Lactam-substituted imidazopyridazine IL-17A modulators and uses thereof

Abstract

The present disclosure provides lactam-substituted imidazopyridazine compounds of formula (I), (II), (II-a), (II-a), (III), (IV), (IV-a), and (IV-b) or pharmaceutical compositions thereof for the modulation of IL-17A. These compounds are useful for the treatment of inflammatory conditions, such as psoriasis. TIFF2025517404000843.tif6897

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 343,756, filed May 19, 2022, and U.S. Provisional Patent Application No. 63 / 343,769, filed May 19, 2022, each of which is incorporated by reference in its entirety herein. [Background technology]

[0002] The IL-17 family consists of six cytokines (IL-17A-IL-17F). Interleukin-17A (IL-17A) is a well-established pro-inflammatory cytokine and is involved in the induction of IL-6, IL-8, G-CSF, TNF-α, IL-1β, PGE2, and IFN-γ, as well as numerous chemokines and other effectors. IL-17A can form homodimers or heterodimers with its family member IL-17F and can bind to both IL-17 receptors, IL-17RA and IL-17RC, to mediate signal transduction. IL-17A is a major pathological cytokine expressed by Th17 cells involved in inflammatory and autoimmune pathology, as well as CD8+T cells, γδ cells, NK cells, NKT cells, macrophages, and dendritic cells. In addition, IL-17A and Th17 are required for defense against various microorganisms, despite their involvement in inflammatory and autoimmune disorders. Furthermore, IL-17A can act in concert with other inflammatory cytokines, such as TNF-α, IFN-γ, and IL-1β, to mediate pro-inflammatory effects.

[0003] To date, there are several biologics (secukinumab and ixekizumab) approved to modulate IL-17A for the treatment of inflammatory diseases such as psoriasis, ankylosing spondylitis, and psoriatic arthritis. These treatments require injections into patients because they are not readily absorbed by the intestine when taken orally. Furthermore, these approved biologic treatments have high input costs for patients, limiting their availability to the patient population in need.

[0004] There are some small molecule modulators of IL-17A that are approved for oral administration. However, although they have the convenience of oral administration and lower input cost to patients, they lack the efficacy of approved biologics. Therefore, there is a need to develop potent small molecule IL-17A modulators for the treatment of inflammatory diseases and other related disorders. Summary of the Invention

[0005] In certain aspects, the present disclosure provides a compound represented by the structure of formula (I):

[0006] [ka] or a pharma- ceutically acceptable salt thereof, wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, each of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocyclic ring is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -N(R 12 )S(O) 2 R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN; C 1~10 Alkyl and C 3~10 Carbocyclic rings, each of which is halogen, -OR 12 , -SR 12 , -N(R 12 )2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, C 3~10 is optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle; 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -NO 2 , =O, =N(R 12 ), and -CN, 1~10 Alkyl and C 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from Each R 5 shall, for each occurrence, consist of (i), (ii), and (iii) of the following: (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13, -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; and (iii) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN; and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 )2 , -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; are independently selected from Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2, =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), -CN; and halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; or The Two R's 1 The substituents, taken together, are C 3~6 can form a carbocyclic ring, C 3~6 The carbocyclic ring is Halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A, -C(O)N(R 18A ) 2 , -NO 2 , =O, =S, =N(R 18A ), -CN; and Halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , =O, =S, =N(R 18A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and optionally substituted with one or more substituents independently selected from R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN; and Halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; is selected from Each R 3 For each occurrence, Hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN; and Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; or Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2, -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17A )C(O)R 17A , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN; and Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; are independently selected from R 11 , R 11A , R 12 , R 13 , R 14 , R 14A , R 15 , R 16 , R 17 , R 17A , and R 18A For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、-NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 Carbocyclic and 3- to 10-membered heterocyclic rings; are independently selected from n is selected from 1 and 2; m is selected from 0, 1, and 2; p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0007] In certain aspects, the present disclosure provides a compound represented by the structure of formula (III):

[0008] [ka] or a pharma- ceutically acceptable salt thereof, wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, each of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A )2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -N(R 12 )S(O) 2 R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R12 ), -CN; C 1~10 Alkyl and C 3~10 Carbocyclic rings, each of which is halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, C 3~10 is optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle; 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -NO 2 , =O, =N(R 12 ), and -CN, 1~10 Alkyl and C 3~10 and optionally substituted with one or more substituents independently selected from carbocycles; Each R 5 shall, for each occurrence, consist of (i), (ii), and (iii) of the following: (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , -CN; (ii) C 1~10 is an alkyl group, Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; and (iii) C 3~10 A carbocyclic ring, Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O)2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN; and Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl, C optionally substituted with one or more substituents independently selected from 3~10 Carbocyclic; are independently selected from Each R 1 For each occurrence, halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 independently selected from alkyl, R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6alkyl, Each R 3 is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 independently selected from alkyl, Each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17, -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN, optionally substituted with one or more substituents independently selected from 1~10 independently selected from alkyl, R 11 , R 11A , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2, ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 Carbocyclic and 3- to 10-membered heterocyclic rings; are independently selected from n is selected from 1 and 2; m is selected from 0, 1, and 2; p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0009] In certain aspects, the disclosure provides a pharmaceutical composition comprising a pharma- ceutically acceptable excipient and a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b).

[0010] In certain aspects, the disclosure provides a method of modulating IL-17A in a subject in need thereof, comprising administering to the subject a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b), or a pharmaceutical composition thereof.

[0011] In certain aspects, the disclosure provides a method of treating an inflammatory disease or condition, comprising administering to a subject a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b), or a pharmaceutical composition thereof. In some embodiments, the inflammatory disease or condition is selected from plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis.

[0012] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be used in carrying out the invention. The following claims define the scope of the invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0014] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications cited herein are incorporated by reference.

[0015] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0016] "Alkyl" refers to the monovalent radical of a linear or branched hydrocarbon chain, consisting solely of carbon and hydrogen atoms, containing no unsaturation, preferably having one to twelve carbon atoms (i.e., C 1 -C 12 Alkyl is attached to the remainder of the molecule via a single bond. In certain embodiments, alkyl contains 1 to 12 carbon atoms (i.e., C 1 ~C 12In certain embodiments, alkyl contains 1 to 8 carbon atoms (i.e., C 1 ~C 8 In other embodiments, alkyl contains 1 to 5 carbon atoms (i.e., C 1 ~C 5 In other embodiments, alkyl contains 1 to 4 carbon atoms (i.e., C 1 ~C 4 In other embodiments, alkyl contains 1 to 3 carbon atoms (i.e., C 1 ~C 3 In other embodiments, alkyl contains 1 to 2 carbon atoms (i.e., C 1 ~C 2 In other embodiments, an alkyl group contains one carbon atom (i.e., C 1 In other embodiments, the alkyl group contains 5 to 15 carbon atoms (i.e., C 5 ~C 15 In other embodiments, the alkyl group contains 5 to 8 carbon atoms (i.e., C 5 ~C 8 In other embodiments, the alkyl group contains 2 to 5 carbon atoms (i.e., C 2 ~C 5 In other embodiments, the alkyl group contains 3 to 5 carbon atoms (i.e., C 3 ~C 5 For example, an alkyl group can be attached to the remainder of the molecule by a single bond, such as methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl), and the like.

[0017] "Alkenyl" refers to a linear or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms (i.e., C 2 ~C 12alkenyl). In certain embodiments, alkenyl contains 2 to 8 carbon atoms (i.e., C 2 ~C 8 alkenyl). In certain embodiments, alkenyl contains 2 to 6 carbon atoms (i.e., C 2 ~C 6 In other embodiments, the alkenyl contains 2 to 4 carbon atoms (i.e., C 2 ~C 4 Alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like.

[0018] "Alkynyl" refers to a linear or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms (i.e., C 2 ~C 12 In certain embodiments, alkynyl contains 2 to 8 carbon atoms (i.e., C 2 ~C 8 In other embodiments, alkynyl contains 2 to 6 carbon atoms (i.e., C 2 ~C 6 In other embodiments, alkynyl contains 2 to 4 carbon atoms (i.e., C 2 ~C 4 Alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0019] "Alkylene" refers to a linear divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and preferably having 1 to 12 carbon atoms, e.g., methylene, ethylene, propylene, butylene, etc. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through the terminal carbons, respectively. The alkylene chain may be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, an alkylene contains 1 to 10 carbon atoms (i.e., C 1 ~C 10 In certain embodiments, the alkylene contains 1 to 8 carbon atoms (i.e., C 1 ~C 8 In other embodiments, the alkylene contains 1 to 5 carbon atoms (i.e., C 1 ~C 5 In other embodiments, the alkylene contains 1 to 4 carbon atoms (i.e., C 1 ~C 4 In other embodiments, the alkylene contains 1 to 3 carbon atoms (i.e., C 1 ~C 3 In other embodiments, the alkylene contains 1 to 2 carbon atoms (i.e., C 1 ~C 2 In other embodiments, the alkylene contains one carbon atom (i.e., C 1 In other embodiments, the alkylene contains 5 to 8 carbon atoms (i.e., C 5 ~C 8 In other embodiments, the alkylene contains 2 to 5 carbon atoms (i.e., C 2 ~C 5 In other embodiments, the alkylene contains 3 to 5 carbon atoms (i.e., C 3 ~C 5 alkylene).

[0020] "Alkenylene" refers to a linear divalent hydrocarbon chain, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group are through the terminal carbons, respectively. The alkenylene chain may be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, an alkenylene contains 2 to 10 carbon atoms (i.e., C 2 ~C 10 In certain embodiments, the alkenylene contains 2 to 8 carbon atoms (i.e., C 2 ~C 8 In other embodiments, the alkenylene contains 2 to 5 carbon atoms (i.e., C 2 ~C 5 In other embodiments, the alkenylene contains 2 to 4 carbon atoms (i.e., C 2 ~C 4 In other embodiments, the alkenylene contains 2 to 3 carbon atoms (i.e., C 2 ~C 3 In other embodiments, the alkenylene contains two carbon atoms (i.e., C 2 In other embodiments, the alkenylene contains 5 to 8 carbon atoms (i.e., C 5 ~C 8 In other embodiments, the alkenylene contains 3 to 5 carbon atoms (i.e., C 3 ~C 5 alkenylene).

[0021] "Alkenylene" refers to a linear divalent hydrocarbon chain, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group are through the terminal carbons, respectively. The alkynylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, an alkynylene contains 2 to 10 carbon atoms (i.e., C 2 ~C 10 In certain embodiments, the alkynylene contains 2 to 8 carbon atoms (i.e., C 2 ~C 8 In other embodiments, the alkynylene contains 2 to 5 carbon atoms (i.e., C 2 ~C 5 In other embodiments, the alkynylene contains 2 to 4 carbon atoms (i.e., C 2 ~C 4 In other embodiments, the alkynylene contains 2 to 3 carbon atoms (i.e., C 2 ~C 3 In other embodiments, the alkynylene contains two carbon atoms (i.e., C 2 In other embodiments, the alkynylene contains 5 to 8 carbon atoms (i.e., C 5 ~C 8 In other embodiments, the alkynylene contains 3 to 5 carbon atoms (i.e., C 3 ~C 5 alkynylene).

