably and refer to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses, or primates, most preferably humans.

[0177] As used herein, the phrase "therapeutically effective amount" refers to an amount of an active compound or pharmaceutical agent, such as any of the solid forms or salts thereof disclosed herein, that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is desired by a researcher, veterinarian, physician or other clinician. An appropriate "effective" amount in any particular case may be determined using techniques known to those of ordinary skill in the art.

[0178] The phrase "pharmacologically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals and free of undue toxicity, irritation, allergic response, immunogenicity or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0179] As used herein, the phrase "pharmaceutically acceptable carrier or excipient" refers to a pharma- ceutically acceptable material, composition, or vehicle, such as a liquid or solid excipient, diluent, solvent, or encapsulating material. Excipients or carriers are generally safe, non-toxic, and not otherwise biologically undesirable, and include excipients or carriers that are acceptable for veterinary use as well as human pharmaceutical use. In one embodiment, each component is "pharmaceutically acceptable" as defined herein. For example, Remington:The Science and Practice of Pharmacy,21st ed.;Lippincott Williams & Wilkins:Philadelphia,Pa.,2005;Handbook of Pharmaceutical Excipients,6th ed.;Rowe et al.,Eds.;The Pharmaceutical Press and the American Pharmaceutical Association:2009;Handbook of Pharmaceutical Additives,3rd ed.;Ash and Ash Eds.;Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC Press LLC: Boca Raton, Fla., 2009.

[0180] As used herein, the term "treating" or "treatment" refers to inhibiting a disease; e.g., inhibiting a disease, condition, or disorder in an individual experiencing or exhibiting a symptom or symptom of the disease, condition, or disorder (i.e., halting further progression of the symptom and / or symptom), or ameliorating a disease; e.g., ameliorating a disease, condition, or disorder in an individual experiencing or exhibiting a symptom or symptom of the disease, condition, or disorder (i.e., reversing the symptom and / or symptom), e.g., reducing the severity of a disease.

[0181] The terms "prevent," "preventing," or "prevention," as used herein, include preventing at least one symptom associated with or caused by the condition, disease, or disorder being prevented.

[0182] It is appreciated that certain features of the present disclosure, which are for clarity described in the context of separate embodiments, may also be provided in combination in a single embodiment (and the embodiments are intended to be combined as if described in a multiple sub-form). Conversely, various features of the present disclosure, which are for brevity described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

[0183] Combination therapy I. Cancer Therapy Cancer cell growth and survival may be affected by the failure of multiple signaling pathways. Therefore, combining inhibitors of different enzymes / proteins / receptors that exhibit different selectivity for the targets they modulate is useful for treating such conditions. Targeting multiple signaling pathways (or multiple biological molecules involved in a given signaling pathway) can reduce the possibility of drug resistance occurring in cell populations and / or mitigate the toxicity of treatment.

[0184] One or more additional pharmaceutical agents, such as chemotherapeutic agents, anti-inflammatory agents, steroids, immunosuppressants, immuno-oncology agents, metabolic enzyme inhibitors, chemokine receptor inhibitors, and phosphatase inhibitors, as well as targeted therapies, such as Bcr-Abl, Flt-3, EGFR, HER2, JAK, c-MET, VEGFR, PDGFR, c-Kit, IGF-1R, RAF, FAK, and CDK4 / 6 kinase inhibitors, such as those described in WO2006 / 056399, can be used in combination with the compounds of the present disclosure to treat a CDK2-related disease, disorder, or condition. Other agents, such as therapeutic antibodies, can be used in combination with the compounds of the present disclosure to treat a CDK2-related disease, disorder, or condition. One or more additional pharmaceutical agents can be administered to the patient simultaneously or sequentially.

[0185] In some embodiments, a CDK2 inhibitor is administered or used in combination with a BCL2 inhibitor or a CDK4 / 6 inhibitor.

[0186] The compounds disclosed herein can be combined with one or more other enzyme / protein / receptor inhibitor therapies for the treatment of diseases such as cancer and other diseases or disorders described herein. Examples of diseases and indications treatable with combination therapy include those described herein. Examples of cancer include solid tumors and non-solid tumors such as liquid tumors, hematological cancers, etc. Examples of infectious diseases include viral infections, bacterial infections, fungal infections, or parasitic infections. For example, the compounds disclosed herein can be combined with one or more inhibitors of the following kinases for the treatment of cancer: Akt1, Akt2, Akt3, BCL2, CDK4 / 6, TGF-βR, PKA, PKG, PKC, CaM kinase, phosphorylase kinase, MEKK, ERK, MAPK, mTOR, EGFR, HER2, HER3, HER4, INS-R, IDH2, IGF-1R, IR-R, PDGFαR, PDGFβR, PI3K (alpha, beta, gamma, delta, and multiple or selective), CSF1R, KIT, FLK-II, KDR / FLK-1, FLK-4, flt-1, FGFR1, FGFR2, FGFR3, FGFR4, c-Met, PARP, Ron, Sea, TRKA, TRKB, TRKC, TAM kinases (Axl, Mer, Tyro3), FLT3, VEGFR / Flt2, Flt4, EphA1, EphA2, EphA3, EphB2, EphB4, Tie2, Src, Fyn, Lck, Fgr, Btk, Fak, SYK, FRK, JAK, ABL, ALK, and B-Raf. In some embodiments, the compounds of the present disclosure can be combined with one or more of the following inhibitors for the treatment of cancer or infectious diseases: Non-limiting examples of inhibitors that can be combined with the compounds of the present disclosure for the treatment of cancer and infectious diseases include FGFR inhibitors (FGFR1, FGFR2, FGFR3, or FGFR4, e.g., pemigatinib (INCB54828), INCB62079), EGFR inhibitors (also known as ErB-1 or HER-1;e.g., erlotinib, gefitinib, vandetanib, orsimertinib, cetuximab, necitumumab, or panitumumab), VEGFR inhibitors or pathway blockers (e.g., bevacizumab, pazopanib, sunitinib, sorafenib, axitinib, regorafenib, ponatinib, cabozantinib, vandetanib, ramucirumab, lenvatinib, ziv-aflibercept), PARP inhibitors (e.g., e.g., olaparib, rucaparib, veliparib, or niraparib), JAK inhibitors (JAK1 and / or JAK2, e.g., ruxolitinib or baricitinib; or JAK1, e.g., itacitinib (INCB39110), INCB052793, or INCB054707), IDO inhibitors (e.g., epacadostat, NLG919, or BMS-986205, MK7162), LSD1 inhibitors (e.g., GSK2979552, INCB59872, and INCB60003), TDO inhibitors, PI3K-delta inhibitors (e.g., palsaclisib (INCB50465) or INCB50797), PI3K-gamma inhibitors such as PI3K-gamma selective inhibitors, Pim inhibitors (e.g., INCB53914), CSF1R inhibitors, TAM receptor tyrosine kinases (Tyro-3, Axl, and Mer; e.g., INCB081776), adenosine receptor antagonists (e.g., A2a / A2b receptor antagonists), HPK1 inhibitors, chemokine receptor inhibitors (e.g., CCR2 or CCR5 inhibitors), SHP1 / 2 phosphatase inhibitors, histone deacetylase inhibitors (HDACs) such as HDAC8 inhibitors, angiogenesis inhibitors, interleukin receptor inhibitors, bromo and extra terminal family member inhibitors (e.g., bromodomain inhibitors or BET inhibitors, such as INCB54329 and INCB57643), c-MET inhibitors (e.g., capmatinib), anti-CD19 antibodies (e.g., tafasitamab), ALK2 inhibitors (e.g., INCB00928); or combinations thereof.

[0187] In some embodiments, the compounds or salts described herein are administered with a PI3Kδ inhibitor. In some embodiments, the compounds or salts described herein are administered with a JAK inhibitor. In some embodiments, the compounds or salts described herein are administered with a JAK1 or JAK2 inhibitor (e.g., baricitinib or ruxolitinib). In some embodiments, the compounds or salts described herein are administered with a JAK1 inhibitor. In some embodiments, the compounds or salts described herein are administered with a JAK1 inhibitor that is more selective than JAK2.

[0188] In addition, the compounds described herein can be used in combination with targeted therapies, such as c-MET inhibitors (e.g., capmatinib), anti-CD19 antibodies (e.g., tafasitamab), ALK2 inhibitors (e.g., INCB00928), or combinations thereof, to treat cancer and other proliferative diseases.

[0189] Examples of antibodies used in combination therapy include, but are not limited to, trastuzumab (e.g., anti-HER2), ranibizumab (e.g., anti-VEGF-A), bevacizumab (Avastin™, e.g., anti-VEGF), panitumumab (e.g., anti-EGFR), cetuximab (e.g., anti-EGFR), Rituxan (e.g., anti-CD20), and antibodies against c-MET.

[0190] One or more of the following agents may be used in combination with the compounds of the present disclosure, which are presented as a non-limiting list: cytostatic agents, cisplatin, doxorubicin, taxotere, taxol, etoposide, irinotecan, camptostar, topotecan, paclitaxel, docetaxel, epothilone, tamoxifen, 5-fluorouracil, methotrexate, temozolomide, cyclophosphamide, SCH 66336, R115777, L778,123, BMS 214662, IRESSA™ (gefitinib), TARCEVA™ (erlotinib), antibodies against EGFR, intron, ara-C, adriamycin, cytoxan, gemcitabine, uracil mustard, chlormethine, ifosfamide, melphalan, chlorambucil, pipobroman, triethylenemelamine, triethylenethiophosphoramine, busulfan, carmustine, lomustine, streptozocin, dacarbazine, floxuridine, cyta Rabin, 6-mercaptopurine, 6-thioguanine, fludarabine phosphate, oxaliplatin, leucovorin, ELOXATIN™ (oxaliplatin), pentostatin, vinblastine, vincristine, vindesine, bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, mithramycin, deoxycoformycin, mitomycin-C, L-asparaginase, teniposide 17.Alpha-ethynyl estradiol, diethylstilbestrol, testosterone, prednisone, fluoxymesterone, dromostanolone propionate, testolactone, megestrol acetate, methylprednisolone, methyltestosterone, prednisolone, triamcinolone, chlorotrianisene, hydroxyprogesterone, aminoglutethimide, estramustine, medroxyprogesterone acetate, leuprolide, flutamide, toremifene, goserelin, carboplatin, hydroxyurea, amsacrine, procarbazine, mitotane, mitoxantrone, levamisole, navelbine, anastrozole, letrazole, capecitabine, reloxafine, droloxafine, hexamethylmelamine, avastin, HERCEPTIN™ (trastuzumab ), BEXXAR™ (tositumomab), VELCADE™ (bortezomib), ZEVALIN™ (ibritumomab tiuxetan), TRISENOX™ (arsenic trioxide), XELODA™ (capecitabine), vinorelbine, porfimer, ERBITUX™ (cetuximab), thiotepa, altretamine, melphalan, trastuzumab, relozole, Fulvestrant, Exemestane, Ifosfamide, Rituximab, C225 (Cetuximab), Campath (Alemtuzumab), Clofarabine, Cladribine, Aphidicolin, Rituxan, Sunitinib, Dasatinib, Tezacitabine, Sml1, Fludarabine, Pentostatin, Triapine, Didox, Trimidox, Amidox, 3-AP, and MDL-101,731.

[0191] The compounds of the present disclosure can also be combined with other cancer treatment methods, such as chemotherapy, radiation therapy, tumor-targeted therapy, adjuvant therapy, immunotherapy, or surgery. Examples of immunotherapy include cytokine therapy (e.g., interferon, GM-CSF, G-CSF, IL-2), CRS-207 immunotherapy, cancer vaccines, monoclonal antibodies, bispecific or multispecific antibodies, antibody-drug conjugates, T-cell adoptive transfer, Toll receptor agonists, RIG-I agonists, oncolytic virus therapy, and immunomodulatory small molecules, including thalidomide or JAK1 / 2 inhibitors, PI3Kδ inhibitors, and the like. The compounds can be administered in combination with one or more anti-cancer agents, such as chemotherapeutic agents. Examples of chemotherapy agents include abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, anastrozole, arsenic trioxide, asparaginase, azacitidine, bevacizumab, bexarotene, baricitinib, bleomycin, bortezomib, intravenous busulfan, oral busulfan, calsterone, capecitabine, carboplatin, carmustine, cetuximab, chlorambucil, cisplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, dalteparin sodium, dasatinib, daunorubicin, decitabine, denileukin, denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, drostanolone propionate, and eculizumab. , epirubicin, erlotinib, estramustine, etoposide phosphate, etoposide, exemestane, fentanyl citrate, filgrastim, floxuridine, fludarabine, fluorouracil, fulvestrant, gefitinib, gemcitabine, gemtuzumab ozogamicin, goserelin acetate, histrelin acetate, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon alpha 2a, irinotecan, lapatinib tosylate hydrate, lenalidomide, letrozole, leucovorin, leuprorelin acetate, levamisole, lomustine, mechlorethamine, megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone,Nandrolone phenpropionate phenpropionate), nelarabine, nofetumomab, oxaliplatin, paclitaxel, pamidronic acid, panitumumab, pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin, pipobroman, plicamycin, procarbazine, quinacrine, rasburicase, rituximab, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinib maleate, tamoxifen, temozolomide, teniposide, testolactone, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat, and zoledronate.

[0192] Additional examples of chemotherapeutic agents include proteasome inhibitors (eg, bortezomib), thalidomide, revlimid, and DNA damaging agents such as melphalan, doxorubicin, cyclophosphamide, vincristine, etoposide, carmustine, and the like.

[0193] Examples of steroids include corticosteroids such as dexamethasone or prednisone.

[0194] Examples of Bcr-Abl inhibitors include imatinib mesylate (GLEEVAC™), nilotinib, dasatinib, bosutinib, and ponatinib, and pharmaceutically acceptable salts.Other suitable examples of Bcr-Abl inhibitors include the genera and species of compounds disclosed in U.S. Patent No. 5,521,184, WO04 / 005281, and U.S. Application No. 60 / 578,491, and pharmaceutically acceptable salts thereof.

[0195] Examples of suitable Flt-3 inhibitors include midostaurin, lestaurtinib, linifanib, sunitinib, sunitinib, maleate, sorafenib, quizartinib, crenolanib, pacritinib, tanzutinib, PLX3397, and ASP2215, and pharmaceutically acceptable salts thereof. Examples of other suitable Flt-3 inhibitors include the compounds disclosed in WO03 / 037347, WO03 / 099771, and WO04 / 046120, and pharmaceutically acceptable salts thereof.

[0196] Examples of suitable RAF inhibitors include dabrafenib, sorafenib, and vemurafenib, and pharmaceutically acceptable salts thereof. Other suitable RAF inhibitors include the compounds disclosed in WO00 / 09495 and WO05 / 028444, and pharmaceutically acceptable salts thereof.

[0197] Examples of suitable FAK inhibitors include VS-4718, VS-5095, VS-6062, VS-6063, BI853520, and GSK2256098, and pharma- ceutically acceptable salts thereof. Other suitable FAK inhibitors include the compounds disclosed in WO04 / 080980, WO04 / 056786, WO03 / 024967, WO01 / 064655, WO00 / 053595, and WO01 / 014402, and pharma- ceutically acceptable salts thereof.

[0198] Examples of suitable CDK4 / 6 inhibitors include palbociclib, ribociclib, trilaciclib, relociclib, and abemaciclib, and pharmaceutically acceptable salts thereof. Examples of other suitable CDK4 / 6 inhibitors include compounds disclosed in WO09 / 085185, WO12 / 129344, WO11 / 101409, WO03 / 062236, WO10 / 075074, and WO12 / 061156, and pharmaceutically acceptable salts thereof.

[0199] In some embodiments, compounds of the present disclosure can be used in combination with one or more other kinase inhibitors, including imatinib, particularly for treating patients who are resistant to imatinib or other kinase inhibitors.

[0200] In some embodiments, the compounds of the present disclosure can be combined with chemotherapeutic agents in the treatment of cancer, and can improve the therapeutic response compared to the response to the chemotherapeutic agent alone without worsening the toxic effects of the chemotherapeutic agent. In some embodiments, the compounds of the present disclosure can be combined with chemotherapeutic agents as set forth herein. For example, additional pharmaceutical agents used in the treatment of multiple myeloma can include, but are not limited to, melphalan, melphalan + prednisone [MP], doxorubicin, dexamethasone, and Velcade (bortezomib). Further additional agents used in the treatment of multiple myeloma include Bcr-Abl, Flt-3, RAF, and FAK kinase inhibitors. In some embodiments, the agent is an alkylating agent, a proteasome inhibitor, a corticosteroid, or an immunomodulatory agent. Examples of alkylating agents include cyclophosphamide (CY), melphalan (MEL), and bendamustine. In some embodiments, the proteasome inhibitor is carfilzomib. In some embodiments, the corticosteroid is dexamethasone (DEX). In some embodiments, the immunomodulatory agent is lenalidomide (LEN) or pomalidomide (POM).A desirable result of the combination of a CDK2 inhibitor of the present disclosure with an additional agent is an additive or synergistic effect.

[0201] The agents may be combined with the compounds of the invention in a single or continuous release dosage form, or each agent may be administered simultaneously or sequentially in separate dosage forms.

[0202] The compounds of the present disclosure can be used in combination with one or more other inhibitors or one or more therapies for the treatment of infectious diseases, including viral, bacterial, fungal, or parasitic infections.

[0203] In some embodiments, a corticosteroid such as dexamethasone is administered to a patient in combination with a compound of the present disclosure, where the dexamethasone is administered intermittently rather than continuously.

[0204] The compounds of formula (I) or any of the formulas described herein, the compounds listed in any of the claims and described herein, or salts thereof, can be combined with other immunogenic agents, such as cancer cells, purified tumor antigens (including recombinant proteins, peptides, and carbohydrate molecules), cells, and cells transfected with genes encoding immune stimulating cytokines. Non-limiting examples of tumor vaccines that can be used include transfected tumor cells expressing melanoma antigens, such as peptides of gp100, MAGE antigens, Trp-2, MARTI, and / or tyrosinase, or the cytokine GM-CSF.

[0205] For cancer treatment, compounds of formula (I) or any of the formulas described herein, compounds listed in any of the claims and described herein, or salts thereof can be combined with vaccination protocols. In some embodiments, tumor cells are transduced to express GM-CSF. In some embodiments, tumor vaccines include proteins from viruses involved in human cancers, such as human papillomavirus (HPV), hepatitis viruses (HBV and HCV), and Kaposi's herpes sarcoma virus (KHSV). In some embodiments, compounds of the present disclosure can be combined with tumor-specific antigens, such as heat shock proteins isolated from the tumor tissue itself. In some embodiments, compounds of formula (I) or any of the formulas described herein, compounds listed in any of the claims and described herein, or salts thereof can be combined with dendritic cell immunotherapy to activate a strong anti-tumor response.