[0022] "C x-y The term "alkyl," when used in conjunction with a chemical moiety such as alkyl, alkenyl, or alkynyl, is meant to include groups containing x to y carbons in the chain. For example, "C 1~6 The term "alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups, containing from 1 to 6 carbons.x-y The term alkylene refers to a substituted or unsubstituted alkylene chain having x to y carbons in the alkylene chain. For example, C 1~6 Alkylene may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.

[0023] "C x-y Alkenyl" and "C x-y The term "alkynyl" refers to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively. x-y The term alkenylene refers to a substituted or unsubstituted alkenylene chain having x to y carbons in the alkenylene chain. For example, C 2~6 Alkenylene may be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. The alkenylene chain may have one double bond or two or more double bonds in the alkenylene chain. x-y The term alkynylene refers to a substituted or unsubstituted alkynylene chain having x to y carbons in the alkynylene chain. For example, C 2~6 Alkynylene can be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. The alkynylene chain can have one triple bond or two or more triple bonds within the alkynylene chain.

[0024] The term "carbocycle" as used herein refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocycles include 3-10 membered monocyclic rings and 6-12 membered bicyclic rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. A bicyclic carbocycle may be a fused, bridged, or spiro ring system. In some embodiments, a carbocycle is an aryl. In some embodiments, a carbocycle is a cycloalkyl. In some embodiments, a carbocycle is a cycloalkenyl. In exemplary embodiments, an aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of carbocycle, valences permitting. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Carbocycles may be optionally substituted with one or more substituents such as those described herein.

[0025] "Cycloalkyl" refers to a stable fully saturated monocyclic or polycyclic hydrocarbon radical, consisting solely of carbon and hydrogen atoms, including fused or bridged ring systems, preferably having from 3 to 12 carbon atoms (i.e., C 3~12 In certain embodiments, cycloalkyl contains 3 to 10 carbon atoms (i.e., C 3ー10 In other embodiments, cycloalkyl contains 5 to 7 carbon atoms (i.e., C 5ー7 Cycloalkyl). A cycloalkyl may be attached to the remainder of the molecule by a single bond. Examples of monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. A cycloalkyl may be optionally substituted by one or more substituents, such as those described herein.

[0026] "Cycloalkenyl" refers to a stable unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical, consisting solely of carbon and hydrogen atoms, preferably having from 3 to 12 carbon atoms and including fused or bridged ring systems containing at least one double bond (i.e., C 3~12 In certain embodiments, a cycloalkenyl contains 3 to 10 carbon atoms (i.e., C 3~10 In other embodiments, the cycloalkenyl contains 5 to 7 carbon atoms (i.e., C 5~7 Cycloalkenyl). The cycloalkenyl may be attached to the remainder of the molecule by a single bond. Examples of monocyclic cycloalkenyl include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. The cycloalkenyl may be optionally substituted by one or more substituents, such as those described herein.

[0027] "Aryl" refers to a radical derived from an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. An aromatic monocyclic or aromatic polycyclic hydrocarbon ring system contains only hydrogen and carbon and 5 to 18 carbon atoms, and at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic delocalized (4n+2) π-electron system according to the Hückel theory. Ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. An aryl may be optionally substituted by one or more substituents, such as those described herein.

[0028] "C x-y "Carbocyclic" is meant to include groups containing x to y carbons in the ring. For example, "C 3~6 The term "carbocycle" may refer to a saturated, unsaturated, or aromatic ring system containing from 3 to 6 carbon atoms, any of which may be optionally substituted as provided herein.

[0029] The term "heterocycle" as used herein refers to a saturated, unsaturated, non-aromatic, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3-10 membered monocyclic rings and 6-12 membered bicyclic rings. Each ring of a bicyclic heterocycle can be selected from saturated, unsaturated, and aromatic rings. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. A heterocycle may be attached to the remainder of the molecule through any atom of the heterocycle where a valence allows, such as a carbon or nitrogen atom of the heterocycle. In some embodiments, a heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl. The heterocycle can be optionally substituted with one or more substituents, such as those described herein. Bicyclic heterocycles can be fused, bridged, or spiro ring systems. In exemplary embodiments, the heterocycle, such as pyridyl, can be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. The heterocycle can be optionally substituted with one or more substituents, such as those described herein.

[0030] "Heterocycloalkyl" refers to a stable 3- to 12-membered non-aromatic ring radical containing 2-12 carbon atoms and at least one heteroatom, each of which may be selected from N, O, Si, P, B, and S atoms. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. A heterocycloalkyl may be selected from monocyclic or bicyclic, and fused or bridged ring systems. The heteroatoms in a heteroaryl radical are optionally oxidized. If present, one or more nitrogen atoms are optionally quaternized. A heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl is attached to the remainder of the molecule through any atom of the heterocycloalkyl where a valence allows, such as any carbon or nitrogen atom of the heterocycloalkyl. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Heterocycloalkyls may be optionally substituted with one or more substituents, such as those described herein.

[0031] The term "heteroaryl" refers to a radical derived from a 3-12 membered aromatic ring radical containing 1-11 carbon atoms and at least one heteroatom, each of which may be selected from N, O, and S. In some embodiments, the heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heteroaryl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heteroaryl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. As used herein, heteroaryl rings may be selected from monocyclic or bicyclic and fused or bridged ring systems, where at least one of the rings in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2) π-electron system according to the Hückel theory. The heteroatoms in the heteroaryl radical may be optionally oxidized. If present, one or more nitrogen atoms are optionally quaternized. Heteroaryls may be attached to the remainder of the molecule through any atom of the heteroaryl where valence allows, such as a carbon or nitrogen atom of the heteroaryl. Heteroaryls include aromatic monocyclic structures, preferably 5-6 membered rings, whose ring structures include at least one heteroatom, preferably 1-4 heteroatoms, more preferably 1 or 2 heteroatoms. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. Heteroaryls may be optionally substituted with one or more substituents, such as those described herein. Heteroaryls also include polycyclic ring systems having two or more rings in which two or more atoms are common to two adjacent rings, where at least one of the rings is heteroaromatic, and the other ring may be, for example, aromatic or non-aromatic carbocyclic, or heterocyclic. Heteroaryls may be optionally substituted with one or more substituents, such as those described herein.

[0032] An "X-membered heterocycle" refers to the number of ring atoms in the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 ring atoms, e.g., triazole, oxazole, thiophene, and the like.

[0033] "Alkoxy" refers to a radical attached through an oxygen atom of the formula --O-alkyl, where alkyl is an alkyl chain as defined above.

[0034] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents.

[0035] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl radical, as defined above, that is substituted with one or more halogen radicals, such as, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl radical is optionally further substituted. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di- and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of an alkane (or substituted alkane) and a halogen (e.g., Cl, Br, F, and I). When an alkyl group is substituted with two or more halogen radicals, each halogen can be independently selected from, for example, 1-chloro, 2-fluoroethane.

[0036] The term "substituted" refers to the substitution of one or more carbon or hydrogen on a substitutable heteroatom, e.g., NH or NH of a compound. 2"Substituted" or "substituted with" will be understood to include the implicit proviso that such substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, and the like, subject to the allowed valences of the substituted atom and substituent. In certain embodiments, substituted refers to a moiety having a substituent replacing two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon with an oxo, imino, or thioxo group. As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In a broad respect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds.

[0037] In some embodiments, a substituent may be any of the substituents described herein, for example, halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO 2 ), imino (=NH), oximo (=N-OH), hydrazine (=N-NH 2 ), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a ) 2 , -R b -N(R a ) 2 , -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a ) 2 , -R b -OR c -C(O)N(R a ) 2 , -R b -N(Ra )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a ) 2 (t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may be alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO 2 ), imino (=NH), oximo (=N-OH), hydrazine (=N-NNH 2 ), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a ) 2 , -R b -N(R a ) 2 , -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a ) 2 , -R b -OR c -C(O)N(Ra ) 2 , -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a ) 2 (t is 1 or 2), a is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, where valences permit; a is alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO 2 ), imino (=NH), oximo (=N-OH), hydrazine (=NNH 2 ), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a ) 2 , -R b -N(R a ) 2 , -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(Ra ) 2 , -R b -OR c -C(O)N(R a ) 2 , -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a ) 2 (t is 1 or 2), and each R b is independently selected from a direct bond or a linear or branched alkylene chain, alkenylene chain, or alkynylene chain; each R c is a straight or branched alkylene, alkenylene or alkynylene chain. It will be understood by those skilled in the art that the substituents themselves can be substituted, where appropriate.

[0038] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Pharmaceutically acceptable base addition salts can be formed with inorganic and / or organic bases.

[0039] 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 without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0040] The phrase "pharmaceutically acceptable excipient" or "pharmaceutically acceptable carrier" as used herein means a pharma- ceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the patient.

[0041] The terms "subject," "individual," and "patient" may be used interchangeably and refer to humans, as well as non-human mammals (e.g., non-human primates, dogs, horses, cats, pigs, cows, ungulates, rabbits, etc.). In various embodiments, a subject may be a human (e.g., an adult male, adult female, adolescent male, adolescent female, boy, girl) under the care of a physician or other patient in a hospital, as an outpatient medical practitioner, or in other clinical settings. In certain embodiments, a subject may not be under the care or prescription of a physician or other medical practitioner.

[0042] As used herein, the phrase "a subject in need thereof" refers to a subject as described herein suffering from or at risk of a condition to be treated prophylactically or therapeutically with a compound or salt as described herein.

[0043] The terms "administer", "administered", "administering" and "administering" are defined as providing a composition to a subject via a route known in the art, including, but not limited to, intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In certain embodiments, the oral route of administering the composition can be used. The terms "administer", "administered", "administers", and "administering" a compound should be understood to mean providing a compound of the invention or a prodrug of a compound of the invention to an individual in need.

[0044] As used herein, "treatment" or "treating" refers to an approach to obtain beneficial or desired results, including but not limited to therapeutic benefit and / or preventive benefit, with respect to a disease, disorder, or medical condition. In certain embodiments, treating or treating involves administering a compound or composition disclosed herein to a subject. Therapeutic benefit may include eradication or amelioration of the underlying disease being treated. Therapeutic benefit may also be achieved by eradication or amelioration of one or more of the physiological symptoms associated with the underlying disease, such as observing an improvement in a subject, even though the subject may still be suffering from the underlying disease. In certain embodiments, for preventive benefit, the composition is administered to a subject at risk of developing a particular disease or to a subject reporting one or more of the physiological symptoms of a disease, even if a diagnosis of the disease has not been made. Treating may include, for example, reducing, delaying, or alleviating the severity of one or more symptoms of a disease or condition, or reducing the frequency with which a symptom, such as a disease, defect, disorder, or adverse condition, is experienced by a patient. Treating can be used herein to refer to a method that results in some level of cure or improvement of a disease or condition, and can contemplate a range of outcomes directed to that end, including, but not limited to, complete prevention of the condition.