[0206] The compounds of the present disclosure can be combined with bispecific macrocyclic peptides that target Fe alpha receptor or Fe gamma receptor expressing effector cells to tumor cells. The compounds of the present disclosure can also be combined with macrocyclic peptides that activate host immune responsiveness.

[0207] In some further embodiments, the combination of the disclosed compounds with other therapeutic agents can be administered to a patient prior to, during, and / or after bone marrow or stem cell transplantation. The disclosed compounds can be used in combination with bone marrow transplantation for the treatment of various tumors of hematopoietic origin.

[0208] The compounds of formula (I) or any of the formulas described herein, the compounds listed in any of the claims and described herein, or their salts can be used in combination with vaccines to stimulate immune responses against pathogens, toxins, and self-antigens. Examples of pathogens for which this therapeutic approach may be particularly useful include those for which there is currently no effective vaccine or for which traditional vaccines are not completely effective. Such pathogens include, but are not limited to, HIV, hepatitis (A, B, C), influenza, herpes, giardia, malaria, leishmania, Staphylococcus aureus, and Pseudomonas Aeruginosa.

[0209] Viruses causing infectious diseases treatable by the methods of the present disclosure include, but are not limited to, human papillomavirus, influenza, hepatitis A, B, C or D virus, adenovirus, poxvirus, herpes simplex virus, human cytomegalovirus, severe acute respiratory syndrome virus, Ebola virus, measles virus, herpes virus (e.g., VZV, HSV-1, HAV-6, HSV-II, and CMV, Epstein-Barr virus), flavivirus, echovirus, rhinovirus, coxsackievirus, coronavirus, respiratory syncytial virus, mumps virus, rotavirus, measles virus, rubella virus, parvovirus, vaccinia virus, HTLV virus, dengue virus, papillomavirus, soft wart virus, poliovirus, rabies virus, JC virus, and arboviral encephalitis virus.

[0210] Pathogens causing infections treatable by the methods of the present disclosure include, but are not limited to, Chlamydia, Rickettsia, Mycobacteria, Staphylococcus, Streptococcus, Pneumococcus, Neisseria meningitidis and Conococcus, Klebsiella, Proteus, Serratia, Pseudomonas, Legionella, Corynebacterium diphtheriae, Salmonella, Bacillus, Vibrio cholera, Clostridium tetani, Clostridium botulinum, Bacillus anthracis, Plague, Leptospira, and Lyme burgdorferi.

[0211] Pathogenic fungi causing infections treatable by the methods of the present disclosure include, but are not limited to, Candida (e.g., albicans, krusei, glabrata, tropicalis), Cryptococcus neoformans, Aspergillus (e.g., fumigatus, niger), Genus Mucorales (e.g., mucor, absidia, rhizophus), Sporothrix schenkii, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Coccidioides immitis, and Histoplasma capsulatum.

[0212] Pathogenic parasites causing infections treatable by the methods of the present disclosure include, but are not limited to, Entamoeba histolytica, Balantidium coli, Naegleria fowleri, Acanthamoeba sp., Giardia lambia, Cryptosporidium sp., Pneumocystis carinii, Plasmodium vivax, Babesia microti, Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondi, and Nippostrongylus brasiliensis.

[0213] When multiple pharmaceutical agents are administered to a patient, they may be administered simultaneously, separately, sequentially, or in combination (eg, involving two or more agents).

[0214] Methods for safely and effectively administering most of these chemotherapeutic agents are known to those skilled in the art. In addition, their administration is described in standard texts. For example, the administration of many chemotherapeutic agents is described in the "Physicians' Desk Reference" (PDR, e.g., 1996 edition, Medical Economics Company, Montvale, NJ), the disclosure of which is incorporated herein by reference as if fully set forth.

[0215] II. Immune checkpoint therapy For the treatment of diseases such as cancer or infectious diseases, the compounds of the present disclosure can be used in combination with one or more immune checkpoint inhibitors. Examples of immune checkpoint inhibitors include inhibitors against immune checkpoint molecules such as CBL-B, CD20, CD28, CD40, CD70, CD122, CD96, CD73, CD47, CDK2, GITR, CSF1R, JAK, PI3K delta, PI3K gamma, TAM, arginase, HPK1, CD137 (also known as 4-1BB), ICOS, A2AR, B7-H3, B7-H4, BTLA, CTLA-4, LAG3, TIM3, TLR (TLR7 / 8), TIGIT, CD112R, VISTA, PD-1, PD-L1, and PD-L2. In some embodiments, the immune checkpoint molecule is a stimulatory checkpoint molecule selected from CD27, CD28, CD40, ICOS, OX40, GITR, and CD137. In some embodiments, the immune checkpoint molecule is an inhibitory checkpoint molecule selected from A2AR, B7-H3, B7-H4, BTLA, CTLA-4, IDO, KIR, LAG3, PD-1, TIM3, TIGIT, and VISTA. In some embodiments, the compounds provided herein can be used in combination with one or more agents selected from a KIR inhibitor, a TIGIT inhibitor, a LAIR1 inhibitor, a CD160 inhibitor, a 2B4 inhibitor, and a TGFR beta inhibitor.

[0216] In some embodiments, the compounds provided herein can be used in combination with one or more agonists of immune checkpoint molecules, such as OX40, CD27, GITR, and CD137 (also known as 4-1BB).

[0217] In some embodiments, the inhibitor of an immune checkpoint molecule is an anti-PD1 antibody, an anti-PD-L1 antibody, or an anti-CTLA-4 antibody.

[0218] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-1 or PD-L1, such as an anti-PD-1 or anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-1 or anti-PD-L1 antibody is selected from the group consisting of nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab, atezolizumab, avelumab, tislelizumab, spartalizumab (PDR001), cetrelimab (JNJ-63723283), toripalimab (JS001), camrelizumab (SHR-1210), sintilimab (IBI308), AB122 (GLS-010), AMP-224, AMP-514 / MEDI -0680, BMS936559, JTX-4014, BGB-108, SHR-1210, MEDI4736, FAZ053, BCD-100, KN035, CS1001, BAT1306, LZM009, AK105, HLX10, SHR-1316, CBT-502(TQB2450), A167(KL-A167), STI-A101(ZKAB001), CK-301, BGB-A333, MSB-2311, HLX20, TSR-042, or LY3300054.In some embodiments, the PD-1 or PD-L1 inhibitor is a compound described in U.S. Pat. Nos. 7,488,802, 7,943,743, 8,008,449, 8,168,757, 8,217,149, or 10,308,644; U.S. Publication Nos. 2017 / 0145025, 2017 / 0174671, 2017 / 0174679, No. 2017 / 0320875, No. 2017 / 0342060, No. 2017 / 0362253, No. 2018 / 0016260, No. 2018 / 0057486, No. 201 8 / 0177784, 2018 / 0177870, 2018 / 0179179, 2018 / 0179201, 2018 / 0179202, 2018 / 02 73519, 2019 / 0040082, 2019 / 0062345, 2019 / 0071439, 2019 / 0127467, 2019 / 0144439, 2019 / 0202824, 2019 / 0225601, 2019 / 0300524, or 2019 / 0345170; or PCT Publication No. WO03 042402, WO2008156712, WO2010089411, WO2010036959, WO2011066342, WO2011159877, WO2011082400, or WO2011161699, each of which is incorporated by reference in its entirety. In some embodiments, the PD-L1 inhibitor is INCB086550.

[0219] In some embodiments, the antibody is an anti-PD-1 antibody, such as an anti-PD-1 monoclonal antibody. In some embodiments, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, sintilimab, AB122, AMP-224, JTX-4014, BGB-108, BCD-100, BAT1306, LZM009, AK105, HLX10, or TSR-042. In some embodiments, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, or sintilimab. In some embodiments, the anti-PD-1 antibody is pembrolizumab. In some embodiments, the anti-PD-1 antibody is nivolumab. In some embodiments, the anti-PD-1 antibody is cemiplimab. In some embodiments, the anti-PD-1 antibody is spartalizumab. In some embodiments, the anti-PD-1 antibody is camrelizumab. In some embodiments, the anti-PD-1 antibody is cetrelimab. In some embodiments, the anti-PD-1 antibody is toripalimab. In some embodiments, the anti-PD-1 antibody is sintilimab. In some embodiments, the anti-PD-1 antibody is AB122. In some embodiments, the anti-PD-1 antibody is AMP-224. In some embodiments, the anti-PD-1 antibody is JTX-4014. In some embodiments, the anti-PD-1 antibody is BGB-108. In some embodiments, the anti-PD-1 antibody is BCD-100. In some embodiments, the anti-PD-1 antibody is BAT1306. In some embodiments, the anti-PD-1 antibody is LZM009. In some embodiments, the anti-PD-1 antibody is AK105. In some embodiments, the anti-PD-1 antibody is HLX10. In some embodiments, the anti-PD-1 antibody is TSR-042. In some embodiments, the anti-PD-1 monoclonal antibody is nivolumab or pembrolizumab. In some embodiments, the anti-PD-1 monoclonal antibody is MGA012 (INCMGA0012; retifanlimab). In some embodiments, the anti-PD1 antibody is SHR-1210.Other anti-cancer agent(s) include antibody therapeutics such as 4-1BB (e.g., urelumab, utomirumab). In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-L1, e.g., an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab, avelumab, durvalumab, tislelizumab, BMS-935559, MEDI4736, atezolizumab (MPDL3280A; also known as RG7446), avelumab (MSB0010718C), FAZ053, KN035, CS1001, SHR-1316, CBT-502, A167, STI-A101, CK-301, BGB-A333, MSB-2311, HLX20, or LY3300054. In some embodiments, the anti-PD-L1 antibody is atezolizumab, avelumab, durvalumab, or tislelizumab. In some embodiments, the anti-PD-L1 antibody is atezolizumab. In some embodiments, the anti-PD-L1 antibody is avelumab. In some embodiments, the anti-PD-L1 antibody is durvalumab. In some embodiments, the anti-PD-L1 antibody is tislelizumab. In some embodiments, the anti-PD-L1 antibody is BMS-935559. In some embodiments, the anti-PD-L1 antibody is MEDI4736. In some embodiments, the anti-PD-L1 antibody is FAZ053. In some embodiments, the anti-PD-L1 antibody is KN035. In some embodiments, the anti-PD-L1 antibody is CS1001. In some embodiments, the anti-PD-L1 antibody is SHR-1316. In some embodiments, the anti-PD-L1 antibody is CBT-502. In some embodiments, the anti-PD-L1 antibody is A167. In some embodiments, the anti-PD-L1 antibody is STI-A101. In some embodiments, the anti-PD-L1 antibody is CK-301. In some embodiments, the anti-PD-L1 antibody is BGB-A333. In some embodiments, the anti-PD-L1 antibody is MSB-2311. In some embodiments, the anti-PD-L1 antibody is HLX20. In some embodiments, the anti-PD-L1 antibody is LY3300054.

[0220] In some embodiments, the inhibitor of an immune checkpoint molecule is a small molecule that binds to PD-L1, or a pharma- ceutically acceptable salt thereof. In some embodiments, the inhibitor of an immune checkpoint molecule is a small molecule that binds to and internalizes PD-L1, or a pharma- ceutically acceptable salt thereof. In some embodiments, the inhibitor of an immune checkpoint molecule is a compound selected from those described in US2018 / 0179201, US2018 / 0179197, US2018 / 0179179, US2018 / 0179202, US2018 / 0177784, US2018 / 0177870, U.S. Patent Application No. 16 / 369,654 (filed March 29, 2019), and U.S. Patent Application No. 62 / 688,164, each of which is incorporated herein by reference in its entirety, or a pharma- ceutically acceptable salt thereof.

[0221] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of KIR, TIGIT, LAIR1, CD160, 2B4, and TGFRbeta.

[0222] In some embodiments, the inhibitor is MCLA-145.

[0223] In some embodiments, the inhibitor of the immune checkpoint molecule is an inhibitor of CTLA-4, such as an anti-CTLA-4 antibody. In some embodiments, the anti-CTLA-4 antibody is ipilimumab, tremelimumab, AGEN1884, or CP-675,206.

[0224] In some embodiments, the inhibitor of the immune checkpoint molecule is an inhibitor of LAG3, such as an anti-LAG3 antibody. In some embodiments, the anti-LAG3 antibody is BMS-986016, LAG525, INCAGN2385, or eftiragimodo alpha (IMP321).

[0225] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD73. In some embodiments, the inhibitor of CD73 is oleclumab.

[0226] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of TIGIT. In some embodiments, the inhibitor of TIGIT is OMP-31M32.

[0227] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of VISTA. In some embodiments, the inhibitor of VISTA is JNJ-61610588 or CA-170.

[0228] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of B7-H3. In some embodiments, the inhibitor of B7-H3 is enoblituzumab, MGD009, or 8H9.

[0229] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of KIR. In some embodiments, the inhibitor of KIR is lirilumab or IPH4102.

[0230] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of A2aR. In some embodiments, the inhibitor of A2aR is CPI-444.

[0231] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of TGF-beta. In some embodiments, the inhibitor of TGF-beta is travedersen, galcertinib, or M7824.

[0232] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PI3K-gamma. In some embodiments, the inhibitor of PI3K-gamma is IPI-549.

[0233] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD47. In some embodiments, the inhibitor of CD47 is Hu5F9-G4 or TTI-621.

[0234] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD73. In some embodiments, the inhibitor of CD73 is MEDI9447.

[0235] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD70. In some embodiments, the inhibitor of CD70 is cusatuzumab or BMS-936561.

[0236] In some embodiments, the inhibitor of the immune checkpoint molecule is an inhibitor of TIM3, such as an anti-TIM3 antibody. In some embodiments, the anti-TIM3 antibody is INCAGN2390, MBG453, or TSR-022.

[0237] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD20, such as an anti-CD20 antibody. In some embodiments, the anti-CD20 antibody is obinutuzumab or rituximab.

[0238] In some embodiments, the agonist of an immune checkpoint molecule is an agonist of OX40, CD27, CD28, GITR, ICOS, CD40, TLR7 / 8, and CD137 (also known as 4-1BB).

[0239] In some embodiments, the agonist of CD137 is urelumab. In some embodiments, the agonist of CD137 is utomirumab.

[0240] In some embodiments, the agonist of the immune checkpoint molecule is an inhibitor of GITR. In some embodiments, the agonist of GITR is TRX518, MK-4166, INCAGN1876, MK-1248, AMG228, BMS-986156, GWN323, MEDI1873, or MEDI6469. In some embodiments, the agonist of the immune checkpoint molecule is an agonist of OX40, such as an OX40 agonist antibody or an OX40L fusion protein. In some embodiments, the anti-OX40 antibody is INCAGN01949, MEDI0562 (tavolimab), MOXR-0916, PF-04518600, GSK3174998, BMS-986178, or 9B12. In some embodiments, the OX40L fusion protein is MEDI6383.

[0241] In some embodiments, the agonist of the immune checkpoint molecule is an agonist of CD40. In some embodiments, the agonist of CD40 is CP-870893, ADC-1013, CDX-1140, SEA-CD40, RO7009789, JNJ-64457107, APX-005M, or ChiLob7 / 4.

[0242] In some embodiments, the agonist of the immune checkpoint molecule is an agonist of ICOS. In some embodiments, the agonist of ICOS is GSK-3359609, JTX-2011, or MEDI-570.

[0243] In some embodiments, the agonist of the immune checkpoint molecule is an agonist of CD28. In some embodiments, the agonist of CD28 is celalizumab.

[0244] In some embodiments, the agonist of the immune checkpoint molecule is an agonist of CD27. In some embodiments, the agonist of CD27 is varlilumab.

[0245] In some embodiments, the agonist of the immune checkpoint molecule is an agonist of TLR7 / 8. In some embodiments, the agonist of TLR7 / 8 is MEDI9197.

[0246] The compounds of the present disclosure can be used in combination with bispecific antibodies. In some embodiments, one of the domains of the bispecific antibody targets PD-1, PD-L1, CTLA-4, GITR, OX40, TIM3, LAG3, CD137, ICOS, CD3, or TGFβ receptor. In some embodiments, the bispecific antibody binds to PD-1 and PD-L1. In some embodiments, the bispecific antibody that binds to PD-1 and PD-L1 is MCLA-136. In some embodiments, the bispecific antibody binds to PD-L1 and CTLA-4. In some embodiments, the bispecific antibody that binds to PD-L1 and CTLA-4 is AK104.

[0247] In some embodiments, the compounds of the present disclosure can be used in combination with one or more metabolic enzyme inhibitors.In some embodiments, the metabolic enzyme inhibitor is an inhibitor of IDO1, TDO, or arginase.Examples of IDO1 inhibitors include epacadostat, NLG919, BMS-986205, PF-06840003, IOM2983, RG-70099, and LY338196.Inhibitors of arginase inhibitors include INCB1158.

[0248] As noted throughout, the additional compounds, inhibitors, agents, etc. may be combined with the compounds of the invention in a single or continuous dosage form, or may be administered simultaneously or sequentially as separate dosage forms.

[0249] Formulation, Dosage Forms, and Administration When used as a pharmaceutical, the compounds of the present disclosure may be administered in the form of a pharmaceutical composition. Thus, the present disclosure provides a composition comprising a compound of formula I, II, or any of the formulas described herein, a compound listed in any of the claims and described herein, or a pharma- ceutically acceptable salt thereof, or any of these embodiments, and at least one pharma- ceutically acceptable carrier or excipient. These compositions may be prepared in a manner well known to those skilled in the art of medicine, and may be administered by various routes depending on the area to be treated, depending on whether the indicated treatment is localized or systemic. Administration may be topical (including transdermal, epidermal, ocular, and mucosal delivery, including intranasal, intravaginal, and intrarectal), pulmonary (e.g., by inhalation or insufflation of powder or aerosol, including by nebulizer; intratracheal or intranasal), or oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal, intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular administration. Parenteral administration may be in the form of a single bolus dose or, for example, by a continuous perfusion pump. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.

[0250] The present disclosure also includes pharmaceutical compositions comprising the compounds of the present disclosure or pharma- ceutically acceptable salts thereof as active ingredients in combination with one or more pharma- ceutically acceptable carriers or excipients. In some embodiments, the compositions are suitable for topical administration. In making compositions of the present disclosure, the active ingredient is typically mixed with an excipient, diluted by an excipient, or enclosed within a carrier, for example, in the form of a capsule, sachet, paper, or other container. When an excipient functions as a diluent, it may be a solid, semi-solid, or liquid material that acts as a vehicle, carrier, or medium for the active ingredient. Thus, the composition may be in the form of tablets, pills, powders, lozenges, sachets, oblates, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as solids or in liquid media), for example, ointments containing up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders.

[0251] In the preparation of the formulation, active compound can be milled to provide suitable particle size, and then combined with other ingredients.If active compound is substantially insoluble, it can be milled to a particle size of less than 200 mesh.If active compound is substantially water-soluble, particle size can be adjusted by milling to provide substantially uniform distribution in the formulation, for example, about 40 mesh.