[0045] In certain embodiments, the term "prevent" or "preventing" in relation to a disease or disorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in a treated sample compared to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition compared to an untreated control sample.

[0046] A "therapeutic effect," as that term is used herein, encompasses the therapeutic and / or prophylactic benefits described above. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0047] compound Lactam-substituted 6-imidazopyridazine IL-17A modulators In some aspects, the present disclosure provides a compound of formula (I):

[0048] [ka] or a pharma- ceutically acceptable salt thereof, wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; Halogen, -OR11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -N(R 12 )S(O) 2 R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN; C 1~10 Alkyl and C 3~10 Carbocyclic rings, each of which is halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, C 3~10 and optionally substituted with one or more substituents independently selected from a carbocyclic ring and a 3- to 10-membered heterocyclic ring, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -NO 2 , =O, =N(R 12 ), and -CN, 1~10 Alkyl and C 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from Each R 5 shall, for each occurrence, consist of (i), (ii), and (iii) of the following: (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2R 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; and (iii) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN; and Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13)C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; are independently selected from Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), -CN; and halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; or The Two R's 1 The substituents, taken together, are C 3~6 can form a carbocyclic ring, C 3~6 The carbocycle is Halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A )2 , -NO 2 , =O, =S, =N(R 18A ), -CN; and halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , =O, =S, =N(R 18A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 and optionally substituted with one or more substituents independently selected from alkyl, R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN.1~6 alkyl, Each R 3 is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 independently selected from alkyl, Each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17A )C(O)R 17A , -N(R17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 independently selected from alkyl, R 11 , R 11A , R 12 , R 13 , R 14 , R 14A , R 15 , R 16 , R 17 , R 17A , and R 18A For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2; m is selected from 0, 1, and 2; p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0049] In some embodiments, for a compound or salt of formula (I), R 1 is replaced by C 3~10 In some embodiments, R 1 is replaced by C 3~10 In some embodiments, R 1 is replaced by C 3~10 In some embodiments, R 1 is replaced by C 3 Carbocyclic, optionally substituted C 4 Carbocyclic, optionally substituted C 5 Carbocyclic, optionally substituted C 6 Carbocyclic, optionally substituted C 7 Carbocyclic, optionally substituted C 8 Carbocyclic, optionally substituted C 9 Carbocyclic and optionally substituted C 10 In some embodiments, R 1 is replaced by C 3~4 Carbocyclic, optionally substituted C 3~5 Carbocyclic, optionally substituted C 3~6 Carbocyclic, optionally substituted C 3~7 Carbocyclic, optionally substituted C3~8 Carbocyclic, optionally substituted C 3~9 Carbocyclic and optionally substituted C 3~10 In some embodiments, R 1 is replaced by C 3~10 and the optional substituents are as defined herein. In some embodiments, R 1 is replaced by C 3~10 It is a carbocyclic ring, and the optional substituents are as defined in formula (I), (II), (II-a), or (II-b).

[0050] In some embodiments, for a compound or salt of formula (I), R 1 is halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), -CN; and halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic ring, R 14A is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 It is selected from a carbocycle and a 3- to 6-membered heterocycle.

[0051] In some embodiments, for a compound or salt of formula (I), R 1 is halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), -CN; and halogen, -OR 14A , -SR 14A , -N(R 14A ) 2 , -C(O)R 14A , -C(O)N(R 14A ) 2 , -N(R 14A )C(O)R 14A , -C(O)OR 14A , -OC(O)R 14A , -S(O)R 14A , -S(O) 2 R 14A , -NO 2 , =O, =S, =N(R 14A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 In some embodiments, R 1 is halogen, -OR 14A , -N(R 14A) 2 , -C(O)R 14A , -NO 2 , -CN; and halogen, -OR 14A , -N(R 14A ) 2 , -C(O)R 14A , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 C optionally substituted with one or more substituents independently selected from alkyl 3~6 In some embodiments, R 1 is halogen, -OR 14A , -N(R 14A ) 2 , -C(O)R 14A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 In some embodiments, R 1 teeth,

[0052] [ka] It is.

[0053] In some embodiments, for a compound or salt of formula (I), two R 1 The substituents, taken together, are C 3~6 can form a carbocyclic ring, C 3~6 The carbocyclic ring is halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , =O, =S, =N(R 18A ), -CN; and halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO2 , =O, =S, =N(R 18A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 and optionally substituted with one or more substituents independently selected from alkyl, R 18A is hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl.

[0054] In some embodiments, for a compound or salt of formula (I), two R 1 The substituents, taken together, are C 3~6 can form a carbocyclic ring, C 3~6 The carbocyclic ring is halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , =O, =S, =N(R 18A ), -CN; and halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , =O, =S, =N(R 18A ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 In some embodiments, two R 1 The substituents, taken together, are halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6In some embodiments, two R on the same carbon atom can form a cycloalkyl. 1 The substituents, taken together, are halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 cycloalkyl (e.g., two R 1 The substituents, taken together, are C 3 can form a cycloalkyl,

[0055] [ka] teeth,

[0056] [ka] In some embodiments, two R on adjacent carbon atoms are 1 The substituents, taken together, are halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 cycloalkyl (e.g., two R 1 The substituents, taken together, are C 3 Forming a cycloalkyl,

[0057] [ka] teeth,

[0058] [ka] In some embodiments, two R 1 The substituents, taken together, are halogen, -OR 18A , -N(R 18A ) 2 , -C(O)R 18A , -C(O)N(R 18A ) 2 , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 A cycloalkyl group (e.g., two R 1 The substituents, taken together, are C 4 Forming a cycloalkyl,

[0059] [ka] teeth,

[0060] [ka] In some embodiments, two R 1 The substituents, taken together,

[0061] [ka] may be formed.

[0062] In some embodiments, for a compound or salt of formula (I), R 4 is -N(R 17A )C(O)R 17A And each R 17A is hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl.

[0063] In some embodiments, for the compound or salt of Formula (I), A is a 5-6 membered heteroaryl, any of which is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0064] In some embodiments, for the compound or salt of Formula (I), A is a 5-6 membered heteroaryl, any of which is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0065] In some embodiments, for the compound or salt of Formula (I), A is a 5-6 membered heteroaryl, any of which is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A, -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0066] In some embodiments, for the compound or salt of Formula (I), A is a 5-6 membered heteroaryl, any of which is Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 carbocycle, optionally substituted with one or more substituents independently selected from:

[0067] In some embodiments, for the compound or salt of formula (I), A is Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 and carbocycle is a 5-membered heteroaryl optionally substituted with one or more substituents independently selected from:

[0068] In some embodiments, for the compound or salt of formula (I), A is halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 In some embodiments, A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and oxadiazolyl, optionally substituted with a carbocyclic ring. 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 It is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, optionally substituted with a saturated carbocyclic ring.

[0069] In some embodiments, for the compound or salt of formula (I), A is halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 In some embodiments, A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, optionally substituted with cycloalkyl. In some embodiments, A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, optionally substituted with cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, each of which is selected from halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R11A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 In some embodiments, A is optionally substituted with one or more substituents independently selected from haloalkyl.

[0070] [ka] In some embodiments, A is selected from:

[0071] [ka] In some embodiments, A is selected from:

[0072] [ka] In some embodiments,

[0073] [ka]

[0074] In some embodiments, for a compound or salt of formula (I), R 11A , R 14A , R 17A , and R 18A are, respectively, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 It is selected from a carbocycle and a 3- to 10-membered heterocycle.

[0075] In some aspects, the present disclosure provides a compound represented by the structure of formula (II):

[0076] [ka] or a pharma- ceutically acceptable salt thereof, wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11)C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and optionally substituted with one or more substituents independently selected from B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -N(R 12 )S(O) 2 R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R12 , -NO 2 , =O, =S, =N(R 12 ), -CN; C 1~10 Alkyl and C 3~10 carbocyclic rings, each of which is independently halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, C 3~10 is optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle; 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -NO 2 , =O, =N(R 12 ), and -CN, 1~10 Alkyl and C 3~10 and optionally substituted with one or more substituents independently selected from carbocycles; Each R 5 shall, for each occurrence, consist of (i), (ii), and (iii) of the following: (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; and (iii) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R13 , -NO 2 , =O, =S, =N(R 13 ), -CN; and Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; are independently selected from Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), -CN; and Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; are independently selected from R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN; and Halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; is selected from Each R 3 For each occurrence, Hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN; and Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; or Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN; and Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; are independently selected from R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2; m is selected from 0, 1, and 2; p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0077] In some embodiments, for a compound or salt of Formula (II), n is 1.

[0078] In some embodiments, formula (II) is represented by the structure of formula (II-a):

[0079] [ka]

[0080] In some embodiments, formula (II) is represented by the structure of formula (II-a):

[0081] [ka] In the formula, R 1 , R 2 , R 3 , R 4 , A, B, p and m are each defined as in formula (I).

[0082] In some embodiments, formula (II) is represented by the structure of formula (II-a):

[0083] [ka] In the formula, R 1 , R 2 , R 3 , R 4 , A, B, p and m are each defined as in formula (II).

[0084] In some embodiments, for a compound or salt of Formula (II), n is 2.

[0085] In some embodiments, formula (II) is represented by the structure of formula (II-b):

[0086] [ka]

[0087] In some embodiments, formula (II) is represented by the structure of formula (II-b):

[0088] [ka] In the formula, R 1 , R 2 , R 3 , R 4 , A, B, p and m are each defined as in formula (I).

[0089] In some embodiments, formula (II) is represented by the structure of formula (II-b):

[0090] [ka] In the formula, R 1 , R 2 , R 3 , R 4 , A, B, p and m are each defined as in formula (II).

[0091] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), p is selected from 0, 1, 2, 3, 4, 5, and 6. In some embodiments, p is selected from 1, 2, 3, 4, 5, and 6. In some embodiments, p is selected from 0, 1, 2, 3, 4, and 5. In some embodiments, p is selected from 0, 1, 2, 3, and 4. In some embodiments, p is selected from 0, 1, 2, and 3. In some embodiments, p is selected from 0, 1, and 2. In some embodiments, p is selected from 0 and 1. In some embodiments, p is selected from 1, 2, 3, 4, and 5. In some embodiments, p is selected from 2, 3, 4, and 5. In some embodiments, p is selected from 3, 4, and 5. In some embodiments, p is selected from 4 and 5. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is 6.

[0092] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), each R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2, =O, =S, =N(R 14 ), -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and -CN, 1~6 In some embodiments, each R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 In some embodiments, each R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14, -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 1 is halogen, -OR 14 , -N(R 14 ) 2 , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 In some embodiments, each R 1 is halogen and -CF 3 In some embodiments, each R 1 -CF 3 It is.