[0252] The compounds provided herein may be milled using known milling procedures, such as wet milling, to obtain particle sizes suitable for tablet formation and other formulation types. Micronized (nanoparticulate) preparations of the compounds provided herein may be prepared by processes known in the art, see, for example, WO2002 / 000196.

[0253] Some examples of suitable additives include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methylcellulose.The formulation may further include lubricants such as talc, magnesium stearate and mineral oil; wetting agents; emulsifying and suspending agents; preservatives such as methyl- and propylhydroxy-benzoates; sweeteners; and flavoring agents.The composition of the present disclosure may be formulated to provide quick, sustained or delayed release of active ingredient after administration to a patient by using procedures known in the art.

[0254] In some embodiments, the pharmaceutical composition comprises silicified microcrystalline cellulose (SMCC) and at least one compound described herein or a pharma- ceutically acceptable salt thereof. In some embodiments, the silicified microcrystalline cellulose comprises about 98 w / w% microcrystalline cellulose and about 2 w / w% silicon dioxide.

[0255] In some embodiments, the composition is a sustained release composition comprising at least one compound described herein or a pharma- ceutically acceptable salt thereof, and at least one pharma- ceutically acceptable carrier or excipient. In some embodiments, the composition comprises at least one compound described herein or a pharma- ceutically acceptable salt thereof, and at least one component selected from microcrystalline cellulose, lactose monohydrate, hydroxypropyl methylcellulose, and polyethylene oxide. In some embodiments, the composition comprises at least one compound described herein or a pharma- ceutically acceptable salt thereof, and microcrystalline cellulose, lactose monohydrate, and hydroxypropyl methylcellulose. In some embodiments, the composition comprises at least one compound described herein or a pharma- ceutically acceptable salt thereof, and microcrystalline cellulose, lactose monohydrate, and polyethylene oxide. In some embodiments, the composition further comprises magnesium stearate or silicon dioxide. In some embodiments, the microcrystalline cellulose is Avicel PH102™. In some embodiments, the lactose monohydrate is Fast-flo316™. In some embodiments, the hydroxypropyl methylcellulose is hydroxypropyl methylcellulose 2208 K4M (e.g., Methocel K4 M Premier™) and / or hydroxypropyl methylcellulose 2208 K100LV (e.g., Methocel K00LV™). In some embodiments, the polyethylene oxide is polyethylene oxide WSR 1105 (e.g., Polyox WSR 1105™).

[0256] In some embodiments, the compositions are produced using a wet granulation process. In some embodiments, the compositions are produced using a dry granulation process.

[0257] The compositions may be formulated in unit dosage form, each dosage containing from about 5 to about 1,000 mg (1 g), more usually from about 100 mg to about 500 mg, of the active ingredient. In some embodiments, each dosage contains about 10 mg of the active ingredient. In some embodiments, each dosage contains about 50 mg of the active ingredient. In some embodiments, each dosage contains about 25 mg of the active ingredient. The term "unit dosage form" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with suitable pharmaceutical excipients.

[0258] The components used to formulate the pharmaceutical composition are of high purity and substantially free of potentially harmful contaminants (e.g., at least National Food grade, generally at least analytical grade, more typically at least pharmaceutical grade). Particularly for human consumption, the composition is preferably manufactured or formulated under Good Manufacturing Practice regulations as defined in applicable regulations of the U.S. Food and Drug Administration. For example, suitable formulations may be sterile and / or substantially isotonic, and / or in full compliance with all Good Manufacturing Practice regulations of the U.S. Food and Drug Administration.

[0259] The active compounds may be effective over a wide dosage range and are generally administered in a therapeutically effective amount. However, it will be understood that the amount of compound actually administered will usually be determined by the physician according to the appropriate circumstances, including the condition to be treated, the route of administration selected, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like.

[0260] The therapeutic dosage of the compounds of the present disclosure may vary, for example, according to the particular use for which the treatment is made, the mode of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of the compounds provided herein in a pharmaceutical composition may vary depending on a number of factors, including dosage amount, chemical properties (e.g., hydrophobicity), and route of administration. For example, the compounds disclosed herein may be provided in an aqueous physiological buffer solution containing about 0.1 to about 10% w / v of the compound for parenteral administration. Some typical dosage ranges are about 1 μg / kg to about 1 g / kg of body weight per day. In some embodiments, the dosage range is about 0.01 mg / kg to about 100 mg / kg of body weight per day. The dosage is likely to depend on variables, such as the type and extent of progression of the disease or disorder, the overall health of the particular patient, the relative biological availability of the selected compound, the formulation of excipients, and its route of administration. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0261] For the preparation of solid compositions, such as tablets, the main active ingredient is mixed with pharmaceutical additives to form a solid preformulation composition containing a homogeneous mixture of the compound of the present disclosure.When these preformulation compositions are referred to as homogeneous, the active ingredient is typically uniformly distributed throughout the composition, so that the composition can be easily and equally subdivided into effective unit dosage forms, such as tablets, pills and capsules.The solid preformulation is then subdivided into unit dosage forms of the above-mentioned type, such as containing about 0.1 to about 1000 mg of the active ingredient of the present disclosure.

[0262] The tablets or pills of the present disclosure may be coated or otherwise compounded to provide a dosage form that provides the advantage of prolonged action.For example, the tablet or pill may comprise an inner dosage and an outer dosage component, the latter being in the form of a coating over the former.The two components may be separated by an enteric layer that serves to resist disintegration in the stomach and allows the inner component to pass intact into the duodenum or be released in a delayed manner.Various materials may be used for such enteric layers or coatings, including a number of polymeric acids and mixtures of polymeric acids with materials such as shellac, cetyl alcohol and cellulose acetate.

[0263] Liquid forms into which the compounds and compositions of the present disclosure may be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oily suspensions, and emulsions flavored with edible oils, such as cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles.

[0264] Compositions for inhalation or insufflation include solutions and suspensions in pharma- ceutically acceptable, aqueous or organic solvents or mixtures thereof, as well as powders. Liquid or solid compositions may contain suitable pharma- ceutically acceptable additives as described above. In some embodiments, the compositions are administered by oral or nasal respiratory routes for localized or systemic effect. Compositions may be nebulized by using inert gases. Nebulized solutions may be breathed directly from the nebulizing device, which may be attached to a face mask, tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions may be administered orally or nasally from a device that delivers the formulation in an appropriate manner.

[0265] Topical formulations may include one or more conventional carriers. In some embodiments, ointments may include water and one or more hydrophobic carriers selected from, for example, liquid paraffin, polyoxyethylene alkyl ether, propylene glycol, white petrolatum, and the like. Cream carrier compositions may be based on water in combination with glycerol and one or more other components, for example, glycerol monostearate, PEG-glycerol monostearate, and cetylstearyl alcohol. Gels may be formulated using isopropyl alcohol and water in suitable combination with other components, for example, glycerol, hydroxyethylcellulose, and the like. In some embodiments, topical formulations include at least about 0.1, at least about 0.25, at least about 0.5, at least about 1, at least about 2, or at least about 5 wt% of a compound disclosed herein. Topical formulations may be suitably packaged, for example, in 100 g tubes, optionally associated with instructions for use to treat a selected indication, for example, psoriasis or other skin conditions.

[0266] The amount of compound or composition administered to a patient will vary depending on what is being administered, the purpose of the administration, e.g., prophylaxis or therapy, the condition of the patient, the mode of administration, etc. In therapeutic applications, the composition may be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. The effective dose will depend on the disease state being treated, and will be at the discretion of the attending clinician depending on factors such as the severity of the disease, the age, weight, and general condition of the patient, etc.

[0267] The compositions administered to a patient may be in the form of pharmaceutical compositions described above. These compositions may be sterilized by conventional aseptic techniques or sterile filtered. Aqueous solutions may be packaged or lyophilized for use as is, and lyophilized preparations are combined with sterile aqueous carriers before administration. The pH of the compound preparations will typically be between 3 and 11, more preferably between 5 and 9, and most preferably between 7 and 8. It will be understood that certain use of the above-mentioned additives, carriers, or stabilizers will result in the formation of pharmaceutical salts.

[0268] The therapeutic dosage of the compounds of the present disclosure may vary, for example, according to the particular use for which the treatment is made, the mode of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of the compounds of the present invention provided herein in a pharmaceutical composition may vary depending on a number of factors, including dosage amount, chemical properties (e.g., hydrophobicity), and route of administration. For example, the compounds of the present disclosure may be provided in an aqueous physiological buffer solution containing about 0.1 to about 10% w / v of the compound for parenteral administration. Some typical dosage ranges are about 1 μg / kg to about 1 g / kg of body weight per day. In some embodiments, the dosage range is about 0.01 mg / kg to about 100 mg / kg of body weight per day. The dosage is likely to depend on variables, such as the type and extent of progression of the disease or disorder, the overall health of the particular patient, the relative biological availability of the selected compound, the formulation of excipients, and its route of administration. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0269] Labeled Compounds and Assay Methods Another aspect of the present disclosure relates to the labeled (radiolabeled, fluorescently labeled, etc.) compounds of the present disclosure that will be useful in both in vitro and in vivo imaging techniques as well as assays for localizing and quantifying KRAS protein in tissue samples, including humans, and for identifying KRAS ligands by inhibiting the binding of the labeled compounds. Substitution of one or more atoms of the compounds of the present disclosure may also be useful in generating special ADME (adsorption, distribution, metabolism, and excretion). Thus, the present disclosure includes KRAS binding assays that include such labeled or substituted compounds.

[0270] The present disclosure further includes isotopically labeled compounds of the present disclosure. An "isotopically" or "radiolabeled" compound is a compound of the present disclosure in which one or more atoms have been replaced or substituted by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature (i.e., naturally occurring). Suitable radionuclides that may be incorporated into the disclosed compounds include, but are not limited to, 2 H (also written as D for deuterium), 3 H (also written as T for tritium), 11 C. 13 C. 14 C. 13 N, 15 N, 15 O. 17 O. 18 O. 18 F, 35 S, 36 Cl, 82 Br, 75 Br, 76 Br, 77 Br, 123 I, 124 I, 125 I and 131 For example, one or more hydrogen atoms in the compounds of the present disclosure may be replaced by a deuterium atom (e.g., C of formula I, II, or any formula provided herein). 1~6One or more hydrogen atoms of an alkyl group may be optionally replaced with a deuterium atom, e.g., -CD 3 Ha-CH 3 In some embodiments, the alkyl group of formula I, II, or any formula provided herein can be perdeuterated.

[0271] One or more constituent atoms of the compounds presented herein may be replaced or substituted with atomic isotopes in natural or non-natural abundance ratios. In some embodiments, the compounds contain at least one deuterium atom. In some embodiments, the compounds contain two or more deuterium atoms. In some embodiments, the compounds contain 1-2, 1-3, 1-4, 1-5, or 1-6 deuterium atoms. In some embodiments, all of the hydrogen atoms in the compounds may be replaced or substituted with deuterium atoms.

[0272] Synthetic methods for incorporating isotopes into organic compounds are known in the art (Deuterium Labeling in Organic Chemistry by Alan F. Thomas (New York, NY, Appleton-Century-Crofts, 1971; The Renaissance of H / D Exchange by Jens Atzrodt, Volker Derdau, Thorsten Fey and Jochen Zimmermann, Angew. Chem. Int. Ed. 2007, 7744-7765; The Organic Chemistry of Isotopic Labelling by James R. Hanson, Royal Society of Chemistry, 2011). Isotopically labeled compounds may be used in a variety of studies, e.g., NMR spectroscopy, metabolic experiments, and / or assays.

[0273] Substitution with heavier isotopes, such as deuterium, may provide certain therapeutic advantages due to superior metabolic stability, such as increased in vivo half-life or reduced dosage requirements, and may therefore be preferred in some circumstances. (See, for example, A. Kerekes et.al. J. Med. Chem. 2011, 54, 201-210; R. Xu et.al. J. Label Compd. Radiopharm. 2015, 58, 308-312). In particular, substitution at one or more metabolic sites may provide one or more of the therapeutic advantages.

[0274] The radionuclide incorporated in the present radiolabeled compounds will depend on the particular application of that radiolabeled compound. For example, for in vitro adenosine receptor labeling and competition assays: 3 H, 14 C. 82 Br, 125 I, 131 I or 35 Compounds incorporating S may be useful. For radioimaging applications, 11 C. 18 F, 125 I, 123 I, 124 I, 131 I, 75 Br, 76 Br or 77 Br may be useful.

[0275] A "radiolabel" or "labeled compound" is understood to be a compound into which at least one radionuclide has been incorporated. In some embodiments, the radionuclide is 3 H, 14 C. 125 I, 35 S and 82 Br.

[0276] The present disclosure may further include synthetic methods for incorporating radioisotopes into the compounds of the present disclosure. Synthetic methods for incorporating radioisotopes into organic compounds are well known in the art, and one of ordinary skill in the art would readily recognize methods applicable to the compounds of the present disclosure.

[0277] The labeled compounds of the present disclosure may be used in screening assays to identify and / or evaluate compounds. For example, a newly synthesized or identified labeled compound (i.e., test compound) can be evaluated for its ability to bind to KRAS protein by monitoring its concentration change when contacted with KRAS via tracking of the label. For example, a test compound (labeled) can be evaluated for its ability to reduce the binding of another compound (i.e., standard compound) that is known to bind to KRAS protein. Thus, the ability of the test compound to compete with the standard compound for direct binding to KRAS protein correlates with its binding affinity. Conversely, in some other screening assays, the standard compound is labeled and the test compound is not labeled. Thus, the concentration of the labeled standard compound is monitored to evaluate the competition between the standard compound and the test compound, thereby ascertaining the relative binding affinity of the test compound.

[0278] kit The present disclosure also includes pharmaceutical kits useful in treating or preventing diseases or disorders associated with the activity of KRAS, such as cancer or infectious diseases, which include one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I, II, or any of these embodiments. Such kits may further include one or more of various conventional pharmaceutical kit components, such as a container containing one or more pharma-ceutically acceptable carriers, additional containers, etc., as would be readily apparent to one skilled in the art. Instructions, either as an insert or label indicating the amount of components to be administered, guidelines for administration, and / or guidelines for mixing components may also be included in the kit.

[0279] The present disclosure will be described in more detail by specific examples.The following examples are provided for illustrative purposes and are not intended to limit the present disclosure in any way.Those skilled in the art will easily recognize various non-critical parameters that can be changed or modified to obtain substantially the same results.The compound of the example is found to inhibit the activity of KRAS according to at least one assay described herein. EXAMPLES

[0280] The experimental procedures for the compounds provided herein are provided below. Preparative LC-MS purification of some of the compounds prepared was carried out on a Waters mass-directed fractionation system. The basic instrument settings, protocols, and control software for the operation of these systems are described in detail in the literature. See, e.g., "Two-Pump At Column Dilution Configuration for Preparative LC-MS", K. Blom, J. Combi. Chem., 4, 295 (2002); "Optimizing Preparative LC-MS Configurations and Methods for Parallel Synthesis Purification", K. Blom, R. Sparks, J. Doughty, G. Everlof, T. Haque, A. Combs, J. Combi. Chem., 5, 670 (2003); and "Preparative LC-MS Purification: Improved Compound Specific Method Optimization", K. Blom, B. Glass, R. Sparks, A. Combs, J. Combi. Chem., 6, 874-883 (2004). Separated compounds are typically subjected to analytical liquid chromatography mass spectrometry (LCMS) to confirm purity.

[0281] The isolated compounds were typically subjected to analytical liquid chromatography mass spectrometry (LCMS) to confirm purity under the following conditions: Instrument: Agilent 1100 series, LC / MSD; Column: Waters Sunfire™ C 18 Particle size 5 μm, 2.1×5.0 mm, buffer: mobile phase A: 0.025% TFA in water and mobile phase B: acetonitrile; gradient 2% to 80% of B in 3 min at a flow rate of 2.0 mL / min.

[0282] Some of the prepared compounds were also separated on a preparative scale by reversed-phase high performance liquid chromatography (RP-HPLC) with MS detection or flash chromatography (silica gel) as shown in the examples. Typical preparative reversed-phase high performance liquid chromatography (RP-HPLC) column conditions are as follows:

[0283] pH=2 purification: Waters Sunfire(TM) C 18 Particle size 5 μm, 19×100 mm column, eluted with mobile phase A: 0.1% TFA (trifluoroacetic acid) in water and mobile phase B: acetonitrile; flow rate was 30 mL / min, separation gradient was optimized for each compound using compound specific method optimization protocol as described in literature [see “Preparative LCMS Purification: Improved Compound Specific Method Optimization”, K. Blom, B. Glass, R. Sparks, A. Combs, J. Comb. Chem., 6, 874-883 (2004)]. Typically, the flow rate used for the 30×100 mm column was 60 mL / min.

[0284] pH=10 Purification: Waters XBridge C 18 Particle size 5 μm, 19 × 100 mm column, mobile phase A: 0.15% NH in water 4OH and mobile phase B: acetonitrile; the flow rate was 30 mL / min, and the separation gradient was optimized for each compound using compound-specific method optimization protocols as described in the literature [see "Preparative LCMS Purification: Improved Compound Specific Method Optimization", K. Blom, B. Glass, R. Sparks, A. Combs, J. Comb. Chem., 6, 874-883 (2004)]. Typically, the flow rate used for a 30 x 100 mm column was 60 mL / min.

[0285] The following abbreviations may be used herein: AcOH (acetic acid); 2O(acetic anhydride);aq.(aqueous solution);atm.(atmosphere);Boc(t-butoxycarbonyl);br(broad);Cbz(carboxybenzyl);calc.(calculated value);d(doublet);dd(doublet of doublets);DBU(1,8-diazabicyclo[5.4.0]undec-7-ene);DCM(dichloromethane);DIAD(N,N'-diisopropylazidedicarboxylate);DIEA(N,N-diisopropylethylamine);DIBAL-H(diisobutylaluminium hydride) m(milligram);DMF(N,N-dimethylformamide);EtOH(ethanol);EtOAc(ethyl acetate);FCC(flash column chromatography);g(gram);h(hour);HATU(N,N,N',N'-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate);HCl(hydrochloric acid);HPLC(high performance liquid chromatography);Hz(hertz);J(coupling constant);LCMS(liquid chromatography-mass spectrometry);LDA(lithium diisopropylamide);m(multiplet);M(molar);mCPBA(3-chloroperoxybenzoic acid);MS(mass spectrometry);Me(methyl);MeCN(acetonitrile);MeOH(methanol);mg(milligram);min.(minute);mL(milliliter);mmol(millimolar);N(normal);NCS(N-chlorosuccinimide);NEt3(triethylamine);nM(nanomolar);NMP(N-methylpyrrolidone);NMR(nuclear magnetic resonance spectroscopy);OTf(trifluoromethyl) fluoromethanesulfonate; Ph (phenyl); pM (picomolar); PPT (precipitate); RP-HPLC (reverse-phase high-performance liquid chromatography); rt (room temperature); s (singlet); t (triplet or tertiary); TBS (tert-butyldimethylsilyl); tert (tertiary); tt (triplet of triplets); TFA (trifluoroacetic acid); THF (tetrahydrofuran); μg (microgram); μL (microliter); μM (micromolar); wt% (weight percent). Brine is saturated aqueous sodium chloride solution. in vacuo is under vacuum.