[0093] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), each R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and -CN, 1~6 In some embodiments, R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -NO 2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -NO 2 , -CN, optionally substituted with one or more substituents independently selected from 1~6 In some embodiments, each R 1 For each occurrence, halogen, C 1~6 Alkyl, and C 1~6 In some embodiments, each R 1 Each occurrence represents methyl, ethyl,

[0094] [ka] is selected from.

[0095] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15, -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN, and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 In some embodiments, R 2is halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, R 2 is hydrogen, halogen, -OR 15 , -N(R 15 ) 2 , -C(O)R 15 , -NO 2 , -CN,C 1~3 Alkyl, and C 1~3 In some embodiments, R is selected from haloalkyl. 2 is hydrogen, halogen, and C 1~3 In some embodiments, R 2 is selected from hydrogen, halogen, methyl, and ethyl. 2 is hydrogen.

[0096] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), R 2 is hydrogen, C 1~3 Alkyl and C 1~3 haloalkyl.

[0097] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), each R 3 is hydrogen, halogen, -OR 16 , -SR 16 , -N(R16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN, and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , and -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 3 is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16, -NO 2 In some embodiments, each R 3 For each occurrence, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , and -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 In some embodiments, each R 3 Each occurrence represents hydrogen, as well as the halogens, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , and -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 3 is hydrogen, halogen, -OR 16 , -N(R 16 ) 2 , -NO 2 , -CN,C 1~3 Alkyl, and C 1~3 In some embodiments, each R 3Each occurrence of R is independently selected from hydrogen and methyl. 3 is hydrogen.

[0098] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), R 3 Each occurrence represents hydrogen, methyl, ethyl, and

[0099] [ka] are independently selected from

[0100] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), m is 2.

[0101] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), m is 1.

[0102] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), m is 0.

[0103] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO2 , -CN, and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , =O, =S, =N(R 17 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 In some embodiments, each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -C(O)OR 17 , -OC(O)R 17, -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , =O, =S, =N(R 17 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 4 is halogen, -OR 17 , -N(R 17 ) 2 , -NO 2 , -CN,C 1~3 Alkyl, and C 1~3 In some embodiments, each R 4 is selected from chloro, fluoro, methyl, ethyl, and -CN.

[0104] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), m is 1 and R 4 is halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 In some embodiments, R 4 is halogen, -OR 17 , -N(R 17 ) 2 , -C(O)R 17 , -S(O) 2 R 17 R is selected from -CN, 17 For each occurrence, hydrogen; halogen; -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , =O, -CN, C 3~6 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 6-membered heterocycles 1~6 Alkyl, each C 3~6 Carbocyclic and 3- to 6-membered heterocyclic rings, C 1~6 Alkyl; halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~6 In some embodiments, R 4 -Cl, -CN,

[0105] [ka] In some embodiments, R 4 is halogen, -OR 17 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 is alkyl, R 17For each occurrence, halogen, C 1~6 Alkyl, and C 1~6 In some embodiments, R is selected from haloalkyl. 4 is methyl,

[0106] [ka] is selected from.

[0107] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), A is optionally substituted C 3~6 In some embodiments, A is an optionally substituted saturated C 3~6 In some embodiments, A is an optionally substituted unsaturated C 3~6 In some embodiments, A is an optionally substituted C 3~5 Carbocyclic, optionally substituted C 3~4 Carbocyclic, optionally substituted C 4~6 Carbocyclic and optionally substituted C 5~6 In some embodiments, A is selected from optionally substituted C 3 Carbocyclic, optionally substituted C 4 Carbocyclic, optionally substituted C 5 Carbocyclic and optionally substituted C 6 carbocycles.

[0108] In some embodiments, for the compounds or salts of formula (I), (II), (II-a), or (II-b), A is an optionally substituted 5-6 membered heteroaryl. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one nitrogen or oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one nitrogen or sulfur heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one sulfur or oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one sulfur heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one nitrogen heteroatom.

[0109] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), A is a saturated C 3~6 carbocycle and 5-membered heteroaryl, both of which are Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~6 Alkyl; and optionally substituted with one or more substituents independently selected from:

[0110] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), A is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~6 and 5-6 membered heteroaryl optionally substituted with one or more substituents independently selected from alkyl.

[0111] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), A is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and -CN, 1~6 and 5-membered heteroaryl optionally substituted with one or more substituents independently selected from alkyl.

[0112] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), A is halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 )2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 In some embodiments, A is a 5-6 membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN,C 3~6 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 6-membered heterocycles 1~6 is a 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from alkyl, 3~6 The carbocyclic ring and the 3- to 6-membered heterocyclic ring are each -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and -CN.

[0113] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), A is 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which may be selected from halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 In some embodiments, A is optionally substituted with one or more substituents independently selected from halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 In some embodiments, A is a 5-6 membered heteroaryl optionally substituted with one or more substituents independently selected from a carbocycle, a halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 and -CN, optionally substituted with one or more substituents selected from 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 The carbocycle is an optionally substituted 5-membered heteroaryl.

[0114] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any one of which is halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, A is selected from pyrazolyl and oxadiazolyl, each of which is selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R11 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with methyl, ethyl, isopropyl, or propyl. In some embodiments, A is

[0115] [ka] In some embodiments, A is selected from:

[0116] [ka] In some embodiments, A is

[0117] [ka] It is.

[0118] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), A is selected from thiophenyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any one of which is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and -CN, 1~6 It is optionally substituted with one or more substituents independently selected from alkyl.

[0119] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), A is selected from thiophenyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, and triazolyl, any one of which is halogen, -OR 11 , -N(R 11 ) 2 , -NO 2 , -CN; and halogen, -OR 11 , -N(R 11 ) 2 , -NO 2 , -CN,C 3~6 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 6-membered heterocycles 1~6In some embodiments, A is selected from thiophenyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, and triazolyl, any one of which is selected from -OR 11 , -N(R 11 ) 2 , -CN; and halogen, -OR 11 , -N(R 11 ) 2 , and C 3~6 C optionally substituted with one or more substituents independently selected from cycloalkyl 1~3 In some embodiments, A is optionally substituted with one or more substituents independently selected from alkyl.

[0120] [ka] is selected from.

[0121] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), A is optionally substituted C 3~6 In some embodiments, the optionally substituted C of A is 3~6 A carbocycle is an optionally substituted C 4~6 Spirocyclic carbocycles and optionally substituted C 4~6 In some embodiments, the optionally substituted C of A is selected from the group consisting of aryl, aryl, aryl and heteroaryl. 4~6 Spirocyclic carbocycles and optionally substituted C 4~6 The optional substituents of the bridged carbocycle are as defined herein. In some embodiments, the optionally substituted C of A 4~6 Spirocyclic carbocycles and optionally substituted C 4~6 The optional substituents of the bridged carbocycle are as defined in formula (II), (II-a), or (II-b).

[0122] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), A is halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN; and halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 C optionally substituted with one or more substituents independently selected from alkyl 3~6 In some embodiments, the optionally substituted C of A is 3~6 Carbocycles are spirocyclic C 4~6 Carbocyclic and bridged C 4~6 carbocyclic rings, each of which is selected from halogen, -OR 11 , -N(R 11 ) 2 -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 In some embodiments, A is optionally substituted with one or more substituents independently selected from haloalkyl.

[0123] [ka] It is.

[0124] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), B is -C(H)(R 5 )2 In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 3~6 In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and one or more substituents C optionally substituted with one or more substituents independently selected from -CN; 1~6 C optionally substituted with alkyl 3~6 carbocycle.

[0125] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), -C(H)(R 5 ) 2 Each R 5 teeth, Halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO2 , -CN; Halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; and Halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~10 carbocycle.

[0126] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), R 5 is replaced by C 3~10 In some embodiments, R 5 is replaced by C 3~4 Carbocyclic, optionally substituted C 3~5 Carbocyclic, optionally substituted C 3~6 Carbocyclic, optionally substituted C 3~7 Carbocyclic, optionally substituted C 3~8 Carbocyclic and optionally substituted C 3~9 In some embodiments, R 5 is replaced by C 4~10 Carbocyclic, optionally substituted C 5~10 Carbocyclic, optionally substituted C 6~10 Carbocyclic, optionally substituted C 7~10 Carbocyclic, optionally substituted C 8~10 Carbocyclic and optionally substituted C 9~10 In some embodiments, R 5is replaced by C 3~10 In some embodiments, R 5 is replaced by C 3~10 In some embodiments, R 5 is replaced by C 3~6 Carbocyclic and optionally substituted C 6~10 In some embodiments, R 5 is replaced by C 3~8 Monocyclic carbocycles and optionally substituted C 6~10 bicyclic carbocycles.

[0127] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), -C(H)(R 5 ) 2 Each R 5 is halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 In some embodiments, -CH(R 5 ) 2 teeth,

[0128] [ka] It is.

[0129] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), -C(H)(R 5 ) 2 Each R 5 is halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), and -CN; and halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~10 C optionally substituted with one or more substituents independently selected from carbocycles 1~6 In some embodiments, —C(H)(R 5 ) 2 Each R 5 is halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), and -CN. In some embodiments, -CH(R 5 ) 2 teeth,

[0130] [ka] In some embodiments, B is selected from:

[0131] [ka] In some embodiments, B is selected from:

[0132] [ka] In some embodiments, B is

[0133] [ka] It is.

[0134] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), B is optionally substituted C 3~10 In some embodiments, B is an optionally substituted C 3~4 Carbocyclic, optionally substituted C 3~5 Carbocyclic, optionally substituted C 3~6 Carbocyclic, optionally substituted C 3~7 Carbocyclic, optionally substituted C 3~8 Carbocyclic and optionally substituted C 3~9 In some embodiments, B is selected from optionally substituted C 4~10 Carbocyclic, optionally substituted C 5~10 Carbocyclic, optionally substituted C 6~10 Carbocyclic, optionally substituted C 7~10 Carbocyclic, optionally substituted C 8~10 Carbocyclic and optionally substituted C 9~10 In some embodiments, B is selected from optionally substituted C 3~10 In some embodiments, B is an optionally substituted C 3~10 In some embodiments, B is an optionally substituted C 3~6 Carbocyclic and optionally substituted C 6~10 In some embodiments, B is selected from optionally substituted C 3~8 Monocyclic carbocycles and optionally substituted C 6~10 bicyclic carbocycles.

[0135] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), B is a halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12), -CN; and halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 C optionally substituted with one or more substituents independently selected from alkyl 6~10 In some embodiments, B is a halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and C optionally substituted with one or more substituents independently selected from -CN. 6~10 In some embodiments, B is a halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and one or more C optionally substituted with one or more substituents independently selected from -CN. 1~6 C optionally substituted with alkyl 6~10 It is a carbocyclic ring.

[0136] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), B is selected from cyclohexyl and cycloheptyl, each of which is selected from halogen, -OR 12 , N(R 12 ) 2 , -NO 2 , -CN, and halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6In some embodiments, B is selected from cyclohexyl and cycloheptyl, each of which is optionally substituted with one or more substituents independently selected from halogen, C 1~6 Alkyl, and C 1~6 In some embodiments, B is optionally substituted with one or more substituents independently selected from haloalkyl.