[0286] The compounds of the present disclosure may be isolated in either free base or pharmaceutical salt form.

[0287] Intermediate 1. 2,4,7-trichloro-8-fluoro-3-nitro-1,6-naphthyridine [ka]

[0288] Step 1. 2-Chloro-3-fluoro-5-iodopyridin-4-amine [ka] p-Toluenesulfonic acid monohydrate (1.1 g, 5.8 mmol) was added to a solution of 2-chloro-3-fluoropyridin-4-amine (17 g, 116 mmol) and NIS (31.3 g, 139 mmol) in acetonitrile (150 ml), and the resulting mixture was then stirred at 70° C. for...

Claims

1. Compounds of Formula I: 【Chemical 1】 or a pharmaceutically acceptable salt thereof (In the formula, 【Chemistry 2】 represents a single or double bond; -AR １ =BR ２ - is -N=CR ２ - and - CR １ =N-; X is N and CR ５ Selected from: Y is N and CR ６ Selected from: R １ H, D, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5-10 membered heteroaryl, halo, CN, OR ａ１ , S.R. ａ１ , C(O)R ｂ１ , C(O)NR ｃ１ R ｄ１ , C(O)OR ａ１ , O.C.(O.)R ｂ１ , OC(O)NR ｃ１ R ｄ１ , N.R. ｃ１ R ｄ１ , N.R. ｃ１ C(O)R ｂ１ , N.R. ｃ１ C(O)OR ａ１ , N.R. ｃ１ C(O)NR ｃ１ R ｄ１ , N.R. ｃ１ S(O)R ｂ１ , N.R. ｃ１ S (O) ２ R ｂ１ , N.R. ｃ１ S (O) ２ NR ｃ１ R ｄ１ , S(O)R ｂ１ , S(O)NR ｃ１ R ｄ１ , S(O) ２ R ｂ１ , S(O) ２ NR ｃ１ R ｄ１ , and B.R. ｈ１ R ｉ１ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ２ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ２ , S.R. ａ２ , C(O)R ｂ２ , C(O)NR ｃ２ R ｄ２ , C(O)OR ａ２ , O.C.(O.)R ｂ２ , OC(O)NR ｃ２ R ｄ２ , N.R. ｃ２ R ｄ２ , N.R. ｃ２ C(O)R ｂ２ , N.R. ｃ２ C(O)OR ａ２ , N.R. ｃ２ C(O)NR ｃ２ R ｄ２ , C(=NR ｅ２ ) R ｂ２ , C(=NOR ａ２ ) R ｂ２ , C(=NR ｅ２ ) NR ｃ２ R ｄ２ , N.R. ｃ２ C (=NR ｅ２ ) NR ｃ２ R ｄ２ , N.R. ｃ２ C (=NR ｅ２ ) R ｂ２ , N.R. ｃ２ S(O)R ｂ２ , N.R. ｃ２ S (O) ２ R ｂ２ , N.R. ｃ２ S (O) ２ NR ｃ２ R ｄ２ , S(O)R ｂ２ , S(O)NR ｃ２ R ｄ２ , S(O) ２ R ｂ２ , S(O) ２ NR ｃ２ R ｄ２ , and B.R. ｈ２ R ｉ２ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２３ substituted with 1, 2, 3, or 4 substituents independently selected from Cy １ is C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said 4- to 10-membered heterocycloalkyl and 5- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; ring-forming carbon atoms of the 5- to 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R １０ substituted with 1, 2, 3, or 4 substituents independently selected from R ４ teeth, 【Chemistry 3】 When is a single bond, it is selected from =O and =S; R ３ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ alkylene, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally represented by R ３０ substituted with 1, 2, 3, or 4 substituents independently selected from R ３ teeth, 【Chemistry 4】 is absent when is a double bond; R ４ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ３ , S.R. ａ３ , C(O)R ｂ３ , C(O)NR ｃ３ R ｄ３ , C(O)OR ａ３ , O.C.(O.)R ｂ３ , OC(O)NR ｃ３ R ｄ３ , N.R. ｃ３ R ｄ３ , N.R. ｃ３ C(O)R ｂ３ , N.R. ｃ３ C(O)OR ａ３ , N.R. ｃ３ C(O)NR ｃ３ R ｄ３ , C(=NR ｅ３ ) R ｂ３ , C(=NOR ａ３ ) R ｂ３ , C(=NR ｅ３ ) NR ｃ３ R ｄ３ , N.R. ｃ３ C (=NR ｅ３ ) NR ｃ３ R ｄ３ , N.R. ｃ３ C (=NR ｅ３ ) R ｂ３ , N.R. ｃ３ S(O)R ｂ３ , N.R. ｃ３ S (O) ２ R ｂ３ , N.R. ｃ３ S (O) ２ NR ｃ３ R ｄ３ , S(O)R ｂ３ , S(O)NR ｃ３ R ｄ３ , S(O) ２ R ｂ３ , S(O) ２ NR ｃ３ R ｄ３ , and B.R. ｈ３ R ｉ３ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３０ substituted with 1, 2, 3, or 4 substituents independently selected from R ５ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ５ , S.R. ａ５ , C(O)R ｂ５ , C(O)NR ｃ５ R ｄ５ , C(O)OR ａ５ , O.C.(O.)R ｂ５ , OC(O)NR ｃ５ R ｄ５ , N.R. ｃ５ R ｄ５ , N.R. ｃ５ C(O)R ｂ５ , N.R. ｃ５ C(O)OR ａ５ , N.R. ｃ５ C(O)NR ｃ５ R ｄ５ , C(=NR ｅ５ ) R ｂ５ , C(=NOR ａ５ ) R ｂ５ , C(=NR ｅ５ ) NR ｃ５ R ｄ５ , N.R. ｃ５ C (=NR ｅ５ ) NR ｃ５ R ｄ５ , N.R. ｃ５ C (=NR ｅ５ ) R ｂ５ , N.R. ｃ５ S(O)R ｂ５ , N.R. ｃ５ S (O) ２ R ｂ５ , N.R. ｃ５ S (O) ２ NR ｃ５ R ｄ５ , S(O)R ｂ５ , S(O)NR ｃ５ R ｄ５ , S(O) ２ R ｂ５ , S(O) ２ NR ｃ５ R ｄ５ , and B.R. ｈ５ R ｉ５ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ６ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ６ , S.R. ａ６ , C(O)R ｂ６ , C(O)NR ｃ６ R ｄ６ , C(O)OR ａ６ , O.C.(O.)R ｂ６ , OC(O)NR ｃ６ R ｄ６ , N.R. ｃ６ R ｄ６ , N.R. ｃ６ C(O)R ｂ６ , N.R. ｃ６ C(O)OR ａ６ , N.R. ｃ６ C(O)NR ｃ６ R ｄ６ , C(=NR ｅ６ ) R ｂ６ , C(=NOR ａ６ ) R ｂ６ , C(=NR ｅ６ ) NR ｃ６ R ｄ６ , N.R. ｃ６ C (=NR ｅ６ ) NR ｃ６ R ｄ６ , N.R. ｃ６ C (=NR ｅ６ ) R ｂ６ , N.R. ｃ６ S(O)R ｂ６ , N.R. ｃ６ S (O) ２ R ｂ６ , N.R. ｃ６ S (O) ２ NR ｃ６ R ｄ６ , S(O)R ｂ６ , S(O)NR ｃ６ R ｄ６ , S(O) ２ R ｂ６ , S(O) ２ NR ｃ６ R ｄ６ , and B.R. ｈ６ R ｉ６ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ６０ substituted with 1, 2, 3, or 4 substituents independently selected from R ７ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ７ , S.R. ａ７ , C(O)R ｂ７ , C(O)NR ｃ７ R ｄ７ , C(O)OR ａ７ , O.C.(O.)R ｂ７ , OC(O)NR ｃ７ R ｄ７ , N.R. ｃ７ R ｄ７ , N.R. ｃ７ C(O)R ｂ７ , N.R. ｃ７ C(O)OR ａ７ , N.R. ｃ７ C(O)NR ｃ７ R ｄ７ , C(=NR ｅ７ ) R ｂ７ , C(=NOR ａ７ ) R ｂ７ , C(=NR ｅ７ ) NR ｃ７ R ｄ７ , N.R. ｃ７ C (=NR ｅ７ ) NR ｃ７ R ｄ７ , N.R. ｃ７ C (=NR ｅ７ ) R ｂ７ , N.R. ｃ７ S(O)R ｂ７ , N.R. ｃ７ S (O) ２ R ｂ７ , N.R. ｃ７ S (O) ２ NR ｃ７ R ｄ７ , S(O)R ｂ７ , S(O)NR ｃ７ R ｄ７ , S(O) ２ R ｂ７ , S(O) ２ NR ｃ７ R ｄ７ , and B.R. ｈ７ R ｉ７ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ７０ substituted with 1, 2, 3, or 4 substituents independently selected from Cy ２ is C ３～１０ cycloalkyl, 4- to 14-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein the 4- to 14-membered heterocycloalkyl and the 5- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; and the ring-forming carbon atoms of the 5- to 10-membered heteroaryl and the 4- to 14-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 14-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２０ substituted with 1, 2, 3, or 4 substituents independently selected from Each R １０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ１０ , S.R. ａ１０ , C(O)R ｂ１０ , C(O)NR ｃ１０ R ｄ１０ , C(O)OR ａ１０ , O.C.(O.)R ｂ１０ , OC(O)NR ｃ１０ R ｄ１０ , N.R. ｃ１０ R ｄ１０ , N.R. ｃ１０ C(O)R ｂ１０ , N.R. ｃ１０ C(O)OR ａ１０ , N.R. ｃ１０ C(O)NR ｃ１０ R ｄ１０ , C(=NR ｅ１０ ) R ｂ１０ , C(=NOR ａ１０ ) R ｂ１０ , C(=NR ｅ１０ ) NR ｃ１０ R ｄ１０ , N.R. ｃ１０ C (=NR ｅ１０ ) NR ｃ１０ R ｄ１０ , N.R. ｃ１０ S(O)R ｂ１０ , N.R. ｃ１０ S (O) ２ R ｂ１０ , N.R. ｃ１０ S (O) ２ NR ｃ１０ R ｄ１０ , S(O)R ｂ１０ , S(O)NR ｃ１０ R ｄ１０ , S(O) ２ R ｂ１０ , S(O) ２ NR ｃ１０ R ｄ１０ , and B.R. ｈ１０ R ｉ１０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R １１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R １１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ１１ , S.R. ａ１１ , C(O)R ｂ１１ , C(O)NR ｃ１１ R ｄ１１ , C(O)OR ａ１１ , O.C.(O.)R ｂ１１ , OC(O)NR ｃ１１ R ｄ１１ , N.R. ｃ１１ R ｄ１１ , N.R. ｃ１１ C(O)R ｂ１１ , N.R. ｃ１１ C(O)OR ａ１１ , N.R. ｃ１１ C(O)NR ｃ１１ R ｄ１１ , N.R. ｃ１１ S(O)R ｂ１１ , N.R. ｃ１１ S (O) ２ R ｂ１１ , N.R. ｃ１１ S (O) ２ NR ｃ１１ R ｄ１１ , S(O)R ｂ１１ , S(O)NR ｃ１１ R ｄ１１ , S(O) ２ R ｂ１１ , S(O) ２ NR ｃ１１ R ｄ１１ , and B.R. ｈ１１ R ｉ１１ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R １２ substituted with 1, 2, 3, or 4 substituents independently selected from Each R １２ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocycloalkyl, halo, D, CN, OR ａ１２ , S.R. ａ１２ , C(O)R ｂ１２ , C(O)NR ｃ１２ R ｄ１２ , C(O)OR ａ１２ , O.C.(O.)R ｂ１２ , OC(O)NR ｃ１２ R ｄ１２ , N.R. ｃ１２ R ｄ１２ , N.R. ｃ１２ C(O)R ｂ１２ , N.R. ｃ１２ C(O)OR ａ１２ , N.R. ｃ１２ C(O)NR ｃ１２ R ｄ１２ , N.R. ｃ１２ S(O)R ｂ１２ , N.R. ｃ１２ S (O) ２ R ｂ１２ , N.R. ｃ１２ S (O) ２ NR ｃ１２ R ｄ１２ , S(O)R ｂ１２ , S(O)NR ｃ１２ R ｄ１２ , S(O) ２ R ｂ１２ , S(O) ２ NR ｃ１２ R ｄ１２ , and B.R. ｈ１２ R ｉ１２ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ２０ , S.R. ａ２０ , C(O)R ｂ２０ , C(O)NR ｃ２０ R ｄ２０ , C(O)OR ａ２０ , O.C.(O.)R ｂ２０ , OC(O)NR ｃ２０ R ｄ２０ , N.R. ｃ２０ R ｄ２０ , N.R. ｃ２０ C(O)R ｂ２０ , N.R. ｃ２０ C(O)OR ａ２０ , N.R. ｃ２０ C(O)NR ｃ２０ R ｄ２０ , C(=NR ｅ２０ ) R ｂ２０ , C(=NOR ａ２０ ) R ｂ２０ , C(=NR ｅ２０ ) NR ｃ２０ R ｄ２０ , N.R. ｃ２０ C (=NR ｅ２０ ) NR ｃ２０ R ｄ２０ , N.R. ｃ２０ S(O)R ｂ２０ , N.R. ｃ２０ S (O) ２ R ｂ２０ , N.R. ｃ２０ S (O) ２ NR ｃ２０ R ｄ２０ , S(O)R ｂ２０ , S(O)NR ｃ２０ R ｄ２０ , S(O) ２ R ｂ２０ , S(O) ２ NR ｃ２０ R ｄ２０ , and B.R. ｈ２０ R ｉ２０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ２１ , S.R. ａ２１ , C(O)R ｂ２１ , C(O)NR ｃ２１ R ｄ２１ , C(O)OR ａ２１ , O.C.(O.)R ｂ２１ , OC(O)NR ｃ２１ R ｄ２１ , N.R. ｃ２１ R ｄ２１ , N.R. ｃ２１ C(O)R ｂ２１ , N.R. ｃ２１ C(O)OR ａ２１ , N.R. ｃ２１ C(O)NR ｃ２１ R ｄ２１ , N.R. ｃ２１ S(O)R ｂ２１ , N.R. ｃ２１ S (O) ２ R ｂ２１ , N.R. ｃ２１ S (O) ２ NR ｃ２１ R ｄ２１ , S(O)R ｂ２１ , S(O)NR ｃ２１ R ｄ２１ , S(O) ２ R ｂ２１ , S(O) ２ NR ｃ２１ R ｄ２１ , and B.R. ｈ２１ R ｉ２１ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２２ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２２ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocycloalkyl, halo, D, CN, OR ａ２２ , S.R. ａ２２ , C(O)R ｂ２２ , C(O)NR ｃ２２ R ｄ２２ , C(O)OR ａ２２ , O.C.(O.)R ｂ２２ , OC(O)NR ｃ２２ R ｄ２２ , N.R. ｃ２２ R ｄ２２ , N.R. ｃ２２ C(O)R ｂ２２ , N.R. ｃ２２ C(O)OR ａ２２ , N.R. ｃ２２ C(O)NR ｃ２２ R ｄ２２ , N.R. ｃ２２ S(O)R ｂ２２ , N.R. ｃ２２ S (O) ２ R ｂ２２ , N.R. ｃ２２ S (O) ２ NR ｃ２２ R ｄ２２ , S(O)R ｂ２２ , S(O)NR ｃ２２ R ｄ２２ , S(O) ２ R ｂ２２ , S(O) ２ NR ｃ２２ R ｄ２２ , and B.R. ｈ２２ R ｉ２２ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２３ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ２３ , S.R. ａ２３ , C(O)R ｂ２３ , C(O)NR ｃ２３ R ｄ２３ , C(O)OR ａ２３ , O.C.(O.)R ｂ２３ , OC(O)NR ｃ２３ R ｄ２３ , N.R. ｃ２３ R ｄ２３ , N.R. ｃ２３ C(O)R ｂ２３ , N.R. ｃ２３ C(O)OR ａ２３ , N.R. ｃ２３ C(O)NR ｃ２３ R ｄ２３ , N.R. ｃ２３ S(O)R ｂ２３ , N.R. ｃ２３ S (O) ２ R ｂ２３ , N.R. ｃ２３ S (O) ２ NR ｃ２３ R ｄ２３ , S(O)R ｂ２３ , S(O)NR ｃ２３ R ｄ２３ , S(O) ２ R ｂ２３ , S(O) ２ NR ｃ２３ R ｄ２３ , and B.R. ｈ２３ R ｉ２３ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２４ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２４ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocycloalkyl, halo, D, CN, OR ａ２４ , S.R. ａ２４ , C(O)R ｂ２４ , C(O)NR ｃ２４ R ｄ２４ , C(O)OR ａ２４ , O.C.(O.)R ｂ２４ , OC(O)NR ｃ２４ R ｄ２４ , N.R. ｃ２４ R ｄ２４ , N.R. ｃ２４ C(O)R ｂ２４ , N.R. ｃ２４ C(O)OR ａ２４ , N.R. ｃ２４ C(O)NR ｃ２４ R ｄ２４ , N.R. ｃ２４ S(O)R ｂ２４ , N.R. ｃ２４ S (O) ２ R ｂ２４ , N.R. ｃ２４ S (O) ２ NR ｃ２４ R ｄ２４ , S(O)R ｂ２４ , S(O)NR ｃ２４ R ｄ２４ , S(O) ２ R ｂ２４ , S(O) ２ NR ｃ２４ R ｄ２４ , and B.R. ｈ２４ R ｉ２４ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ３０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ３０ , S.R. ａ３０ , C(O)R ｂ３０ , C(O)NR ｃ３０ R ｄ３０ , C(O)OR ａ３０ , O.C.(O.)R ｂ３０ , OC(O)NR ｃ３０ R ｄ３０ , N.R. ｃ３０ R ｄ３０ , N.R. ｃ３０ C(O)R ｂ３０ , N.R. ｃ３０ C(O)OR ａ３０ , N.R. ｃ３０ C(O)NR ｃ３０ R ｄ３０ , N.R. ｃ３０ S(O)R ｂ３０ , N.R. ｃ３０ S (O) ２ R ｂ３０ , N.R. ｃ３０ S (O) ２ NR ｃ３０ R ｄ３０ , S(O)R ｂ３０ , S(O)NR ｃ３０ R ｄ３０ , S(O) ２ R ｂ３０ , S(O) ２ NR ｃ３０ R ｄ３０ , and B.R. ｈ３０ R ｉ３０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ３１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ３１ , S.R. ａ３１ , C(O)R ｂ３１ , C(O)NR ｃ３１ R ｄ３１ , C(O)OR ａ３１ , O.C.(O.)R ｂ３１ , OC(O)NR ｃ３１ R ｄ３１ , N.R. ｃ３１ R ｄ３１ , N.R. ｃ３１ C(O)R ｂ３１ , N.R. ｃ３１ C(O)OR ａ３１ , N.R. ｃ３１ C(O)NR ｃ３１ R ｄ３１ , N.R. ｃ３１ S(O)R ｂ３１ , N.R. ｃ３１ S (O) ２ R ｂ３１ , N.R. ｃ３１ S (O) ２ NR ｃ３１ R ｄ３１ , S(O)R ｂ３１ , S(O)NR ｃ３１ R ｄ３１ , S(O) ２ R ｂ３１ , S(O) ２ NR ｃ３１ R ｄ３１ , and B.R. ｈ３１ R ｉ３１ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３２ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ３２ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocycloalkyl, halo, D, CN, OR ａ３２ , S.R. ａ３２ , C(O)R ｂ３２ , C(O)NR ｃ３２ R ｄ３２ , C(O)OR ａ３２ , O.C.(O.)R ｂ３２ , OC(O)NR ｃ３２ R ｄ３２ , N.R. ｃ３２ R ｄ３２ , N.R. ｃ３２ C(O)R ｂ３２ , N.R. ｃ３２ C(O)OR ａ３２ , N.R. ｃ３２ C(O)NR ｃ３２ R ｄ３２ , N.R. ｃ３２ S(O)R ｂ３２ , N.R. ｃ３２ S (O) ２ R ｂ３２ , N.R. ｃ３２ S (O) ２ NR ｃ３２ R ｄ３２ , S(O)R ｂ３２ , S(O)NR ｃ３２ R ｄ３２ , S(O) ２ R ｂ３２ , S(O) ２ NR ｃ３２ R ｄ３２ , and B.R. ｈ３２ R ｉ３２ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ６０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ６０ , S.R. ａ６０ , C(O)R ｂ６０ , C(O)NR ｃ６０ R ｄ６０ , C(O)OR ａ６０ , O.C.(O.)R ｂ６０ , OC(O)NR ｃ６０ R ｄ６０ , N.R. ｃ６０ R ｄ６０ , N.R. ｃ６０ C(O)R ｂ６０ , N.R. ｃ６０ C(O)OR ａ６０ , N.R. ｃ６０ C(O)NR ｃ６０ R ｄ６０ , N.R. ｃ６０ S(O)R ｂ６０ , N.R. ｃ６０ S (O) ２ R ｂ６０ , N.R. ｃ６０ S (O) ２ NR ｃ６０ R ｄ６０ , S(O)R ｂ６０ , S(O)NR ｃ６０ R ｄ６０ , S(O) ２ R ｂ６０ , S(O) ２ NR ｃ６０ R ｄ６０ , and B.R. ｈ６０ R ｉ６０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ６１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ６１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ６１ , S.R. ａ６１ , C(O)R ｂ６１ , C(O)NR ｃ６１ R ｄ６１ , C(O)OR ａ６１ , O.C.(O.)R ｂ６１ , OC(O)NR ｃ６１ R ｄ６１ , N.R. ｃ６１ R ｄ６１ , N.R. ｃ６１ C(O)R ｂ６１ , N.R. ｃ６１ C(O)OR ａ６１ , N.R. ｃ６１ C(O)NR ｃ６１ R ｄ６１ , N.R. ｃ６１ S(O)R ｂ６１ , N.R. ｃ６１ S (O) ２ R ｂ６１ , N.R. ｃ６１ S (O) ２ NR ｃ６１ R ｄ６１ , S(O)R ｂ６１ , S(O)NR ｃ６１ R ｄ６１ , S(O) ２ R ｂ６１ , S(O) ２ NR ｃ６１ R ｄ６１ , and B.R. ｈ６１ R ｉ６１ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ６２ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ６２ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocycloalkyl, halo, D, CN, OR ａ６２ , S.R. ａ６２ , C(O)R ｂ６２ , C(O)NR ｃ６２ R ｄ６２ , C(O)OR ａ６２ , O.C.(O.)R ｂ６２ , OC(O)NR ｃ６２ R ｄ６２ , N.R. ｃ６２ R ｄ６２ , N.R. ｃ６２ C(O)R ｂ６２ , N.R. ｃ６２ C(O)OR ａ６２ , N.R. ｃ６２ C(O)NR ｃ６２ R ｄ６２ , N.R. ｃ６２ S(O)R ｂ６２ , N.R. ｃ６２ S (O) ２ R ｂ６２ , N.R. ｃ６２ S (O) ２ NR ｃ６２ R ｄ６２ , S(O)R ｂ６２ , S(O)NR ｃ６２ R ｄ６２ , S(O) ２ R ｂ６２ , S(O) ２ NR ｃ６２ R ｄ６２ , and B.R. ｈ６２ R ｉ６２ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ７０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ７０ , S.R. ａ７０ , C(O)R ｂ７０ , C(O)NR ｃ７０ R ｄ７０ , C(O)OR ａ７０ , O.C.(O.)R ｂ７０ , OC(O)NR ｃ７０ R ｄ７０ , N.R. ｃ７０ R ｄ７０ , N.R. ｃ７０ C(O)R ｂ７０ , N.R. ｃ７０ C(O)OR ａ７０ , N.R. ｃ７０ C(O)NR ｃ７０ R ｄ７０ , N.R. ｃ７０ S(O)R ｂ７０ , N.R. ｃ７０ S (O) ２ R ｂ７０ , N.R. ｃ７０ S (O) ２ NR ｃ７０ R ｄ７０ , S(O)R ｂ７０ , S(O)NR ｃ７０ R ｄ７０ , S(O) ２ R ｂ７０ , S(O) ２ NR ｃ７０ R ｄ７０ , and B.R. ｈ７０ R ｉ７０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ａ１ , R ｂ１ , R ｃ１ , and R ｄ１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ｇ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ１ and R ｄ１ together with the N atom to which they are attached, form R ｇ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ１ and R ｉ１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ１ and R ｉ１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２ , R ｂ２ , R ｃ２ , and R ｄ２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２３ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２ and R ｄ２ together with the N atom to which they are attached, form R ２３ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ２ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ２ and R ｉ２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２ and R ｉ２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３ , R ｂ３ , R ｃ３ , and R ｄ３ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ３０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３ and R ｄ３ together with the N atom to which they are attached, form R ３０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ３ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ３ and R ｉ３ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３ and R ｉ３ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ５ , R ｂ５ , R ｃ５ , and R ｄ５ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ｇ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ５ and R ｄ５ together with the N atom to which they are attached, form R ｇ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R ｅ５ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ５ and R ｉ５ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ５ and R ｉ５ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ６ , R ｂ６ , R ｃ６ , and R ｄ６ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ６０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ６ and R ｄ６ together with the N atom to which they are attached, form R ６０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R ｅ６ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ６ and R ｉ６ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ６ and R ｉ６ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ７ , R ｂ７ , R ｃ７ , and R ｄ７ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ７０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ７ and R ｄ７ together with the N atom to which they are attached, form R ７０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ７ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ７ and R ｉ７ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ７ and R ｉ７ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ１０ , R ｂ１０ , R ｃ１０ , and R ｄ１０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R １１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ１０ and R ｄ１０ together with the N atom to which they are attached, form R １１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ１０ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ１０ and R ｉ１０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ１０ and R ｉ１０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ１１ , R ｂ１１ , R ｃ１１ , and R ｄ１１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R １２ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ１１ and R ｄ１１ together with the N atom to which they are attached, form R １２ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ１１ and R ｉ１１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ１１ and R ｉ１１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ１２ , R ｂ１２ , R ｃ１２ , and R ｄ１２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ haloalkyl; １～６ Alkyl, C ２～６ Alkenyl, and C ２～６ Each alkynyl is optionally selected from R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ｈ１２ and R ｉ１２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ１２ and R ｉ１２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２０ , R ｂ２０ , R ｃ２０ , and R ｄ２０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２０ and R ｄ２０ together with the N atom to which they are attached, form R ２１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ２０ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ２０ and R ｉ２０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２０ and R ｉ２０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２１ , R ｂ２１ , R ｃ２１ , and R ｄ２１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ２２ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２１ and R ｄ２１ together with the N atom to which they are attached, form R ２２ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ２１ and R ｉ２１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２１ and R ｉ２１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２２ , R ｂ２２ , R ｃ２２ , and R ｄ２２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ haloalkyl; １～６ Alkyl, C ２～６ Alkenyl, and C ２～６ Each alkynyl is optionally selected from R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ｈ２２ and R ｉ２２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２２ and R ｉ２２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２３ , R ｂ２３ , R ｃ２３ , and R ｄ２３ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ２４ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２３ and R ｄ２３ together with the N atom to which they are attached, form R ２４ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ２３ and R ｉ２３ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２３ and R ｉ２３ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２４ , R ｂ２４ , R ｃ２４ , and R ｄ２４ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ haloalkyl; １～６ Alkyl, C ２～６ Alkenyl, and C ２～６ Each alkynyl is optionally selected from R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ｈ２４ and R ｉ２４ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２４ and R ｉ２４ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３０ , R ｂ３０ , R ｃ３０ , and R ｄ３０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ３１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３０ and R ｄ３０ together with the N atom to which they are attached, form R ３１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ｈ３０ and R ｉ３０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３０ and R ｉ３０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３１ , R ｂ３１ , R ｃ３１ , and R ｄ３１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ３２ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３１ and R ｄ３１ together with the N atom to which they are attached, form R ３２ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ３１ and R ｉ３１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３１ and R ｉ３１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３２ , R ｂ３２ , R ｃ３２ , and R ｄ３２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ haloalkyl; １～６ Alkyl, C ２～６ Alkenyl, and C ２～６ Each alkynyl is optionally selected from R ｇ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３２ and R ｄ３２ together with the N atom to which they are attached, form R ｇ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ｈ３２ and R ｉ３２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３２ and R ｉ３２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ６０ , R ｂ６０ , R ｃ６０ , and R ｄ６０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ６１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ６０ and R ｄ６０ together with the N atom to which they are attached, form R ６１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ｈ６０ and R ｉ６０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ６０ and R ｉ６０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ６１ , R ｂ６１ , R ｃ６１ , and R ｄ６１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ６２ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ６１ and R ｄ６１ together with the N atom to which they are attached, form R ６２ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ６１ and R ｉ６１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ６１ and R ｉ６１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ６２ , R ｂ６２ , R ｃ６２ , and R ｄ６２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ haloalkyl; １～６ Alkyl, C ２～６ Alkenyl, and C ２～６ Each alkynyl is optionally selected from R ｇ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ６２ and R ｄ６２ together with the N atom to which they are attached, form R ｇ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ｈ６２ and R ｉ６２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ６２ and R ｉ６２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ７０ , R ｂ７０ , R ｃ７０ , and R ｄ７０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ｇ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ７０ and R ｄ７０ together with the N atom to which they are attached, form R ｇ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ｈ７０ and R ｉ７０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ７０ and R ｉ７０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; Each R ｇ D, OH, NO ２ , CN, Halo, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ Cycloalkyl, C ３～６ Cycloalkyl-C １～２ Alkylene, C １～６ Alkoxy, C １～６ Haloalkoxy, C １～３ Alkoxy-C １～３ Alkyl, C １～３ Alkoxy-C １～３ Alkoxy, HO-C １～３ Alkoxy, HO-C １～３ Alkyl, cyano-C １～３ Alkyl, H ２ N-C １～３ Alkyl, amino, C １～６ Alkylamino, di(C １～６ alkyl) amino, thio, C １～６ Alkylthio, C １～６ Alkylsulfinyl, C １～６ Alkyl sulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, carboxy, C １～６ Alkylcarbonyl, C １～６ Alkoxycarbonyl, C １～６ Alkylcarbonylamino, C １～６ Alkoxycarbonylamino, C １～６ Alkylcarbonyloxy, aminocarbonyloxy, C １～６ Alkylaminocarbonyloxy, di(C １～６ alkyl)aminocarbonyloxy, C １～６ Alkyl sulfonyl amino, amino sulfonyl, C １～６ Alkylaminosulfonyl, di(C １～６ alkyl)aminosulfonyl, aminosulfonylamino, C １～６ Alkylaminosulfonylamino, di(C １～６ alkyl)aminosulfonylamino, aminocarbonylamino, C １～６ Alkylaminocarbonylamino, and di(C １～６ independently selected from: (alkyl)aminocarbonylamino; however, (a) Cy １ is other than 3,5-dimethylisoxazol-4-yl; (b) R ３ is CH ２ CF ３ other than). 【Request 2】 【Chemical 5】 represents a single or double bond; -AR １ =BR ２ - is -N=CR ２ - and - CR １ =N-; X is N and CR ５ Selected from: Y is N and CR ６ Selected from: R １ H, D, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5-10 membered heteroaryl, halo, CN, OR ａ１ , S.R. ａ１ , C(O)R ｂ１ , C(O)NR ｃ１ R ｄ１ , C(O)OR ａ１ , O.C.(O.)R ｂ１ , OC(O)NR ｃ１ R ｄ１ , N.R. ｃ１ R ｄ１ , N.R. ｃ１ C(O)R ｂ１ , N.R. ｃ１ C(O)OR ａ１ , N.R. ｃ１ C(O)NR ｃ１ R ｄ１ , N.R. ｃ１ S(O)R ｂ１ , N.R. ｃ１ S (O) ２ R ｂ１ , N.R. ｃ１ S (O) ２ NR ｃ１ R ｄ１ , S(O)R ｂ１ , S(O)NR ｃ１ R ｄ１ , S(O) ２ R ｂ１ , S(O) ２ NR ｃ１ R ｄ１ , and B.R. ｈ１ R ｉ１ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ２ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ２ , S.R. ａ２ , C(O)R ｂ２ , C(O)NR ｃ２ R ｄ２ , C(O)OR ａ２ , O.C.(O.)R ｂ２ , OC(O)NR ｃ２ R ｄ２ , N.R. ｃ２ R ｄ２ , N.R. ｃ２ C(O)R ｂ２ , N.R. ｃ２ C(O)OR ａ２ , N.R. ｃ２ C(O)NR ｃ２ R ｄ２ , C(=NR ｅ２ ) R ｂ２ , C(=NOR ａ２ ) R ｂ２ , C(=NR ｅ２ ) NR ｃ２ R ｄ２ , N.R. ｃ２ C (=NR ｅ２ ) NR ｃ２ R ｄ２ , N.R. ｃ２ C (=NR ｅ２ ) R ｂ２ , N.R. ｃ２ S(O)R ｂ２ , N.R. ｃ２ S (O) ２ R ｂ２ , N.R. ｃ２ S (O) ２ NR ｃ２ R ｄ２ , S(O)R ｂ２ , S(O)NR ｃ２ R ｄ２ , S(O) ２ R ｂ２ , S(O) ２ NR ｃ２ R ｄ２ , and B.R. ｈ２ R ｉ２ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２３ substituted with 1, 2, 3, or 4 substituents independently selected from Cy １ is C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 6- to 10-membered heteroaryl, wherein said 4- to 10-membered heterocycloalkyl and 6- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; ring-forming carbon atoms of the 6- to 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 6- to 10-membered heteroaryl are each optionally represented by R １０ substituted with 1, 2, 3, or 4 substituents independently selected from R ４ teeth, 【Chemistry 6】 When is a single bond, it is selected from =O and =S; R ３ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ alkylene, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally represented by R ３０ substituted with 1, 2, 3, or 4 substituents independently selected from R ３ teeth, 【Chemistry 7】 is absent when is a double bond; R ４ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ３ , S.R. ａ３ , C(O)R ｂ３ , C(O)NR ｃ３ R ｄ３ , C(O)OR ａ３ , O.C.(O.)R ｂ３ , OC(O)NR ｃ３ R ｄ３ , N.R. ｃ３ R ｄ３ , N.R. ｃ３ C(O)R ｂ３ , N.R. ｃ３ C(O)OR ａ３ , N.R. ｃ３ C(O)NR ｃ３ R ｄ３ , C(=NR ｅ３ ) R ｂ３ , C(=NOR ａ３ ) R ｂ３ , C(=NR ｅ３ ) NR ｃ３ R ｄ３ , N.R. ｃ３ C (=NR ｅ３ ) NR ｃ３ R ｄ３ , N.R. ｃ３ C (=NR ｅ３ ) R ｂ３ , N.R. ｃ３ S(O)R ｂ３ , N.R. ｃ３ S (O) ２ R ｂ３ , N.R. ｃ３ S (O) ２ NR ｃ３ R ｄ３ , S(O)R ｂ３ , S(O)NR ｃ３ R ｄ３ , S(O) ２ R ｂ３ , S(O) ２ NR ｃ３ R ｄ３ , and B.R. ｈ３ R ｉ３ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３０ substituted with 1, 2, 3, or 4 substituents independently selected from R ５ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ５ , S.R. ａ５ , C(O)R ｂ５ , C(O)NR ｃ５ R ｄ５ , C(O)OR ａ５ , O.C.(O.)R ｂ５ , OC(O)NR ｃ５ R ｄ５ , N.R. ｃ５ R ｄ５ , N.R. ｃ５ C(O)R ｂ５ , N.R. ｃ５ C(O)OR ａ５ , N.R. ｃ５ C(O)NR ｃ５ R ｄ５ , C(=NR ｅ５ ) R ｂ５ , C(=NOR ａ５ ) R ｂ５ , C(=NR ｅ５ ) NR ｃ５ R ｄ５ , N.R. ｃ５ C (=NR ｅ５ ) NR ｃ５ R ｄ５ , N.R. ｃ５ C (=NR ｅ５ ) R ｂ５ , N.R. ｃ５ S(O)R ｂ５ , N.R. ｃ５ S (O) ２ R ｂ５ , N.R. ｃ５ S (O) ２ NR ｃ５ R ｄ５ , S(O)R ｂ５ , S(O)NR ｃ５ R ｄ５ , S(O) ２ R ｂ５ , S(O) ２ NR ｃ５ R ｄ５ , and B.R. ｈ５ R ｉ５ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ｇ substituted with 1, 2, 3, or 4 substituents independently selected from R ６ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ６ , S.R. ａ６ , C(O)R ｂ６ , C(O)NR ｃ６ R ｄ６ , C(O)OR ａ６ , O.C.(O.)R ｂ６ , OC(O)NR ｃ６ R ｄ６ , N.R. ｃ６ R ｄ６ , N.R. ｃ６ C(O)R ｂ６ , N.R. ｃ６ C(O)OR ａ６ , N.R. ｃ６ C(O)NR ｃ６ R ｄ６ , C(=NR ｅ６ ) R ｂ６ , C(=NOR ａ６ ) R ｂ６ , C(=NR ｅ６ ) NR ｃ６ R ｄ６ , N.R. ｃ６ C (=NR ｅ６ ) NR ｃ６ R ｄ６ , N.R. ｃ６ C (=NR ｅ６ ) R ｂ６ , N.R. ｃ６ S(O)R ｂ６ , N.R. ｃ６ S (O) ２ R ｂ６ , N.R. ｃ６ S (O) ２ NR ｃ６ R ｄ６ , S(O)R ｂ６ , S(O)NR ｃ６ R ｄ６ , S(O) ２ R ｂ６ , S(O) ２ NR ｃ６ R ｄ６ , and B.R. ｈ６ R ｉ６ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ６０ substituted with 1, 2, 3, or 4 substituents independently selected from R ７ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ７ , S.R. ａ７ , C(O)R ｂ７ , C(O)NR ｃ７ R ｄ７ , C(O)OR ａ７ , O.C.(O.)R ｂ７ , OC(O)NR ｃ７ R ｄ７ , N.R. ｃ７ R ｄ７ , N.R. ｃ７ C(O)R ｂ７ , N.R. ｃ７ C(O)OR ａ７ , N.R. ｃ７ C(O)NR ｃ７ R ｄ７ , C(=NR ｅ７ ) R ｂ７ , C(=NOR ａ７ ) R ｂ７ , C(=NR ｅ７ ) NR ｃ７ R ｄ７ , N.R. ｃ７ C (=NR ｅ７ ) NR ｃ７ R ｄ７ , N.R. ｃ７ C (=NR ｅ７ ) R ｂ７ , N.R. ｃ７ S(O)R ｂ７ , N.R. ｃ７ S (O) ２ R ｂ７ , N.R. ｃ７ S (O) ２ NR ｃ７ R ｄ７ , S(O)R ｂ７ , S(O)NR ｃ７ R ｄ７ , S(O) ２ R ｂ７ , S(O) ２ NR ｃ７ R ｄ７ , and B.R. ｈ７ R ｉ７ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ７０ substituted with 1, 2, 3, or 4 substituents independently selected from Cy ２ is C ３～１０ cycloalkyl, 4- to 14-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein the 4- to 14-membered heterocycloalkyl and the 5- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; and the ring-forming carbon atoms of the 5- to 10-membered heteroaryl and the 4- to 14-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 14-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２０ substituted with 1, 2, 3, or 4 substituents independently selected from Each R １０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ１０ , S.R. ａ１０ , C(O)R ｂ１０ , C(O)NR ｃ１０ R ｄ１０ , C(O)OR ａ１０ , O.C.(O.)R ｂ１０ , OC(O)NR ｃ１０ R ｄ１０ , N.R. ｃ１０ R ｄ１０ , N.R. ｃ１０ C(O)R ｂ１０ , N.R. ｃ１０ C(O)OR ａ１０ , N.R. ｃ１０ C(O)NR ｃ１０ R ｄ１０ , C(=NR ｅ１０ ) R ｂ１０ , C(=NOR ａ１０ ) R ｂ１０ , C(=NR ｅ１０ ) NR ｃ１０ R ｄ１０ , N.R. ｃ１０ C (=NR ｅ１０ ) NR ｃ１０ R ｄ１０ , N.R. ｃ１０ S(O)R ｂ１０ , N.R. ｃ１０ S (O) ２ R ｂ１０ , N.R. ｃ１０ S (O) ２ NR ｃ１０ R ｄ１０ , S(O)R ｂ１０ , S(O)NR ｃ１０ R ｄ１０ , S(O) ２ R ｂ１０ , S(O) ２ NR ｃ１０ R ｄ１０ , and B.R. ｈ１０ R ｉ１０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R １１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R １１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ１１ , S.R. ａ１１ , C(O)R ｂ１１ , C(O)NR ｃ１１ R ｄ１１ , C(O)OR ａ１１ , O.C.(O.)R ｂ１１ , OC(O)NR ｃ１１ R ｄ１１ , N.R. ｃ１１ R ｄ１１ , N.R. ｃ１１ C(O)R ｂ１１ , N.R. ｃ１１ C(O)OR ａ１１ , N.R. ｃ１１ C(O)NR ｃ１１ R ｄ１１ , N.R. ｃ１１ S(O)R ｂ１１ , N.R. ｃ１１ S (O) ２ R ｂ１１ , N.R. ｃ１１ S (O) ２ NR ｃ１１ R ｄ１１ , S(O)R ｂ１１ , S(O)NR ｃ１１ R ｄ１１ , S(O) ２ R ｂ１１ , S(O) ２ NR ｃ１１ R ｄ１１ , and B.R. ｈ１１ R ｉ１１ are independently selected from Each R ２０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ２０ , S.R. ａ２０ , C(O)R ｂ２０ , C(O)NR ｃ２０ R ｄ２０ , C(O)OR ａ２０ , O.C.(O.)R ｂ２０ , OC(O)NR ｃ２０ R ｄ２０ , N.R. ｃ２０ R ｄ２０ , N.R. ｃ２０ C(O)R ｂ２０ , N.R. ｃ２０ C(O)OR ａ２０ , N.R. ｃ２０ C(O)NR ｃ２０ R ｄ２０ , C(=NR ｅ２０ ) R ｂ２０ , C(=NOR ａ２０ ) R ｂ２０ , C(=NR ｅ２０ ) NR ｃ２０ R ｄ２０ , N.R. ｃ２０ C (=NR ｅ２０ ) NR ｃ２０ R ｄ２０ , N.R. ｃ２０ S(O)R ｂ２０ , N.R. ｃ２０ S (O) ２ R ｂ２０ , N.R. ｃ２０ S (O) ２ NR ｃ２０ R ｄ２０ , S(O)R ｂ２０ , S(O)NR ｃ２０ R ｄ２０ , S(O) ２ R ｂ２０ , S(O) ２ NR ｃ２０ R ｄ２０ , and B.R. ｈ２０ R ｉ２０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ２１ , S.R. ａ２１ , C(O)R ｂ２１ , C(O)NR ｃ２１ R ｄ２１ , C(O)OR ａ２１ , O.C.(O.)R ｂ２１ , OC(O)NR ｃ２１ R ｄ２１ , N.R. ｃ２１ R ｄ２１ , N.R. ｃ２１ C(O)R ｂ２１ , N.R. ｃ２１ C(O)OR ａ２１ , N.R. ｃ２１ C(O)NR ｃ２１ R ｄ２１ , N.R. ｃ２１ S(O)R ｂ２１ , N.R. ｃ２１ S (O) ２ R ｂ２１ , N.R. ｃ２１ S (O) ２ NR ｃ２１ R ｄ２１ , S(O)R ｂ２１ , S(O)NR ｃ２１ R ｄ２１ , S(O) ２ R ｂ２１ , S(O) ２ NR ｃ２１ R ｄ２１ , and B.R. ｈ２１ R ｉ２１ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２２ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２２ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocycloalkyl, halo, D, CN, OR ａ２２ , S.R. ａ２２ , C(O)R ｂ２２ , C(O)NR ｃ２２ R ｄ２２ , C(O)OR ａ２２ , O.C.(O.)R ｂ２２ , OC(O)NR ｃ２２ R ｄ２２ , N.R. ｃ２２ R ｄ２２ , N.R. ｃ２２ C(O)R ｂ２２ , N.R. ｃ２２ C(O)OR ａ２２ , N.R. ｃ２２ C(O)NR ｃ２２ R ｄ２２ , N.R. ｃ２２ S(O)R ｂ２２ , N.R. ｃ２２ S (O) ２ R ｂ２２ , N.R. ｃ２２ S (O) ２ NR ｃ２２ R ｄ２２ , S(O)R ｂ２２ , S(O)NR ｃ２２ R ｄ２２ , S(O) ２ R ｂ２２ , S(O) ２ NR ｃ２２ R ｄ２２ , and B.R. ｈ２２ R ｉ２２ are independently selected from Each R ２３ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ２３ , S.R. ａ２３ , C(O)R ｂ２３ , C(O)NR ｃ２３ R ｄ２３ , C(O)OR ａ２３ , O.C.(O.)R ｂ２３ , OC(O)NR ｃ２３ R ｄ２３ , N.R. ｃ２３ R ｄ２３ , N.R. ｃ２３ C(O)R ｂ２３ , N.R. ｃ２３ C(O)OR ａ２３ , N.R. ｃ２３ C(O)NR ｃ２３ R ｄ２３ , N.R. ｃ２３ S(O)R ｂ２３ , N.R. ｃ２３ S (O) ２ R ｂ２３ , N.R. ｃ２３ S (O) ２ NR ｃ２３ R ｄ２３ , S(O)R ｂ２３ , S(O)NR ｃ２３ R ｄ２３ , S(O) ２ R ｂ２３ , S(O) ２ NR ｃ２３ R ｄ２３ , and B.R. ｈ２３ R ｉ２３ are independently selected from Each R ３０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ３０ , S.R. ａ３０ , C(O)R ｂ３０ , C(O)NR ｃ３０ R ｄ３０ , C(O)OR ａ３０ , O.C.(O.)R ｂ３０ , OC(O)NR ｃ３０ R ｄ３０ , N.R. ｃ３０ R ｄ３０ , N.R. ｃ３０ C(O)R ｂ３０ , N.R. ｃ３０ C(O)OR ａ３０ , N.R. ｃ３０ C(O)NR ｃ３０ R ｄ３０ , N.R. ｃ３０ S(O)R ｂ３０ , N.R. ｃ３０ S (O) ２ R ｂ３０ , N.R. ｃ３０ S (O) ２ NR ｃ３０ R ｄ３０ , S(O)R ｂ３０ , S(O)NR ｃ３０ R ｄ３０ , S(O) ２ R ｂ３０ , S(O) ２ NR ｃ３０ R ｄ３０ , and B.R. ｈ３０ R ｉ３０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ３１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ３１ , S.R. ａ３１ , C(O)R ｂ３１ , C(O)NR ｃ３１ R ｄ３１ , C(O)OR ａ３１ , O.C.(O.)R ｂ３１ , OC(O)NR ｃ３１ R ｄ３１ , N.R. ｃ３１ R ｄ３１ , N.R. ｃ３１ C(O)R ｂ３１ , N.R. ｃ３１ C(O)OR ａ３１ , N.R. ｃ３１ C(O)NR ｃ３１ R ｄ３１ , N.R. ｃ３１ S(O)R ｂ３１ , N.R. ｃ３１ S (O) ２ R ｂ３１ , N.R. ｃ３１ S (O) ２ NR ｃ３１ R ｄ３１ , S(O)R ｂ３１ , S(O)NR ｃ３１ R ｄ３１ , S(O) ２ R ｂ３１ , S(O) ２ NR ｃ３１ R ｄ３１ , and B.R. ｈ３１ R ｉ３１ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３２ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ３２ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocycloalkyl, halo, D, CN, OR ａ３２ , S.R. ａ３２ , C(O)R ｂ３２ , C(O)NR ｃ３２ R ｄ３２ , C(O)OR ａ３２ , O.C.(O.)R ｂ３２ , OC(O)NR ｃ３２ R ｄ３２ , N.R. ｃ３２ R ｄ３２ , N.R. ｃ３２ C(O)R ｂ３２ , N.R. ｃ３２ C(O)OR ａ３２ , N.R. ｃ３２ C(O)NR ｃ３２ R ｄ３２ , N.R. ｃ３２ S(O)R ｂ３２ , N.R. ｃ３２ S (O) ２ R ｂ３２ , N.R. ｃ３２ S (O) ２ NR ｃ３２ R ｄ３２ , S(O)R ｂ３２ , S(O)NR ｃ３２ R ｄ３２ , S(O) ２ R ｂ３２ , S(O) ２ NR ｃ３２ R ｄ３２ , and B.R. ｈ３２ R ｉ３２ are independently selected from Each R ６０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ６０ , S.R. ａ６０ , C(O)R ｂ６０ , C(O)NR ｃ６０ R ｄ６０ , C(O)OR ａ６０ , O.C.(O.)R ｂ６０ , OC(O)NR ｃ６０ R ｄ６０ , N.R. ｃ６０ R ｄ６０ , N.R. ｃ６０ C(O)R ｂ６０ , N.R. ｃ６０ C(O)OR ａ６０ , N.R. ｃ６０ C(O)NR ｃ６０ R ｄ６０ , N.R. ｃ６０ S(O)R ｂ６０ , N.R. ｃ６０ S (O) ２ R ｂ６０ , N.R. ｃ６０ S (O) ２ NR ｃ６０ R ｄ６０ , S(O)R ｂ６０ , S(O)NR ｃ６０ R ｄ６０ , S(O) ２ R ｂ６０ , S(O) ２ NR ｃ６０ R ｄ６０ , and B.R. ｈ６０ R ｉ６０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ６１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ６１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ６１ , S.R. ａ６１ , C(O)R ｂ６１ , C(O)NR ｃ６１ R ｄ６１ , C(O)OR ａ６１ , O.C.(O.)R ｂ６１ , OC(O)NR ｃ６１ R ｄ６１ , N.R. ｃ６１ R ｄ６１ , N.R. ｃ６１ C(O)R ｂ６１ , N.R. ｃ６１ C(O)OR ａ６１ , N.R. ｃ６１ C(O)NR ｃ６１ R ｄ６１ , N.R. ｃ６１ S(O)R ｂ６１ , N.R. ｃ６１ S (O) ２ R ｂ６１ , N.R. ｃ６１ S (O) ２ NR ｃ６１ R ｄ６１ , S(O)R ｂ６１ , S(O)NR ｃ６１ R ｄ６１ , S(O) ２ R ｂ６１ , S(O) ２ NR ｃ６１ R ｄ６１ , and B.R. ｈ６１ R ｉ６１ are independently selected from Each R ７０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, halo, D, CN, NO ２ , OR ａ７０ , S.R. ａ７０ , C(O)R ｂ７０ , C(O)NR ｃ７０ R ｄ７０ , C(O)OR ａ７０ , O.C.(O.)R ｂ７０ , OC(O)NR ｃ７０ R ｄ７０ , N.R. ｃ７０ R ｄ７０ , N.R. ｃ７０ C(O)R ｂ７０ , N.R. ｃ７０ C(O)OR ａ７０ , N.R. ｃ７０ C(O)NR ｃ７０ R ｄ７０ , N.R. ｃ７０ S(O)R ｂ７０ , N.R. ｃ７０ S (O) ２ R ｂ７０ , N.R. ｃ７０ S (O) ２ NR ｃ７０ R ｄ７０ , S(O)R ｂ７０ , S(O)NR ｃ７０ R ｄ７０ , S(O) ２ R ｂ７０ , S(O) ２ NR ｃ７０ R ｄ７０ , and B.R. ｈ７０ R ｉ７０ are independently selected from R ａ１ , R ｂ１ , R ｃ１ , and R ｄ１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ｇ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ１ and R ｄ１ together with the N atom to which they are attached, form R ｇ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ１ and R ｉ１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ１ and R ｉ１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２ , R ｂ２ , R ｃ２ , and R ｄ２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２３ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２ and R ｄ２ together with the N atom to which they are attached, form R ２３ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ２ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ２ and R ｉ２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２ and R ｉ２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３ , R ｂ３ , R ｃ３ , and R ｄ３ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ３０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３ and R ｄ３ together with the N atom to which they are attached, form R ３０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ３ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ３ and R ｉ３ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３ and R ｉ３ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ５ , R ｂ５ , R ｃ５ , and R ｄ５ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ｇ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ５ and R ｄ５ together with the N atom to which they are attached, form R ｇ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R ｅ５ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ５ and R ｉ５ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ５ and R ｉ５ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ６ , R ｂ６ , R ｃ６ , and R ｄ６ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ６０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ６ and R ｄ６ together with the N atom to which they are attached, form R ６０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: Each R ｅ６ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ６ and R ｉ６ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ６ and R ｉ６ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ７ , R ｂ７ , R ｃ７ , and R ｄ７ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ７０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ７ and R ｄ７ together with the N atom to which they are attached, form R ７０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ７ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ７ and R ｉ７ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ７ and R ｉ７ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ１０ , R ｂ１０ , R ｃ１０ , and R ｄ１０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R １１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ１０ and R ｄ１０ together with the N atom to which they are attached, form R １１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ１０ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ１０ and R ｉ１０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ１０ and R ｉ１０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ１１ , R ｂ１１ , R ｃ１１ , and R ｄ１１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom ｃ１１ and R ｄ１１ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ｈ１１ and R ｉ１１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ１１ and R ｉ１１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２０ , R ｂ２０ , R ｃ２０ , and R ｄ２０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２０ and R ｄ２０ together with the N atom to which they are attached, form R ２１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: Each R ｅ２０ are H, CN, and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C １～６ Alkylthio, C １～６ Alkylsulfonyl, C １～６ Alkylcarbonyl, C １～６ Alkylaminosulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, aminosulfonyl, C １～６ Alkylaminosulfonyl, and di(C １～６ independently selected from: (alkyl)aminosulfonyl; R ｈ２０ and R ｉ２０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２０ and R ｉ２０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２１ , R ｂ２１ , R ｃ２１ , and R ｄ２１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ２２ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２１ and R ｄ２１ together with the N atom to which they are attached, form R ２２ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ２１ and R ｉ２１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２１ and R ｉ２１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２２ , R ｂ２２ , R ｃ２２ , and R ｄ２２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ independently selected from haloalkyl; R ｈ２２ and R ｉ２２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２２ and R ｉ２２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ２３ , R ｂ２３ , R ｃ２３ , and R ｄ２３ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom ｃ２３ and R ｄ２３ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ｈ２３ and R ｉ２３ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ２３ and R ｉ２３ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３０ , R ｂ３０ , R ｃ３０ , and R ｄ３０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ３１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３０ and R ｄ３０ together with the N atom to which they are attached, form R ３１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ｈ３０ and R ｉ３０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３０ and R ｉ３０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３１ , R ｂ３１ , R ｃ３１ , and R ｄ３１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl are each optionally represented by R ３２ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３１ and R ｄ３１ together with the N atom to which they are attached, form R ３２ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ｈ３１ and R ｉ３１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３１ and R ｉ３１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ３２ , R ｂ３２ , R ｃ３２ , and R ｄ３２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ independently selected from haloalkyl; Alternatively, any R bonded to the same N atom ｃ３２ and R ｄ３２ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ｈ３２ and R ｉ３２ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ３２ and R ｉ３２ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ６０ , R ｂ６０ , R ｃ６０ , and R ｄ６０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ６１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ６０ and R ｄ６０ together with the N atom to which they are attached, form R ６１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ｈ６０ and R ｉ６０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ６０ and R ｉ６０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ６１ , R ｂ６１ , R ｃ６１ , and R ｄ６１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom ｃ６１ and R ｄ６１ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ｈ６１ and R ｉ６１ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ６１ and R ｉ６１ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; R ａ７０ , R ｂ７０ , R ｃ７０ , and R ｄ７０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ independently selected from aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom ｃ７０ and R ｄ７０ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ｈ７０ and R ｉ７０ are OH and C, respectively. １～６ Alkoxy, and C １～６ haloalkoxy, or any R bonded to the same B atom ｈ７０ and R ｉ７０ together with the B atoms to which they are attached, form C １～６ Alkyl and C １～６ forming a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl; Each R ｇ D, OH, NO ２ , CN, Halo, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ Cycloalkyl, C ３～６ Cycloalkyl-C １～２ Alkylene, C １～６ Alkoxy, C １～６ Haloalkoxy, C １～３ Alkoxy-C １～３ Alkyl, C １～３ Alkoxy-C １～３ Alkoxy, HO-C １～３ Alkoxy, HO-C １～３ Alkyl, cyano-C １～３ Alkyl, H ２ N-C １～３ Alkyl, amino, C １～６ Alkylamino, di(C １～６ alkyl) amino, thio, C １～６ Alkylthio, C １～６ Alkylsulfinyl, C １～６ Alkyl sulfonyl, carbamyl, C １～６ Alkylcarbamyl, di(C １～６ alkyl) carbamyl, carboxy, C １～６ Alkylcarbonyl, C １～６ Alkoxycarbonyl, C １～６ Alkylcarbonylamino, C １～６ Alkoxycarbonylamino, C １～６ Alkylcarbonyloxy, aminocarbonyloxy, C １～６ Alkylaminocarbonyloxy, di(C １～６ alkyl)aminocarbonyloxy, C １～６ Alkyl sulfonyl amino, amino sulfonyl, C １～６ Alkylaminosulfonyl, di(C １～６ alkyl)aminosulfonyl, aminosulfonylamino, C １～６ Alkylaminosulfonylamino, di(C １～６ alkyl)aminosulfonylamino, aminocarbonylamino, C １～６ Alkylaminocarbonylamino, and di(C １～６ alkyl)aminocarbonylamino; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