[0137] [ka] In some embodiments, B is selected from:

[0138] [ka] In some embodiments, B is selected from:

[0139] [ka] In some embodiments, B is

[0140] [ka] In some embodiments, B is

[0141] [ka] In some embodiments, B is

[0142] [ka] In some embodiments, B is

[0143] [ka] It is.

[0144] In some embodiments, for the compound or salt of formula (I), (II), (II-a), or (II-b), B is a monocyclic C 3~7 Carbocyclic and bicyclic C 5~10 carbocyclic rings, each of which is selected from halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN; and C 1~6 Alkyl and C 3~10 carbocyclic rings, each of which is selected from the group consisting of halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and -CN, 1~6 Alkyl and C 3~10 In some embodiments, B is optionally substituted with one or more substituents independently selected from halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, C 1~6 Alkyl, C 1~6 Haloalkyl and C 3~6 A monocyclic C optionally substituted with one or more substituents independently selected from cycloalkyl 3~7 In some embodiments, B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, any of which is selected from halogen, C 1~6 Alkyl, C 1ー6 Haloalkyl and C 3~6 In some embodiments, B is optionally substituted with one or more substituents independently selected from:

[0145] [ka] is selected from.

[0146] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), B is an optionally substituted bicyclic C 5~10 In some embodiments, B is selected from an optionally substituted fused C 5~10 Carbocyclic, optionally substituted bridge C 5~10 Carbocyclic and optionally substituted spirocyclic C 5~10 In some embodiments, B is selected from an optionally substituted fused C 5~10 In some embodiments, B is an optionally substituted bridge C 5~10 In some embodiments, B is an optionally substituted spirocyclic ring C 5~10 In some embodiments, the fused C 5~10 carbocyclic, bridged C 5~10 Carbocyclic and spirocyclic C 5~10 The optional substituents of the carbocycle are as defined herein. In some embodiments, the fused C 5~10 carbocyclic, bridged C 5~10 Carbocyclic and spirocyclic C 5~10 The optional substituents on the carbocycle are as defined in formula (I).

[0147] In some embodiments, for a compound or salt of formula (I), (II), (II-a), or (II-b), B is a halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, C 1~6 Alkyl, and C 1~6 A bicyclic C optionally substituted with one or more substituents independently selected from haloalkyl 5~10 In some embodiments, the bicyclic C of B is selected from carbocyclic rings. 5~10 A carbocyclic ring is a fused C 5~10 carbocyclic, bridged C 5~10Carbocyclic and spirocyclic C 5~10 carbocyclic rings, any of which may be selected from halogen, C 1~6 Alkyl, and C 1~6 In some embodiments, the bicyclic C of B is optionally substituted with one or more substituents independently selected from haloalkyl. 5~10 Carbocycles are halogens, C 1~6 Alkyl, and C 1~6 Optionally substituted with one or more substituents independently selected from haloalkyl 5~10 In some embodiments, B is selected from

[0148] [ka] In some embodiments, the bicyclic C 5~10 Carbocycles are halogens, C 1~6 Alkyl, and C 1~6 Bridge C optionally substituted with one or more substituents independently selected from haloalkyl 5~10 In some embodiments, B is selected from

[0149] [ka] In some embodiments, the bicyclic C 5~10 Carbocycles are halogens, C 1~6 Alkyl, C 1~6 A spirocyclic C optionally substituted with one or more substituents independently selected from haloalkyl 5~10 In some embodiments, B is selected from

[0150] [ka] is selected from.

[0151] In some embodiments, for a compound or salt of Formula (I), (II), (II-a), or (II-b), R 11 , R 12 , R13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , =O, -CN, C 3~6 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 6-membered heterocycles 1~6 Alkyl, each C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings are not subject to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~6 is independently selected from a carbocycle and a 3- to 6-membered heterocycle.

[0152] In certain aspects, the disclosure provides a compound or salt represented by the structure of formula (I): A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 )2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 , -CN; and halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 and -CN, optionally substituted with one or more substituents selected from 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 A is optionally substituted with one or more substituents independently selected from carbocycles, e.g., A is 3~10 is a 5-membered heteroaryl optionally substituted with a carbocycle; B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R12 , -C(O)OR 12 , -NO 2 , -CN; C 1~10 Alkyl and C 3~10 carbocyclic rings, each of which is independently halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 , -CN,C 3~10 is optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle; 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 and -CN, 1~10 Alkyl and C 3~10 Optionally substituted with one or more substituents independently selected from carbocycles, e.g., B is optionally substituted with C 3~10 is a carbocyclic ring, Each R 5 is, for each occurrence, independently selected from the following: (i), (ii), and (iii): (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN.1~10 Alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN, and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic rings, For example, each R 5 is replaced by C 3~10 Carbocyclic or optionally substituted C 1~10 is alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 carbocyclic ring, e.g., each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, for example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, e.g., each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 alkyl, e.g., each R 4 is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 11A , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0153] In certain aspects, the disclosure provides a compound or salt represented by the structure of formula (I): A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11, -C(O)OR 11 , -NO 2 and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 , -CN; and halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 and -CN, optionally substituted with one or more substituents selected from 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from 3~10 is a 5-membered heteroaryl optionally substituted with a carbocycle; B is -C(H)(R 5 ) 2 And each R 5 shall, for each occurrence, consist of (i), (ii), and (iii) of the following: (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; For example, each R 5 is replaced by C 3~10 Carbocyclic or optionally substituted C 1~10 alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2, -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; For example, each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 , -CN; and Halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; For example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R16 , -C(O)OR 16 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; For example, each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; For example, each R 4 is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 11A , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 Carbocyclic and 3- to 10-membered heterocyclic rings; are independently selected from n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0154] In certain aspects, the disclosure provides compounds or salts represented by the structure of formula (I), (II), (II-a), or (II-b), wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 and -CN, 1~10 Alkyl; and optionally substituted with one or more substituents independently selected from 1~10 is a 5-membered heteroaryl optionally substituted with alkyl; B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 , -CN; C 1~10 Alkyl and C 3~10 carbocyclic rings, each of which is independently halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 , -CN,C 3~10 and optionally substituted with one or more substituents independently selected from a carbocyclic ring and a 3- to 10-membered heterocyclic ring, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 and -CN,1~10 Alkyl and C 3~10 carbocyclic ring; optionally substituted with one or more substituents independently selected from, for example, B is optionally substituted C 3~10 is a carbocyclic ring, each R 5 is, each time it appears, the following (i), (ii), and (iii): (i) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , and -CN, and is optionally substituted with one or more substituents independently selected from C 1~10 alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN, and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , and -CN, and is optionally substituted with one or more substituents independently selected from C 1~10 alkyl, and is optionally substituted with one or more substituents independently selected from C 3~10 carbocyclic ring; independently selected from, for example, each R 5 is optionally substituted C 3~10 carbocyclic ring or optionally substituted C 1~10 alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; For example, each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2, -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, for example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, e.g., each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN.1~10 alkyl, e.g., each R 4 is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 Carbocyclic and 3- to 10-membered heterocyclic rings; are independently selected from n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0155] In certain aspects, the disclosure provides compounds or salts represented by the structure of formula (I), (II), (II-a), or (II-b), wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 and -CN, 1~10 Alkyl; For example, A is optionally substituted with one or more substituents independently selected from C 1~10 is a 5-membered heteroaryl optionally substituted with alkyl; B is -C(H)(R 5 ) 2 And each R 5 shall, for each occurrence, consist of (i), (ii), and (iii) of the following: (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; For example, each R 5 is replaced by C 3~10 Carbocyclic or optionally substituted C 1~10 alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; For example, each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, for example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 )2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, e.g., each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 alkyl, e.g., each R 4 is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3-10 membered heterocyclic rings are halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 Carbocyclic and 3- to 10-membered heterocyclic rings; are independently selected from n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0156] In some aspects, the present disclosure provides a method for producing a pharmaceutical composition comprising:

[0157] [ka] The present invention provides a compound of formula (I) selected from:

[0158] In some aspects, the present disclosure provides a method for producing a pharmaceutical composition comprising:

[0159] [ka]

[0160] [ka]

[0161]

change

[0162]

change

[0163]

change

[0164]

change

[0165]

change

[0166]

change

[0167]

change

[0168]

change

[0169]

change

[0170]

change

[0171]

change

[0172] [ka] The present invention provides a compound of formula (I) selected from:

[0173] Lactam-substituted 7-imidazopyridazine IL-17A modulators

[0174] In some aspects, the present disclosure provides a compound represented by the structure of formula (III):

[0175] [ka] or a pharma- ceutically acceptable salt thereof, wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11, -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A, -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -N(R 12 )S(O) 2 R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN; C 1~10 Alkyl and C 3~10 carbocyclic rings, each of which is independently halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12, -NO 2 , =O, =S, =N(R 12 ), -CN, C 3~10 and optionally substituted with one or more substituents independently selected from a carbocyclic ring and a 3- to 10-membered heterocyclic ring, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -NO 2 , =O, =N(R 12 ), and -CN, 1~10 Alkyl and C 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from Each R 5 shall, for each occurrence, consist of (i), (ii), and (iii) of the following: (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; and (iii) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; and Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; are independently selected from Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), -CN; And halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; are independently selected from R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN; and Halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, Each R 3 For each occurrence, Hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16, -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN; and Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; or Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN; and Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 )2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; are independently selected from R 11 , R 11A , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 Carbocyclic and 3- to 10-membered heterocyclic rings; are independently selected from n is selected from 1 and 2; m is selected from 0, 1, and 2; p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0176] In some embodiments, for the compound or salt of formula (III), A is a 5-6 membered heteroaryl and C 3~6 carbocycles, each of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11, -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~6 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0177] In some embodiments, for the compound or salt of formula (III), A is a 5-6 membered heteroaryl and C 3~6 carbocycles, each of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN,1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0178] In some embodiments, for the compound or salt of formula (III), A is a 5-6 membered heteroaryl and C 3~6 carbocycles, each of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~6 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A )2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0179] In some embodiments, for the compound or salt of formula (III), A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which may be selected from halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 In some embodiments, A is optionally substituted with one or more substituents independently selected from 5-6 membered heteroaryl and C 3~6 carbocyclic ring, each of which is independently selected from halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), and C optionally substituted with one or more substituents independently selected from -CN. 3~10 In some embodiments, A is optionally substituted with one or more substituents independently selected from 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which may be selected from halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A )2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and one or more C optionally substituted with one or more substituents selected from -CN; 1~10 C optionally substituted with alkyl 3~10 Carbocycles are optionally substituted with one or more substituents independently selected from the group consisting of aryl, ... and heterocyclic rings.