3. When the compound of formula I is a compound of formula II: 【Chemistry 8】 (In the formula, -AR １ =BR ２ - is -N=CR ２ - and - CR １ =N-; X is N and CR ５ Selected from: Y is N and CR ６ Selected from: R １ H, D, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5-10 membered heteroaryl, halo, CN, OR ａ１ , S.R. ａ１ , C(O)R ｂ１ , C(O)NR ｃ１ R ｄ１ , C(O)OR ａ１ , O.C.(O.)R ｂ１ , OC(O)NR ｃ１ R ｄ１ , N.R. ｃ１ R ｄ１ , N.R. ｃ１ C(O)R ｂ１ , N.R. ｃ１ C(O)OR ａ１ , N.R. ｃ１ C(O)NR ｃ１ R ｄ１ , N.R. ｃ１ S (O) ２ R ｂ１ , N.R. ｃ１ S (O) ２ NR ｃ１ R ｄ１ , S(O) ２ R ｂ１ , and S(O) ２ NR ｃ１ R ｄ１ Selected from: R ２ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ２ , S.R. ａ２ , C(O)R ｂ２ , C(O)NR ｃ２ R ｄ２ , C(O)OR ａ２ , O.C.(O.)R ｂ２ , OC(O)NR ｃ２ R ｄ２ , N.R. ｃ２ R ｄ２ , N.R. ｃ２ C(O)R ｂ２ , N.R. ｃ２ C(O)OR ａ２ , N.R. ｃ２ C(O)NR ｃ２ R ｄ２ , N.R. ｃ２ S (O) ２ R ｂ２ , N.R. ｃ２ S (O) ２ NR ｃ２ R ｄ２ , S(O) ２ R ｂ２ , and S(O) ２ NR ｃ２ R ｄ２ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２３ substituted with 1, 2, 3, or 4 substituents independently selected from Cy １ is C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 6- to 10-membered heteroaryl, wherein said 4- to 10-membered heterocycloalkyl and 6- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; ring-forming carbon atoms of the 6- to 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 6- to 10-membered heteroaryl are each optionally represented by R １０ substituted with 1, 2, 3, or 4 substituents independently selected from R ４ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ３ , S.R. ａ３ , C(O)R ｂ３ , C(O)NR ｃ３ R ｄ３ , C(O)OR ａ３ , O.C.(O.)R ｂ３ , OC(O)NR ｃ３ R ｄ３ , N.R. ｃ３ R ｄ３ , N.R. ｃ３ C(O)R ｂ３ , N.R. ｃ３ C(O)OR ａ３ , N.R. ｃ３ C(O)NR ｃ３ R ｄ３ , N.R. ｃ３ S (O) ２ R ｂ３ , N.R. ｃ３ S (O) ２ NR ｃ３ R ｄ３ , S(O) ２ R ｂ３ , and S(O) ２ NR ｃ３ R ｄ３ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３０ substituted with 1, 2, 3, or 4 substituents independently selected from R ５ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ５ , S.R. ａ５ , C(O)R ｂ５ , C(O)NR ｃ５ R ｄ５ , C(O)OR ａ５ , O.C.(O.)R ｂ５ , OC(O)NR ｃ５ R ｄ５ , N.R. ｃ５ R ｄ５ , N.R. ｃ５ C(O)R ｂ５ , N.R. ｃ５ C(O)OR ａ５ , N.R. ｃ５ C(O)NR ｃ５ R ｄ５ , N.R. ｃ５ S (O) ２ R ｂ５ , N.R. ｃ５ S (O) ２ NR ｃ５ R ｄ５ , S(O) ２ R ｂ５ , and S(O) ２ NR ｃ５ R ｄ５ Selected from: R ６ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ６ , S.R. ａ６ , C(O)R ｂ６ , C(O)NR ｃ６ R ｄ６ , C(O)OR ａ６ , O.C.(O.)R ｂ６ , OC(O)NR ｃ６ R ｄ６ , N.R. ｃ６ R ｄ６ , N.R. ｃ６ C(O)R ｂ６ , N.R. ｃ６ C(O)OR ａ６ , N.R. ｃ６ C(O)NR ｃ６ R ｄ６ , N.R. ｃ６ S (O) ２ R ｂ６ , N.R. ｃ６ S (O) ２ NR ｃ６ R ｄ６ , S(O) ２ R ｂ６ , and S(O) ２ NR ｃ６ R ｄ６ and C is selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ６０ substituted with 1, 2, 3, or 4 substituents independently selected from R ７ is H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ７ , S.R. ａ７ , C(O)R ｂ７ , C(O)NR ｃ７ R ｄ７ , C(O)OR ａ７ , O.C.(O.)R ｂ７ , OC(O)NR ｃ７ R ｄ７ , N.R. ｃ７ R ｄ７ , N.R. ｃ７ C(O)R ｂ７ , N.R. ｃ７ C(O)OR ａ７ , N.R. ｃ７ C(O)NR ｃ７ R ｄ７ , N.R. ｃ７ S (O) ２ R ｂ７ , N.R. ｃ７ S (O) ２ NR ｃ７ R ｄ７ , S(O) ２ R ｂ７ , and S(O) ２ NR ｃ７ R ｄ７ Selected from: Cy ２ is C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said 4- to 10-membered heterocycloalkyl and 5- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; ring-forming carbon atoms of the 5- to 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２０ substituted with 1, 2, 3, or 4 substituents independently selected from Each R １０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ１０ , S.R. ａ１０ , C(O)R ｂ１０ , C(O)NR ｃ１０ R ｄ１０ , C(O)OR ａ１０ , O.C.(O.)R ｂ１０ , OC(O)NR ｃ１０ R ｄ１０ , N.R. ｃ１０ R ｄ１０ , N.R. ｃ１０ C(O)R ｂ１０ , N.R. ｃ１０ C(O)OR ａ１０ , N.R. ｃ１０ C(O)NR ｃ１０ R ｄ１０ , N.R. ｃ１０ S (O) ２ R ｂ１０ , N.R. ｃ１０ S (O) ２ NR ｃ１０ R ｄ１０ , S(O) ２ R ｂ１０ , and S(O) ２ NR ｃ１０ R ｄ１０ are independently selected from Each R ２０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ２０ , S.R. ａ２０ , C(O)R ｂ２０ , C(O)NR ｃ２０ R ｄ２０ , C(O)OR ａ２０ , O.C.(O.)R ｂ２０ , OC(O)NR ｃ２０ R ｄ２０ , N.R. ｃ２０ R ｄ２０ , N.R. ｃ２０ C(O)R ｂ２０ , N.R. ｃ２０ C(O)OR ａ２０ , N.R. ｃ２０ C(O)NR ｃ２０ R ｄ２０ , N.R. ｃ２０ S (O) ２ R ｂ２０ , N.R. ｃ２０ S (O) ２ NR ｃ２０ R ｄ２０ , S(O) ２ R ｂ２０ , S(O) ２ NR ｃ２０ R ｄ２０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ２１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ２１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ２１ , S.R. ａ２１ , C(O)R ｂ２１ , C(O)NR ｃ２１ R ｄ２１ , C(O)OR ａ２１ , O.C.(O.)R ｂ２１ , OC(O)NR ｃ２１ R ｄ２１ , N.R. ｃ２１ R ｄ２１ , N.R. ｃ２１ C(O)R ｂ２１ , N.R. ｃ２１ C(O)OR ａ２１ , N.R. ｃ２１ C(O)NR ｃ２１ R ｄ２１ , N.R. ｃ２１ S (O) ２ R ｂ２１ , N.R. ｃ２１ S (O) ２ NR ｃ２１ R ｄ２１ , S(O) ２ R ｂ２１ , and S(O) ２ NR ｃ２１ R ｄ２１ are independently selected from Each R ２３ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ２３ , S.R. ａ２３ , C(O)R ｂ２３ , C(O)NR ｃ２３ R ｄ２３ , C(O)OR ａ２３ , O.C.(O.)R ｂ２３ , OC(O)NR ｃ２３ R ｄ２３ , N.R. ｃ２３ R ｄ２３ , N.R. ｃ２３ C(O)R ｂ２３ , N.R. ｃ２３ C(O)OR ａ２３ , N.R. ｃ２３ C(O)NR ｃ２３ R ｄ２３ , N.R. ｃ２３ S (O) ２ R ｂ２３ , N.R. ｃ２３ S (O) ２ NR ｃ２３ R ｄ２３ , S(O) ２ R ｂ２３ , and S(O) ２ NR ｃ２３ R ｄ２３ are independently selected from Each R ３０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ３０ , S.R. ａ３０ , C(O)R ｂ３０ , C(O)NR ｃ３０ R ｄ３０ , C(O)OR ａ３０ , O.C.(O.)R ｂ３０ , OC(O)NR ｃ３０ R ｄ３０ , N.R. ｃ３０ R ｄ３０ , N.R. ｃ３０ C(O)R ｂ３０ , N.R. ｃ３０ C(O)OR ａ３０ , N.R. ｃ３０ C(O)NR ｃ３０ R ｄ３０ , N.R. ｃ３０ S (O) ２ R ｂ３０ , N.R. ｃ３０ S (O) ２ NR ｃ３０ R ｄ３０ , S(O) ２ R ｂ３０ , and S(O) ２ NR ｃ３０ R ｄ３０ and wherein C is independently selected from １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, and 5- to 10-membered heteroaryl-C １～３ Each alkylene is optionally selected from R ３１ substituted with 1, 2, 3, or 4 substituents independently selected from Each R ３１ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ３１ , S.R. ａ３１ , C(O)R ｂ３１ , C(O)NR ｃ３１ R ｄ３１ , C(O)OR ａ３１ , O.C.(O.)R ｂ３１ , OC(O)NR ｃ３１ R ｄ３１ , N.R. ｃ３１ R ｄ３１ , N.R. ｃ３１ C(O)R ｂ３１ , N.R. ｃ３１ C(O)OR ａ３１ , N.R. ｃ３１ C(O)NR ｃ３１ R ｄ３１ , N.R. ｃ３１ S (O) ２ R ｂ３１ , N.R. ｃ３１ S (O) ２ NR ｃ３１ R ｄ３１ , S(O) ２ R ｂ３１ , and S(O) ２ NR ｃ３１ R ｄ３１ are independently selected from Each R ６０ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, C ３～１０ Cycloalkyl-C １～３ alkylene, 4- to 10-membered heterocycloalkyl-C １～３ Alkylene, C ６～１０ Aryl-C １～３ alkylene, 5- to 10-membered heteroaryl-C １～３ Alkylene, Halo, D, CN, OR ａ６０ , S.R. ａ６０ , C(O)R ｂ６０ , C(O)NR ｃ６０ R ｄ６０ , C(O)OR ａ６０ , O.C.(O.)R ｂ６０ , OC(O)NR ｃ６０ R ｄ６０ , N.R. ｃ６０ R ｄ６０ , N.R. ｃ６０ C(O)R ｂ６０ , N.R. ｃ６０ C(O)OR ａ６０ , N.R. ｃ６０ C(O)NR ｃ６０ R ｄ６０ , N.R. ｃ６０ S (O) ２ R ｂ６０ , N.R. ｃ６０ S (O) ２ NR ｃ６０ R ｄ６０ , S(O) ２ R ｂ６０ , and S(O) ２ NR ｃ６０ R ｄ６０ are independently selected from R ａ１ , R ｂ１ , R ｃ１ , and R ｄ１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ independently selected from aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom ｃ１ and R ｄ１ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ａ２ , R ｂ２ , R ｃ２ , and R ｄ２ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２３ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２ and R ｄ２ together with the N atom to which they are attached, form R ２３ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ａ３ , R ｂ３ , R ｃ３ , and R ｄ３ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ３０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３ and R ｄ３ together with the N atom to which they are attached, form R ３０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ａ５ , R ｂ５ , R ｃ５ , and R ｄ５ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ independently selected from aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom ｃ５ and R ｄ５ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ａ６ , R ｂ６ , R ｃ６ , and R ｄ６ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ６０ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ６ and R ｄ６ together with the N atom to which they are attached, form R ６０ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from: R ａ７ , R ｂ７ , R ｃ７ , and R ｄ７ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ independently selected from aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom ｃ７ and R ｄ７ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ａ１０ , R ｂ１０ , R ｃ１０ , and R ｄ１０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ independently selected from aryl, and 5-10 membered heteroaryl; Alternatively, any R bonded to the same N atom ｃ１０ and R ｄ１０ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ａ２０ , R ｂ２０ , R ｃ２０ , and R ｄ２０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ２１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ２０ and R ｄ２０ together with the N atom to which they are attached, form R ２１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ａ２１ , R ｂ２１ , R ｃ２１ , and R ｄ２１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom ｃ２１ and R ｄ２１ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ａ２３ , R ｂ２３ , R ｃ２３ , and R ｄ２３ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom ｃ２３ and R ｄ２３ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ａ３０ , R ｂ３０ , R ｃ３０ , and R ｄ３０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 5- to 10-membered heteroaryl are each optionally represented by R ３１ or substituted with 1, 2, 3, or 4 substituents independently selected from Alternatively, any R bonded to the same N atom ｃ３０ and R ｄ３０ together with the N atom to which they are attached, form R ３１ forming a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from: R ａ３１ , R ｂ３１ , R ｃ３１ , and R ｄ３１ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～６ independently selected from cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 4- to 7-membered heterocycloalkyl; Alternatively, any R bonded to the same N atom ｃ３１ and R ｄ３１ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group; R ａ６０ , R ｂ６０ , R ｃ６０ , and R ｄ６０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; and Alternatively, any R bonded to the same N atom ｃ６０ and R ｄ６０ together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group.

2. The compound of claim 1, wherein:

4. -AR １ =BR ２ - is -N=CR ２ - and - CR １ =N-; X is N and CR ５ Selected from: Y is N and CR ６ Selected from: R １ H, D, C １～６ Alkyl, and C １～６ haloalkyl; R ２ is H, C １～６ Alkyl, C １～６ Haloalkyl, Halo, D, CN, OR ａ２ , and N.R. ｃ２ R ｄ２ and C is selected from １～６ The alkyl is optionally R ２３ substituted with 1 or 2 substituents independently selected from Cy １ is C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 6- to 10-membered heteroaryl, wherein said 4- to 10-membered heterocycloalkyl and 6- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and the ring-forming carbon atoms of the 6- to 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 6- to 10-membered heteroaryl are each optionally represented by R １０ substituted with 1, 2, or 3 substituents independently selected from R ４ is H, C １～６ Alkyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, D, CN, OR ａ３ , C(O)NR ｃ３ R ｄ３ , and N.R. ｃ３ R ｄ３ and C is selected from １～６ Alkyl, C ３～１０ Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally selected from R ３０ substituted with 1 or 2 substituents independently selected from R ５ is H, C １～６ Alkyl, C １～６ Haloalkyl, Halo, D, CN, OR ａ５ , and N.R. ｃ５ R ｄ５ Selected from: R ６ is H, C １～６ Alkyl, C １～６ Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR ａ６ , and N.R. ｃ６ R ｄ６ and C is selected from １～６ The alkyl and 4- to 10-membered heterocycloalkyl are each optionally represented by R ６０ substituted with 1 or 2 substituents independently selected from R ７ is H, C １～６ Alkyl, and C １～６ Haloalkyl, Halo, D, CN, OR ａ７ , and N.R. ｃ７ R ｄ７ Selected from: Cy ２ is selected from 4- to 7-membered heterocycloalkyl having at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, a ring-forming carbon atom of said 4- to 7-membered heterocycloalkyl optionally substituted by oxo to form a carbonyl group, and said 4- to 7-membered heterocycloalkyl optionally selected from R ２０ substituted with 1 or 2 substituents independently selected from Each R １０ is C １～６ Alkyl, C １～６ Haloalkyl, Halo, D, CN, OR ａ１０ , C(O)NR ｃ１０ R ｄ１０ , and N.R. ｃ１０ R ｄ１０ are independently selected from Each R ２０ is C １～６ Alkyl, C １～６ Haloalkyl, Halo, D, CN, OR ａ２０ , C(O)R ｂ２０ , C(O)NR ｃ２０ R ｄ２０ , and N.R. ｃ２０ R ｄ２０ and wherein C is independently selected from １～６ The alkyl is optionally R ２１ substituted with 1 or 2 substituents independently selected from Each R ２１ is C １～６ Alkyl, C １～６ Haloalkyl, Halo, D, CN, OR ａ２１ , and N.R. ｃ２１ R ｄ２１ are independently selected from Each R ２３ is C １～６ Alkyl, C １～６ Haloalkyl, Halo, D, CN, OR ａ２３ , and N.R. ｃ２３ R ｄ２３ are independently selected from Each R ３０ is C １～６ Alkyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR ａ３０ , C(O)NR ｃ３０ R ｄ３０ , and N.R. ｃ３０ R ｄ３０ and wherein C is independently selected from １～６ Alkyl, C ３～１０ The cycloalkyl and 4- to 10-membered heterocycloalkyl are each optionally selected from R ３１ substituted with 1 or 2 substituents independently selected from Each R ３１ is C １～６ Alkyl, C １～６ Haloalkyl, Halo, D, CN, OR ａ３１ , and N.R. ｃ３１ R ｄ３１ are independently selected from Each R ６０ is C １～６ Alkyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR ａ６０ , C(O)R ｂ６０ , C(O)NR ｃ６０ R ｄ６０ , C(O)OR ａ６０ , and N.R. ｃ６０ R ｄ６０ are independently selected from R ａ２ , R ｃ２ , and R ｄ２ are H and C, respectively. １～６ Alkyl, and C １～６ haloalkyl; １～６ The alkyl is optionally R ２３ substituted with 1 or 2 substituents independently selected from R ａ３ , R ｂ３ , R ｃ３ , and R ｄ３ are H and C, respectively. １～６ Alkyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl; １～６ Alkyl, C ３～１０ Cycloalkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally selected from R ３０ or substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom ｃ３ and R ｄ３ together with the N atom to which they are attached, form R ３０ forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R ａ５ , R ｃ５ , and R ｄ５ are H and C, respectively. １～６ Alkyl, and C １～６ independently selected from haloalkyl; R ａ６ , R ｃ６ , and R ｄ６ are H and C, respectively. １～６ Alkyl, and C １～６ haloalkyl; １～６ The alkyl is optionally R ６０ substituted with 1 or 2 substituents independently selected from R ａ７ , R ｃ７ , and R ｄ７ are H and C, respectively. １～６ Alkyl, and C １～６ independently selected from haloalkyl; R ａ１０ , R ｂ１０ , R ｃ１０ , and R ｄ１０ are H and C, respectively. １～６ Alkyl, and C １～６ independently selected from haloalkyl; R ａ２０ , R ｂ２０ , R ｃ２０ , and R ｄ２０ are H and C, respectively. １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C １～６ haloalkyl; １～６ Alkyl, C ２～６ Alkenyl, and C ２～６ Each alkynyl is optionally selected from R ２１ substituted with 1, 2, or 3 substituents independently selected from R ａ２１ , R ｃ２１ , and R ｄ２１ are H and C, respectively. １～６ Alkyl, and C １～６ independently selected from haloalkyl; R ａ２３ , R ｃ２３ , and R ｄ２３ are H and C, respectively. １～６ Alkyl, and C １～６ independently selected from haloalkyl; R ａ３０ , R ｃ３０ , and R ｄ３０ are H and C, respectively. １～６ Alkyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, and 4- to 10-membered heterocycloalkyl; １～６ Alkyl, C ３～１０ The cycloalkyl and 4- to 10-membered heterocycloalkyl are each optionally selected from R ３１ or substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom ｃ３０ and R ｄ３０ together with the N atom to which they are attached, form R ３１ forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R ａ３１ , R ｃ３１ , and R ｄ３１ are H and C, respectively. １～６ Alkyl, C １～６ independently selected from haloalkyl; R ａ６０ , R ｂ６０ , R ｃ６０ , and R ｄ６０ are H and C, respectively. １～６ Alkyl, C １～６ Haloalkyl, C ３～１０ cycloalkyl, and 4- to 10-membered heterocycloalkyl; and Alternatively, any R bonded to the same N atom ｃ６０ and R ｄ６０ together with the N atom to which they are attached form a 4-, 5-, or 6-membered heterocycloalkyl group; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