[0180] In some embodiments, for the compound or salt of Formula (III), A is selected from 5-6 membered heteroaryl; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl,3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0181] In some embodiments, for the compound or salt of Formula (III), A is selected from 5-6 membered heteroaryl; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A, -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0182] In some embodiments, for the compound or salt of Formula (III), A is selected from 5-6 membered heteroaryl; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 Alkyl; and Halogen, -OR11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 C optionally substituted with one or more substituents independently selected from alkyl, 3~10 Carbocyclic; and optionally substituted with one or more substituents independently selected from:

[0183] In some embodiments, for the compound or salt of formula (III), A is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11, -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), and C optionally substituted with one or more substituents independently selected from -CN. 3~10 Carbocyclic; is an optionally substituted 5-6 membered heteroaryl.

[0184] In some embodiments, for the compound or salt of formula (III), A is Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), -CN; and Halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and -CN, 1~10 Alkyl; C optionally substituted with one or more substituents independently selected from 3~10 In some embodiments, A is a 5-6 membered heteroaryl optionally substituted with a carbocycle. 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -S(O)R 11A , -S(O) 2 R 11A , -NO 2 , =O, =S, =N(R 11A ), and C optionally substituted with one or more substituents independently selected from -CN. 3~10 In some embodiments, A is a 5-6 membered heteroaryl optionally substituted with a carbocycle. 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)N(R 11A ) 2 , -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO 2 , =O, =N(R 11A ), and one or more C optionally substituted with one or more substituents selected from -CN; 1~10 C optionally substituted with alkyl 3~10 The carbocyclic ring is an optionally substituted 5-6 membered heteroaryl.

[0185] In some embodiments, for the compound or salt of formula (III), A is halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 and -CN, optionally substituted with one or more substituents selected from 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 In some embodiments, A is a 5-membered heteroaryl optionally substituted with a carbocycle. 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN, optionally substituted with one or more substituents independently selected from 3~10 In some embodiments, A is a 5-membered heteroaryl optionally substituted with a carbocycle. 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 and -CN, optionally substituted with one or more substituents selected from 1~10 C optionally substituted with alkyl 3~10 The carbocycle is an optionally substituted 5-membered heteroaryl.

[0186] In some embodiments, for the compound or salt of formula (III), A is halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN; and halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2and -CN, optionally substituted with one or more substituents selected from 1~6 C optionally substituted with one or more substituents independently selected from alkyl 3~6 In some embodiments, A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and oxadiazolyl, each of which is selected from halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 It is optionally substituted with cycloalkyl.

[0187] In some embodiments, for the compound or salt of formula (III), A is oxazolyl, isoxazolyl, oxadiazolyl, each of which is halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 In some embodiments, for the compound or salt of formula (III), A is oxazolyl, isoxazolyl, or oxadiazolyl, each of which is independently selected from the group consisting of halogen, -OR 11A , -N(R 11A ) 2 , -C(O)R 11A , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6In some embodiments, for a compound or salt of formula (III), A is oxazolyl, isoxazolyl, oxadiazolyl, each of which is optionally substituted with cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, each of which is optionally substituted with halogen, -OR 11A -N(R 11A ) 2 , -C(O)R 11A -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 In some embodiments, for a compound or salt of formula (III), A is oxazolyl, isoxazolyl, oxadiazolyl, each of which is substituted with one or more substituents independently selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, any of which is substituted with halogen, -OR 11A -N(R 11A ) 2 , -C(O)R 11A -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 and optionally substituted with one or more substituents independently selected from haloalkyl.

[0188] In some embodiments, for the compound or salt of formula (III), A is

[0189] [ka] In some embodiments, A is selected from:

[0190] [ka] In some embodiments, A is

[0191] [ka] It is.

[0192] In some aspects, the present disclosure provides a compound represented by the structure of formula (IV):

[0193] [ka] or a pharma- ceutically acceptable salt thereof, wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~10 and optionally substituted with one or more substituents independently selected from alkyl, B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -N(R 12 )S(O) 2 R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN; C 1~10 Alkyl and C 3~10 carbocyclic rings, each of which is independently halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2, -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -S(O)R 12 , -S(O) 2 R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, C 3~10 is optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle; 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)N(R 12 ) 2 , -N(R 12 )C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -NO 2 , =O, =N(R 12 ), and -CN, 1~10 Alkyl and C 3~10 and optionally substituted with one or more substituents independently selected from carbocycles; Each R 5 is, for each occurrence, independently selected from the following: (i), (ii), and (iii): (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, optionally substituted with one or more substituents independently selected from 1~10 Alkyl; and (iii) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), -CN; and Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13, -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic; Each R 1 For each occurrence, halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~10 independently selected from alkyl, R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, Each R 3 is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16, -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 independently selected from alkyl, Each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN, optionally substituted with one or more substituents independently selected from 1~10 independently selected from alkyl, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2; m is selected from 0, 1, and 2; p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0194] In some embodiments, for a compound or salt of formula (III) or (IV), n is 2.

[0195] In some embodiments, for a compound or salt of formula (III) or (IV), n is 1.

[0196] In certain embodiments, the structure of formula (IV) is represented by formula (IV-a):

[0197] [ka]

[0198] In certain embodiments, the structure of formula (IV) is represented by formula (IV-a):

[0199] [ka]

[0200] In certain embodiments, the structure of formula (IV) has formula (IV-a):

[0201] [ka] wherein R 1 , R 2 , R 3 , R 4 , A, B, p, and m are each defined as in formula (III).

[0202] In certain embodiments, the structure of formula (IV) has formula (IV-a):

[0203] [ka] wherein R 1 , R 2 , R 3 , R 4, A, B, p and m are each defined as in formula (IV).

[0204] In certain embodiments, the structure of formula (IV) has formula (IV-b):

[0205] [ka] It is represented by:

[0206] In certain embodiments, the structure of formula (IV) has formula (IV-b):

[0207] [ka] wherein R 1 , R 2 , R 3 , R 4 , A, B, p and m are each defined as in formula (III).

[0208] In certain embodiments, the structure of formula (IV) has formula (IV-b):

[0209] [ka] wherein R 1 , R 2 , R 3 , R 4 , A, B, p and m are each defined as in formula (IV).

[0210] In some embodiments, for the compounds or salts of formula (III), (IV), (IV-a), and (IV-b), p is selected from 0, 1, 2, 3, 4, 5, and 6. In some embodiments, p is selected from 1, 2, 3, 4, 5, and 6. In some embodiments, p is selected from 0, 1, 2, 3, 4, and 5. In some embodiments, p is selected from 0, 1, 2, 3, and 4. In some embodiments, p is selected from 0, 1, 2, and 3. In some embodiments, p is selected from 0, 1, and 2. In some embodiments, p is selected from 0 and 1. In some embodiments, p is selected from 1, 2, 3, 4, and 5. In some embodiments, p is selected from 2, 3, 4, and 5. In some embodiments, p is selected from 3, 4, and 5. In some embodiments, p is selected from 4 and 5. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is 6.

[0211] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), R 1 is halogen, OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14), -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R 14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 In some embodiments, R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)N(R 14 ) 2 , -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -S(O)R14 , -S(O) 2 R 14 , -NO 2 , =O, =S, =N(R 14 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, R 1 is halogen, -OR 14 , -N(R 14 ) 2 , -NO 2 , -CN,C 1~6 Alkyl, and C 1~6 In some embodiments, R is selected from haloalkyl. 1 is halogen and -CF 3 In some embodiments, R 1 -CF 3 It is.

[0212] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , -CN, and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -N(R 15 )S(O) 2 R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 In some embodiments, R 2 is halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)N(R 15 ) 2 , -N(R 15 )C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -S(O)R 15 , -S(O) 2 R 15 , -NO 2 , =O, =S, =N(R 15 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, R 2is hydrogen, halogen, -OR 15 , -N(R 15 ) 2 , -C(O)R 15 , -NO 2 , -CN,C 1~3 Alkyl, and C 1~3 In some embodiments, R is selected from haloalkyl. 2 is hydrogen, halogen, and C 1~3 In some embodiments, R 2 is selected from hydrogen, halogen, methyl, and ethyl. 2 is selected from hydrogen and methyl. In some embodiments, R 2 is hydrogen.

[0213] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), each R 3 is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , -CN, and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , and -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16, -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 3 is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O) 2 R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 In some embodiments, each R 3 For each occurrence, halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , and -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 In some embodiments, each R 3 Each occurrence of represents hydrogen and C 1~6 Halogen, -OR 16 , -SR 16 , -N(R 16) 2 , -C(O)R 16 , and -C(O)N(R 16 ) 2 , -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O) 2 R 16 , -NO 2 , =O, =S, =N(R 16 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 3 is hydrogen, halogen, -OR 16 , -N(R 16 ) 2 , -NO 2 , -CN,C 1~3 Alkyl, and C 1~3 In some embodiments, each R 3 Each occurrence of R is independently selected from hydrogen and methyl. 3 is hydrogen.

[0214] In some embodiments, m is 2 for compounds or salts of Formula (III), (IV), (IV-a) and (IV-b).

[0215] In some embodiments, for compounds or salts of Formula (III), (IV), (IV-a) and (IV-b), m is 1.

[0216] In some embodiments, for compounds or salts of Formula (III), (IV), (IV-a) and (IV-b), m is 0.

[0217] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), each R 4 For each occurrence, halogen, -OR 17 , -SR 17, -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , -CN, and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , =O, =S, =N(R 17 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O) 2 R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17, -NO 2 In some embodiments, each R 4 For each occurrence, halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)N(R 17 ) 2 , -N(R 17 )C(O)R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O) 2 R 17 , -NO 2 , =O, =S, =N(R 17 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 4 is halogen, -OR 17 , -N(R 17 ) 2 , -NO 2 , -CN,C 1~3 Alkyl, and C 1~3 In some embodiments, each R 4 is selected from chloro, fluoro, methyl, ethyl, and -CN.

[0218] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), A is optionally substituted C 3~6 In some embodiments, A is an optionally substituted saturated C 3~6 In some embodiments, A is an optionally substituted unsaturated C 3~6 In some embodiments, A is an optionally substituted C 3~5 Carbocyclic, optionally substituted C 3~4 Carbocyclic, optionally substituted C 4~6 Carbocyclic and optionally substituted C 5~6In some embodiments, A is selected from optionally substituted C 3 Carbocyclic, optionally substituted C 4 Carbocyclic, optionally substituted C 5 Carbocyclic and optionally substituted C 6 Carbocycles are selected from the group consisting of:

[0219] In some embodiments, for the compounds or salts of formula (III), (IV), (IV-a) and (IV-b), A is an optionally substituted 5-6 membered heteroaryl. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one heteroatom selected from nitrogen, oxygen and sulfur. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one nitrogen or oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one nitrogen or sulfur heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one sulfur or oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one sulfur heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 membered heteroaryl containing at least one nitrogen heteroatom.

[0220] In some embodiments, for the compounds or salts of formula (III), (IV), (IV-a), and (IV-b), A is a saturated C 3~6 carbocycle and 5-membered heteroaryl, both of which are Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11)S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~6 It is optionally substituted with one or more substituents independently selected from alkyl.