5. -AR １ =BR ２ - is -N=CR ２ - and - CR １ =N-; X is N and CR ５ Selected from: Y is N and CR ６ Selected from: R １ is H; R ２ is H, C １～６ Alkyl, and C １～６ haloalkyl, wherein C １～６ The alkyl is optionally R ２３ substituted with 1 or 2 substituents independently selected from Cy １ is C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 6- to 10-membered heteroaryl, wherein the 4- to 10-membered heterocycloalkyl and the 6- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 6- to 10-membered heteroaryl are each optionally represented by R １０ substituted with 1 or 2 substituents independently selected from R ４ is H, C １～６ Alkyl, C １～６ haloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, CN, OR ａ３ , and N.R. ｃ３ R ｄ３ and C is selected from １～６ The alkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally selected from R ３０ substituted with 1 or 2 substituents independently selected from R ５ is H, C １～６ Alkyl, and C １～６ haloalkyl; R ６ is H, C １～６ Alkyl, C １～６ haloalkyl, and 4- to 10-membered heterocycloalkyl; １～６ Alkyl and 4- to 10-membered heterocycloalkyl are optionally R ６０ substituted with 1 or 2 substituents independently selected from R ７ is H, C １～６ Alkyl, and C １～６ selected from haloalkyl, halo, D, and CN; Cy ２ is selected from 4- to 6-membered heterocycloalkyl having at least one ring-forming carbon atom and 1 or 2 ring-forming heteroatoms independently selected from N and O, and the 4- to 6-membered heterocycloalkyl optionally has R ２０ substituted with 1 or 2 substituents independently selected from Each R １０ is C １～６ Alkyl, C １～６ Haloalkyl, halo, D, CN, and OR ａ１０ are independently selected from Each R ２０ is C １～６ Alkyl, C １～６ Haloalkyl, halo, D, CN, and C(O)R ｂ２０ and wherein C is independently selected from １～６ The alkyl is optionally R ２１ substituted with 1 or 2 substituents independently selected from Each R ２１ is C １～６ Alkyl, C １～６ independently selected from haloalkyl, halo, D, and CN; Each R ２３ is C １～６ Alkyl, C １～６ independently selected from haloalkyl, halo, D, and CN; Each R ３０ is C １～６ Alkyl, C １～６ Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR ａ３０ , C(O)NR ｃ３０ R ｄ３０ , and N.R. ｃ３０ R ｄ３０ and wherein C is independently selected from １～６ The alkyl and 4- to 10-membered heterocycloalkyl are each optionally represented by R ３１ substituted with 1 or 2 substituents independently selected from Each R ３１ is C １～６ Alkyl, C １～６ independently selected from haloalkyl, halo, D, and CN; Each R ６０ is C １～６ Alkyl, C １～６ Haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR ａ６０ , C(O)R ｂ６０ , C(O)NR ｃ６０ R ｄ６０ , C(O)OR ａ６０ , and N.R. ｃ６０ R ｄ６０ are independently selected from R ａ３ , R ｃ３ , and R ｄ３ are H and C, respectively. １～６ Alkyl, C １～６ haloalkyl, and 4- to 10-membered heterocycloalkyl; １～６ The alkyl and 4- to 10-membered heterocycloalkyl are each optionally represented by R ３０ or substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom ｃ３ and R ｄ３ together with the N atom to which they are attached, form R ３０ forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: Each R ａ１０ is H, C １～６ Alkyl, and C １～６ independently selected from haloalkyl; Each R ｂ２０ is C ２～６ Alkenyl, and C ２～６ alkynyl, wherein C ２～６ Alkenyl, and C ２～６ Each alkynyl is optionally selected from R ２１ substituted with 1, 2, or 3 substituents independently selected from R ａ３０ , R ｃ３０ , and R ｄ３０ are H and C, respectively. １～６ Alkyl, C １～６ haloalkyl, and 4- to 10-membered heterocycloalkyl; １～６ The alkyl and 4- to 10-membered heterocycloalkyl are each optionally represented by R ３１ or substituted with 1 or 2 substituents independently selected from: Alternatively, any R bonded to the same N atom ｃ３０ and R ｄ３０ together with the N atom to which they are attached, form R ３１ forming a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from: R ａ６０ , R ｂ６０ , R ｃ６０ , and R ｄ６０ are H and C, respectively. １～６ Alkyl, C １～６ independently selected from haloalkyl, and 4- to 10-membered heterocycloalkyl; and Alternatively, any R bonded to the same N atom ｃ６０ and R ｄ６０ together with the N atom to which they are attached form a 4-, 5-, or 6-membered heterocycloalkyl group; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

6. -AR １ =BR ２ - is -N=CR ２ - and - CR １ =N-; X is N or CR ５ and Y is N or CR ６ and R １ is H; R ２ is R ２３ C optionally substituted with 1, 2, or 3 substituents independently selected from １～６ is alkyl; Cy １ is selected from naphthyl, benzothiazolyl, chromyl, phenyl, indolyl, indolinyl, tetrahydroquinolinyl, dihydroindenyl, quinolinyl, and indazolyl, all of which are optionally coupled with R １０ substituted with 1, 2, or 3 substituents independently selected from R ４ is C １～６ alkyl, 4- to 10-membered heterocycloalkyl, 6- to 10-membered heteroaryl, and OR ａ３ and C is selected from １～６ The alkyl, 4- to 10-membered heterocycloalkyl, and 6- to 10-membered heteroaryl are each optionally selected from R ３０ substituted with 1, 2, or 3 substituents independently selected from R ５ is H; R ６ is C １～６ alkyl, 4- to 10-membered heterocycloalkyl, dihydroindolizinonyl; １～６ Alkyl and 4- to 10-membered heterocycloalkyl are optionally R ６０ substituted with 1, 2, or 3 substituents independently selected from R ７ is C １～３ alkyl or halo; Cy ２ is R ２０ is a 4- to 14-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from Each R １０ is C １～６ independently selected from alkyl, halo, CN, and OH; Each R ２０ is C １～６ Alkyl, and C(O)R ｂ２０ and wherein C is independently selected from １～６ The alkyl is optionally R ２１ substituted with 1, 2, or 3 substituents independently selected from Each R ２１ is independently selected from halo and CN; Each R ２３ is CN; Each R ３０ is C １～６ Alkyl, 4-10 membered heterocycloalkyl, C(O)NR ｃ３０ R ｄ３０ , and N.R. ｃ３０ R ｄ３０ wherein said 4 to 10 membered heterocycloalkyl is optionally selected from R ３１ substituted with 1, 2, or 3 substituents independently selected from Each R ３１ is C １～６ independently selected from alkyl, and halo; Each R ６０ represents 4-10 membered heterocycloalkyl, pyridinonyl, C(O)NR ｃ６０ R ｄ６０ , C(O)R ａ６０ , and C(O)OR ａ６０ are independently selected from Each R ａ３ is R ３０ C optionally substituted with 1, 2, or 3 substituents independently selected from １～６ is alkyl; Each R ｂ２０ is R ２１ C optionally substituted with 1, 2, or 3 substituents independently selected from ２～６ alkenyl; R ｃ３０ and R ｄ３０ are each independently H or C １～６ is alkyl; R ａ６０ , R ｃ６０ , and R ｄ６０ are each independently H or C １～６ is alkyl, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof. 【Request 7】 【Chemical 9】 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein represents a double bond.

8. -AR １ =BR ２ - is -N=CR ２ 2. The compound of claim 1, wherein: -, or a pharmaceutically acceptable salt thereof.

9. -AR １ =BR ２ - but -CR １ 2. The compound of claim 1, wherein =N-, or a pharmaceutically acceptable salt thereof.

10. X is CR ５ and Y is CR ６ That is, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

11. X is N; Y is CR ６ That is, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

12. X is N; Y is N; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

13. R １ is H, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

14. R ２ But H, C １～６ Alkyl, and C １～６ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from haloalkyl.

15. R ２ is optionally substituted with CN １～６ is alkyl, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

16. Cy １ is C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 6- to 10-membered heteroaryl, wherein said 4- to 10-membered heterocycloalkyl and 6- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; ring-forming carbon atoms of the 6- to 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said C ３～１０ cycloalkyl, 4- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 6- to 10-membered heteroaryl are each optionally represented by R １０ substituted with 1 or 2 substituents independently selected from 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

17. Cy １ is a 5- to 10-membered heterocycloalkyl, C ６～１０ aryl, and 6- to 10-membered heteroaryl, wherein said 5- to 10-membered heterocycloalkyl and 6- to 10-membered heteroaryl each have at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, and said N and S are optionally oxidized; ring-forming carbon atoms of the 6- to 10-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally substituted by oxo to form a carbonyl group; and said 5- to 10-membered heterocycloalkyl, C ６～１０ The aryl and 6- to 10-membered heteroaryl are each optionally represented by R １０ substituted with 1 or 2 substituents independently selected from 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

18. [Catalog 10] is a double bond, and R ３ does not exist, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

19. R ４ is C １～６ alkyl, 4- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, and OR ａ３ and C is selected from １～６ The alkyl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each optionally selected from R ３０ substituted with 1 or 2 substituents independently selected from 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

20. R ５ is H, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

21. R ６ is C １～６ alkyl, and 4- to 10-membered heterocycloalkyl; １～６ The alkyl and 4- to 10-membered heterocycloalkyl are each optionally represented by R ６０ substituted with 1 or 2 substituents independently selected from 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

22. R ７ But H, C １～３ selected from alkyl, and halo; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

23. Cy ２ is R ２０ is a 5- to 10-membered heterocycloalkyl optionally substituted with 1 or 2 substituents independently selected from 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

24. Cy ２ is R ２０ is a 4- to 6-membered heterocycloalkyl optionally substituted with 1 or 2 substituents independently selected from 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

25. Each R １０ But C １～６ independently selected from alkyl, halo, CN, and OH; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

26. Each R ２０ is C １～６ Alkyl, and C(O)C ２～６ alkenyl, wherein C １～６ Alkyl, and C ２～６ each alkenyl is optionally substituted with 1 or 2 substituents independently selected from CN and halo; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

27. Each R ３０ is C １～６ Alkyl, 4-10 membered heterocycloalkyl, C(O)NR ｃ３０ R ｄ３０ , and N.R. ｃ３０ R ｄ３０ and wherein C is independently selected from １～６ The alkyl and 4- to 10-membered heterocycloalkyl are each optionally represented by R ３１ substituted with 1 or 2 substituents independently selected from 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

28. Each R ６０ is a 4- to 10-membered heterocycloalkyl, C(O)R ｂ６０ , C(O)NR ｃ６０ R ｄ６０ , and C(O)OR ａ６０ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, independently selected from:

29. Each R ａ３ is R ３０ C optionally substituted with 1 or 2 substituents independently selected from １～６ is alkyl, Each R ３０ is C １～６ is a 4- to 10-membered heterocycloalkyl optionally substituted with 1 or 2 substituents independently selected from alkyl; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

30. R ｃ３０ and R ｄ３０ are H and C, respectively. １～６ alkyl, wherein C １～６ The alkyl is optionally R ３１ 10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, substituted with one or two substituents independently selected from:

31. R ａ６０ , R ｃ６０ , and R ｄ６０ is C １～６ 10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R is alkyl.

32. The compound of formula I is Methyl 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)propanoate; methyl 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-4-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methoxy)-7-(3-hydroxynaphthalen-1-yl)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)propanoate; 4-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-2-methyl-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-7-yl)naphthalen-2-ol; 4-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-2-methyl-4-((tetrahydro-1H-pyrrolidin-7a(5H)-yl)methoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-7-yl)naphthalen-2-ol; 3-((1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-methyl-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)methyl)oxazolidin-2-one; 3-((1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(5-fluoro-1H-indol-3-yl)-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)methyl)oxazolidin-2-one; 3-((1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(3,4-dihydroquinolin-1(2H)-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)methyl)oxazolidin-2-one; 1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(indolin-1-yl)-2-methyl-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridine; 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-imidazo[4,5-c][1,6]naphthyridin-2-yl)-N,N-dimethylpropanamide; 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(3-cyano-2,3-dihydro-1H-inden-4-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-1H-imidazo[4,5-c][1,6]naphthyridin-2-yl)-N,N-dimethylpropanamide; Methyl 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c][1,6]naphthyridin-2-yl)propanoate; 2-((2S,4S)-4-(4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-7-(5-fluoroquinolin-8-yl)-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-1-yl)-1-((E)-4-fluorobut-2-enoyl)piperidin-2-yl)acetonitrile; 2-((2S,4S)-4-(7-(5,6-dimethyl-1H-indazol-3-yl)-4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-1-yl)-1-(2-fluoroacryloyl)piperidin-2-yl)acetonitrile; 8-(1-((2S,4S)-2-(cyanomethyl)-1-(2-fluoroacryloyl)piperidin-4-yl)-4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-7-yl)-1-naphthonitrile; 8-(1-((2S,4S)-2-(cyanomethyl)-1-((E)-4-fluorobut-2-enoyl)piperidin-4-yl)-4-(3-(ethyl(methyl)amino)azetidin-1-yl)-6-fluoro-1H-[1,2,3]triazolo[4,5-c][1,6]naphthyridin-7-yl)-1-naphthonitrile; 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-7-(3-hydroxynaphthalen-1-yl)-6,8-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl)-N,N-dimethylpropanamide; and 3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-yl)-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl)-N,N-dimethylpropanamide 2. The compound of claim 1, selected from:

33. The compound of formula I is 4-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-2-methyl-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-7-yl)-6-fluoronaphthalen-2-ol; 1-((R)-2-(7-(benzo[d]thiazol-4-yl)-1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidin-1-yl)ethan-1-one; 3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)-2,3-dihydroindolizin-5(1H)-one; 1-((R)-1-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)ethyl)pyridin-2(1H)-one; (R)-2-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2,3-dichlorophenyl)-4-(3-(dimethylamino)-3-methylazetidin-1-yl)-6-fluoro-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate methyl; (R)-2-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2,3-dichlorophenyl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate; and (R)-2-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2-chloro-3-methylphenyl)-6-fluoro-4-(6-(methylcarbamoyl)pyridin-2-yl)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate 2. The compound of claim 1, selected from:

34. The compound of formula I is (R)-2-(7-(benzo[d]thiazol-4-yl)-1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-6-fluoro-4-(((S)-1-(pyrrolidin-1-yl)propan-2-yl)oxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)pyrrolidine-1-carboxylate methyl; (7aS)-5-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)tetrahydro-1H,3H-pyrrolo[1,2-c]oxazol-3-one; and 4-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(chroman-8-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-pyrrolo[3,2-c][1,6]naphthyridin-2-yl)-N,N,1-trimethyl-1H-pyrazole-3-carboxamide 2. The compound of claim 1, selected from:

35. A compound according to any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable carrier or excipient A pharmaceutical composition comprising:

36. A pharmaceutical for use in a method for inhibiting KRAS activity, comprising a compound according to any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof, the method comprising contacting a compound according to any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof, with KRAS.

37. 37. The method of claim 36, wherein said contacting comprises administering said compound to a patient.

38. A medicament comprising a compound according to any one of claims 1 to 34 or a pharmaceutically acceptable salt thereof for the treatment of a disease or disorder associated with the inhibition of KRAS interaction.

39. The pharmaceutical of claim 38, wherein the disease or disorder is an immune disorder or an inflammatory disorder.

40. The pharmaceutical composition of claim 39, wherein the immune disorder or the inflammatory disorder is a Ras-associated lymphoproliferative disorder caused by a somatic mutation of KRAS and juvenile myelomonocytic leukemia.

41. A pharmaceutical composition for the treatment of cancer, comprising a compound according to any one of claims 1 to 34 or a pharmaceutically acceptable salt thereof.

42. 42. The method of claim 41, wherein the cancer is selected from carcinoma, blood cancer, sarcoma, and glioblastoma.

43. 43. The medicament of claim 42, wherein the hematological cancer is selected from myeloproliferative neoplasms, myelodysplastic syndromes, chronic and juvenile myelomonocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, and multiple myeloma.

44. 43. The method of claim 42, wherein the carcinoma is selected from pancreatic cancer, colorectal cancer, lung cancer, bladder cancer, gastric cancer, esophageal cancer, breast cancer, head and neck cancer, cervical cancer, skin cancer, and thyroid cancer.

45. A medicament comprising the compound according to any one of claims 1 to 34 or a pharmaceutically acceptable salt thereof for the treatment of a disease or disorder associated with the inhibition of KRAS protein having the G12V mutation.

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