[0221] In some embodiments, for the compounds or salts of formula (III), (IV), (IV-a), and (IV-b), A is a 5-6 membered heteroaryl, each of which is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -N(R 11 )S(O) 2 R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -S(O)R 11 , -S(O) 2 R 11 , -NO 2 , =O, =S, =N(R 11 ), -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -N(R 11 )C(O)R 11, -C(O)OR 11 , -OC(O)R 11 , -NO 2 , =O, =N(R 11 ), and -CN, 1~6 It is optionally substituted with one or more substituents independently selected from alkyl.

[0222] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), A is Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and -CN, 1~6and 5-membered heteroaryl optionally substituted with one or more substituents independently selected from alkyl.

[0223] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), A is halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 In some embodiments, A is a 5-6 membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 , -CN,C 3~6 One or more C rings optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 6-membered heterocycle. 1~6 5-6 membered heteroaryl optionally substituted with alkyl, 3~6 The carbocyclic ring and the 3- to 6-membered heterocyclic ring are each -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and -CN.

[0224] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl and tetrazolyl, any one of which is halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and one or more C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, A is selected from pyrazolyl and oxadiazolyl, each of which is selected from halogen, -OR 11 , -N(R 11 ) 2 , -C(O)OR 11 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with methyl, ethyl, isopropyl, and or propyl. In some embodiments, A is

[0225] [ka] It is.

[0226] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), A is halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6In some embodiments, A is pyrazolyl optionally substituted with alkyl. In some embodiments, A is pyrazolyl optionally substituted with methyl, ethyl, isopropyl, or propyl. In some embodiments, A is

[0227] [ka] It is.

[0228] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), A is selected from pyrazolyl, oxazolyl, isoxazolyl, and oxadiazolyl, any of which is selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)N(R 11 ) 2 , -C(O)OR 11 , -OC(O)R 11 , -NO 2 and one or more C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, A is selected from pyrazolyl, oxazolyl, isoxazolyl, and oxadiazolyl, any of which may be substituted with halogen, -OR 11 , -N(R 11 ) 2 , -C(O)R 11 , -NO 2 and one or more C optionally substituted with one or more substituents independently selected from -CN. 1~6 It is optionally substituted with alkyl.

[0229] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), A is pyrazolyl, oxazolyl, and isoxazolyl, each of which is selected from the group consisting of one or more C 1~6 Alkyl and C 1~6In some embodiments, A is pyrazolyl, oxazolyl, and isoxazolyl, each of which is optionally substituted with one or more of methyl, ethyl, isopropyl, propyl, trifluoromethyl, and trifluoroethyl. In some embodiments, A is

[0230] [ka] In some embodiments, A is selected from:

[0231] [ka] In some embodiments, A is selected from:

[0232] [ka] is selected from.

[0233] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), B is -C(H)(R 5 ) 2 In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -N(R 13 )S(O) 2 R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 3~6 In some embodiments, each R 5 For each occurrence, halogen, -OR 13 , -SR 13 , -N(R 13) 2 , -C(O)R 13 , -C(O)N(R 13 ) 2 , -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -S(O)R 13 , -S(O) 2 R 13 , -NO 2 , =O, =S, =N(R 13 ), and one or more substituents C optionally substituted with one or more substituents independently selected from -CN; 1~6 C optionally substituted with alkyl 3~6 carbocycle.

[0234] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), -C(H)(R 5 ) 2 Each R 5 teeth, Halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; Halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 Alkyl; and Halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, C 1~6 Alkyl, and C 1~6C optionally substituted with one or more substituents independently selected from haloalkyl 3~10 carbocycle.

[0235] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), R 5 is replaced by C 3~10 In some embodiments, R 5 is replaced by C 3~4 Carbocyclic, optionally substituted C 3~5 Carbocyclic, optionally substituted C 3~6 Carbocyclic, optionally substituted C 3~7 Carbocyclic, optionally substituted C 3~8 Carbocyclic and optionally substituted C 3~9 In some embodiments, R 5 is replaced by C 4~10 Carbocyclic, optionally substituted C 5~10 Carbocyclic, optionally substituted C 6~10 Carbocyclic, optionally substituted C 7~10 Carbocyclic, optionally substituted C 8~10 Carbocyclic and optionally substituted C 9~10 In some embodiments, R 5 is replaced by C 3~10 In some embodiments, R 5 is replaced by C 3~10 In some embodiments, R 5 is replaced by C 3~6 Carbocyclic and optionally substituted C 6~10 In some embodiments, R 5 is replaced by C 3~8 Monocyclic carbocycles and optionally substituted C 6~10 bicyclic carbocycles.

[0236] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), -C(H)(R 5 ) 2 Each R5 is halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~6 In some embodiments, -CH(R 5 ) 2 teeth,

[0237] [ka] It is.

[0238] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), -C(H)(R 5 ) 2 Each R 5 is halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), and -CN; and halogen, -OR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , =O, =S, =N(R 13 ), -CN, C 1~6 Alkyl, and C 1~6 C optionally substituted with one or more substituents independently selected from haloalkyl 3~10 C optionally substituted with one or more substituents independently selected from carbocycles 1~6 alkyl.

[0239] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), -C(H)(R 5 ) 2 Each R 5 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~7 cycloalkyl, and phenyl; 3~7 Cycloalkyl and phenyl are each independently halogen, C 1~6 Alkyl, and C 1~6 and optionally substituted with one or more substituents independently selected from haloalkyl. In some embodiments, -C(H)(R 5 ) 2 Each R 5 is C 1~6 Alkyl, C 3~7 cycloalkyl, and phenyl; 3~7 Cycloalkyl and phenyl are each independently halogen and C 1~6 In some embodiments, -C(H)(R 5 ) 2 Each R 5 is C 1~6 Alkyl and C 3~7 In some embodiments, -C(H)(R 5 ) 2 Each R 5 is C 3~7 In some embodiments, -C(H)(R 5 ) 2 Each R 5 is C 1~6 is independently selected from alkyl and phenyl.

[0240] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), -C(H)(R 5 ) 2 teeth,

[0241] [ka] In some embodiments, -C(H)(R 5 ) 2 teeth,

[0242] [ka] In some embodiments, -C(H)(R 5 ) 2 teeth,

[0243] [ka] It is.

[0244] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), B is

[0245] [ka] In some embodiments, B is selected from:

[0246] [ka] In some embodiments, B is

[0247] [ka] It is.

[0248] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), B is optionally substituted C 3~10 In some embodiments, B is an optionally substituted C 3~4 Carbocyclic, optionally substituted C 3~5 Carbocyclic, optionally substituted C 3~6 Carbocyclic, optionally substituted C 3~7 Carbocyclic, optionally substituted C3~8 Carbocyclic and optionally substituted C 3~9 In some embodiments, B is selected from optionally substituted C 4~10 Carbocyclic, optionally substituted C 5~10 Carbocyclic, optionally substituted C 6~10 Carbocyclic, optionally substituted C 7~10 Carbocyclic, optionally substituted C 8~10 Carbocyclic and optionally substituted C 9~10 In some embodiments, B is selected from optionally substituted C 3~10 In some embodiments, B is an optionally substituted C 3~10 In some embodiments, B is an optionally substituted C 3~6 Carbocyclic and optionally substituted C 6~10 In some embodiments, B is selected from optionally substituted C 3~8 Monocyclic carbocycles and optionally substituted C 6~10 bicyclic carbocycles.

[0249] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a), and (IV-b), B is a halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), -CN, and halogens, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 C optionally substituted with one or more substituents independently selected from 6~10 In some embodiments, B is a halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2, =O, =S, =N(R 12 ), -CN, optionally substituted with one or more substituents independently selected from 6~10 In some embodiments, B is a halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and one or more C optionally substituted with one or more substituents independently selected from -CN. 1~6 C optionally substituted with alkyl 6~10 It is a carbocyclic ring.

[0250] In some embodiments, for compounds or salts of formula (III), (IV), (IV-a) and (IV-b), B is selected from cyclohexyl and cycloheptyl, each of which is selected from halogen, -OR 12 , N(R 12 ) 2 -NO 2 , -CN, and halogen, -OR 12 , N(R 12 ) 2 , -C(O)R 12 , -NO 2 , =O, =S, =N(R 12 ), and C optionally substituted with one or more substituents independently selected from -CN. 1~6 In some embodiments, B is selected from cyclohexyl and cycloheptyl, each of which is independently selected from halogen, C 1~6 Alkyl, and C 1ー6 In some embodiments, B is optionally substituted with one or more substituents independently selected from haloalkyl.

[0251] [ka] In some embodiments, B is

[0252] [ka] In some embodiments, B is selected from:

[0253] [ka] In some embodiments, B is

[0254] [ka] It is.

[0255] In some aspects, the present disclosure provides a method for producing a pharmaceutical composition comprising:

[0256] [ka] The present invention provides a compound of formula (III) selected from:

[0257] In some aspects, the present disclosure provides a method for producing a pharmaceutical composition comprising:

[0258] [ka]

[0259] [ka] The present invention provides a compound of formula (III) selected from:

[0260] In certain aspects, the disclosure provides a compound or salt represented by the structure of formula (III): A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 , -CN; and halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 and -CN, optionally substituted with one or more substituents selected from 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 A is optionally substituted with one or more substituents independently selected from carbocycles, e.g., A is 3~10 is a 5-membered heteroaryl optionally substituted with a carbocycle; B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 , -CN; C 1~10 Alkyl and C 3~10 carbocyclic rings, each of which is independently halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 , -CN,C 3~10 is optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle; 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 and -CN, 1~10 Alkyl and C 3~10 Optionally substituted with one or more substituents independently selected from carbocycles, e.g., B is optionally substituted with C 3~10 is a carbocyclic ring, Each R 5 is, for each occurrence, independently selected from the following: (i), (ii), and (iii): (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 )2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN, and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic rings, For example, each R 5 is replaced by C 3~10 Carbocyclic or optionally substituted C 1~10 is alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14, -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 carbocyclic ring, e.g., each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, for example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, e.g., each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 alkyl, e.g., each R 4 is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 11A , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0261] In certain aspects, the disclosure provides a compound or salt represented by the structure of formula (III): A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 and -CN, 1~10 Alkyl; and Halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 , -CN; and halogen, -OR 11A , -SR 11A , -N(R 11A ) 2 , -C(O)R 11A , -C(O)OR 11A , -NO 2 and -CN, optionally substituted with one or more substituents selected from 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 A is optionally substituted with one or more substituents independently selected from carbocycles, e.g., A is 3~10 is a 5-membered heteroaryl optionally substituted with a carbocycle; B is -C(H)(R 5 ) 2 And each R 5 is, for each occurrence, independently selected from the following: (i), (ii), and (iii): (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic rings, For example, each R 5 is replaced by C 3~10 Carbocyclic or optionally substituted C 1~10 alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14 , -SR 14, -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 carbocyclic ring, e.g., each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, for example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, e.g., each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 alkyl, e.g., each R 4 is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 11A , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0262] In certain aspects, the disclosure provides a compound or salt represented by the structure of formula (III), (IV), (IV-a), or (IV-b), wherein: A is a 5-6 membered heteroaryl and C 3~6 carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN; and Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 and -CN, 1~10 A is optionally substituted with one or more substituents independently selected from alkyl, e.g., A is 1~10 is a 5-membered heteroaryl optionally substituted with alkyl; B is -C(H)(R 5 ) 2 and C 3~10 carbocyclic rings, each C 3~10 The carbocycle is Halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 , -CN; C 1~10 Alkyl and C 3~10 carbocyclic rings, each of which is independently halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 , -CN,C 3~10 is optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle; 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 12 , -SR 12 , -N(R 12 ) 2 , -C(O)R 12 , -C(O)OR 12 , -NO 2 and -CN, 1~10 Alkyl and C3~10 Optionally substituted with one or more substituents independently selected from carbocycles, e.g., B is optionally substituted with C 3~10 is a carbocyclic ring, Each R 5 is, for each occurrence, independently selected from the following: (i), (ii), and (iii): (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN, and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic rings, For example, each R 5 is replaced by C 3~10 Carbocyclic or optionally substituted C 1~10 is alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 carbocyclic ring, e.g., each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, for example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, e.g., each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 alkyl, e.g., each R 4is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0263] In certain aspects, the disclosure provides a compound or salt represented by the structure of formula (III), (IV), (IV-a), or (IV-b), wherein: A is a 5-6 membered heteroaryl and C 3~6carbocyclic rings, any of which is selected from Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN; Halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 , -CN,C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~10 Alkyl, C 3~10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, -OR 11 , -SR 11 , -N(R 11 ) 2 , -C(O)R 11 , -C(O)OR 11 , -NO 2 and -CN, for example, A is optionally substituted with one or more substituents selected from C 1~10 is a 5-membered heteroaryl optionally substituted with alkyl; B is -C(H)(R 5 ) 2 And each R 5 is, for each occurrence, independently selected from the following: (i), (ii), and (iii): (i) Halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; (ii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and (iii) halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 , -CN; and halogen, -OR 13 , -SR 13 , -N(R 13 ) 2 , -C(O)R 13 , -C(O)OR 13 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 Carbocyclic rings, For example, each R 5 is replaced by C 3~10 Carbocyclic or optionally substituted C 1~10 alkyl, Each R 1 For each occurrence, Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; Halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 Alkyl; and Halogen, -OR 14 , -SR 14 , -N(R 14 )2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 , -CN; and halogen, -OR 14 , -SR 14 , -N(R 14 ) 2 , -C(O)R 14 , -C(O)OR 14 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 C optionally substituted with one or more substituents independently selected from alkyl 3~10 carbocyclic ring, e.g., each R 1 is C 1~10 is haloalkyl, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 , -CN; and halogen, -OR 15 , -SR 15 , -N(R 15 ) 2 , -C(O)R 15 , -C(O)OR 15 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, for example, R 2 is hydrogen, Each R 3 For each occurrence, Halogen, -OR 16 , -SR 16 , -N(R 16 ) 2 , -C(O)R 16 , -C(O)OR 16 , -NO 2 , -CN; and halogen, -OR 16 , -SR 16 , -N(R 16 ) 2, -C(O)R 16 , -C(O)OR 16 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~6 alkyl, e.g., each R 3 is hydrogen or appropriately substituted C 1~6 is alkyl, Each R 4 For each occurrence, Halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 , -CN; and halogen, -OR 17 , -SR 17 , -N(R 17 ) 2 , -C(O)R 17 , -C(O)OR 17 , -NO 2 and C optionally substituted with one or more substituents independently selected from -CN. 1~10 alkyl, e.g., each R 4 is halogen or appropriately substituted C 1~10 is alkyl, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 For each occurrence, hydrogen; Halogen, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2、 -NO 2 , =O, -CN, C 3~10 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 10-membered heterocycles 1~6 Alkyl, each C 3~10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, -OH, -OC 1~6 Alkyl, -OC1~6 Haloalkyl, -NH 2、 -NO 2 , ═O, and —CN; 1~6 Alkyl; and Halogen, -OH, -OC 1~6 Alkyl, -OC 1~6 Haloalkyl, -NH 2 , -NO 2 , ═O, and —CN, optionally substituted with one or more substituents independently selected from 3~10 is independently selected from a carbocycle and a 3- to 10-membered heterocycle; n is selected from 1 and 2, for example, p is 1; m is selected from 0 and 1, for example, m is 0; p is selected from 0, 1, and 2, for example, p is 1.

[0264] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be used in carrying out the invention. The following claims define the scope of the invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0265] Chemical substances having carbon-carbon or carbon-nitrogen double bonds can exist in Z or E forms (or cis or trans forms). Additionally, some chemical substances can exist in various tautomeric forms. Unless otherwise specified, compounds or salts of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) are intended to include all Z-, E, and tautomeric forms.

[0266] "Isomers" are different compounds that have the same molecular formula. "Stereoisomers" are isomers that differ only in terms of the arrangement of atoms in space. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. The term "(±)" is used to designate a racemic mixture when appropriate. "Diastereoisomers" or "diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is specified according to the Cahn-Ingold-Prelog RS system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified by either R or S. Resolved compounds whose absolute configuration is unknown can be designated (+) or (-) depending on the direction (dextrorotatory or levorotatory) they rotate plane polarized light at the wavelength of the sodium D line. Certain compounds described herein contain one or more asymmetric centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms, which may be defined in terms of absolute stereochemistry as (R)- or (S)-. The chemical compounds, pharmaceutical compositions, and methods of the present invention are meant to include all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers, and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. The optical activity of a compound can be analyzed via any suitable method, including, but not limited to, chiral chromatography and polarimetry, to determine the predominance of one stereoisomer over the other.

[0267] The compounds or salts of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) may exist as diastereomers, enantiomers, or other stereoisomeric forms, as the case may be. The compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms, as well as racemates, diastereomeric mixtures, and other mixtures thereof, to the extent that they can be made by one skilled in the art by routine experimentation. Separation of stereoisomers can be carried out by chromatography, or by forming diastereomers and separating them by recrystallization, or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions", John Wiley And Sons, Inc., 1981, which is incorporated herein by reference for the present disclosure). Stereoisomers can also be obtained by stereoselective synthesis. Furthermore, a mixture of two enantiomers enriched in one of the two enantiomers can be purified to obtain a more optically enriched form of the major enantiomer by recrystallization and / or trituration.

[0268] In certain embodiments, the compound or salt of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) may contain two or more enantiomers or diastereomers of the compound, with a single enantiomer or diastereomer comprising at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 98% by weight, or at least about 99% by weight or more of the total weight of all stereoisomers. Methods for producing substantially pure enantiomers are well known to those skilled in the art. For example, a single stereoisomer, e.g., an enantiomer, substantially free of its stereoisomer, can be obtained by resolution of a racemic mixture using methods such as the formation of diastereomers using optically active resolving agents (Stereochemistry of Carbon Compounds, (1962) by EL Eliel, McGraw Hill; Lochmuller (1975) J. Chromatogr., 113(3):283-302). Racemic mixtures of chiral compounds can be separated and isolated by any suitable method, including, but not limited to, (1) formation of ionic diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing agents, separation of the diastereomers, and conversion to pure stereoisomers, and (3) direct separation under chiral conditions of the substantially pure or enriched stereoisomers. Another approach for separation of enantiomers is to use a Diacel chiral column and elution with an organic mobile phase as performed by Chiral Technologies (www.chiraltech.com) for a fee.

[0269] "Tautomer" refers to a molecule in which a proton transfer from one atom of the molecule to another atom of the same molecule is possible. In certain embodiments, a compound or salt of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) exists as a tautomer. In situations where tautomerization is possible, a chemical equilibrium of tautomers may exist. The exact ratio of tautomers depends on several factors, including physical conditions, temperature, solvent, and pH. Some non-limiting examples of tautomeric equilibrium include the following:

[0270] [ka]

[0271] The compounds of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a) or (IV-b) may be present in different isotopically enriched forms, e.g. 2 H, 3 H, 11 C. 13 C, and / or 14 The compound can be used in a form enriched in C content. In a particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thus extending the duration of action of the drug.

[0272] In certain embodiments, a compound of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) is 1 Some or all of the H atoms 2 It is substituted with an H atom. Methods for the synthesis of deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthesis methods:

[0273] Deuterium substituted compounds are synthesized using a variety of methods such as those described in Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0274] Deuterated starting materials are readily available and can be subjected to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Many deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0275] Unless otherwise stated, compounds of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms, for example, the replacement of hydrogen by deuterium or tritium, or 13 C- or 14 Compounds having the present structure except for the replacement of carbon by a C carbon atom are within the scope of the present disclosure.

[0276] Compounds of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a) or (IV-b) may conveniently contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may contain isotopes such as deuterium ( 2H), tritium ( 3 H), iodine-125( 125 I), or carbon-14 ( 14 C), etc. 2 H, 11 C. 13 C. 14 C. 15 C. 12 N, 13 N, 15 N, 16 N, 16 O. 17 O. 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34S , 35 S, 36 S, 35 Cl, 37 Cl, 79 Br, 81 Br, and 125 All isotopic substitutions at I are contemplated. All isotopic variations of the compounds of the present disclosure, whether radioactive or not, are intended to be included within the scope of the present disclosure.

[0277] The present disclosure includes salts of compounds of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b), particularly pharma- ceutically acceptable salts. Compounds of the present disclosure may have sufficiently acidic functional groups, sufficiently basic functional groups, or both, and may react with any of a number of inorganic bases and inorganic and organic acids to form salts. Alternatively, compounds that are inherently charged (e.g., compounds with a quaternary nitrogen) may form salts with a suitable counterion, such as a halide (e.g., bromide, chloride, or fluoride).

[0278] In certain embodiments, the compound or salt of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) may be a prodrug. The term "prodrug" is intended to encompass compounds that are converted to pharmaceutical agents of the present disclosure under physiological conditions. One way to create a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by the enzyme activity of the host animal, such as a specific target cell in the host animal.

[0279] In some embodiments, the prodrug design increases the lipophilicity of the pharmaceutical agent, hi some embodiments, the prodrug design increases the effective water solubility. See, for example, Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci. 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the ACS Symposium on Drug Delivery, all of which are incorporated herein by reference for their disclosure. Series, and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987.) According to another embodiment, the present disclosure provides a method for producing the compounds defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0280] Synthetic chemistry transformations and methodologies useful for synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. Muts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995).

[0281] Pharmaceutical preparations In some aspects, the disclosure provides a pharmaceutical composition comprising a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) and at least one pharma- ceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) and a pharma- ceutically acceptable excipient.

[0282] The pharmaceutical composition can be formulated using one or more physiologically acceptable carriers, including excipients and auxiliaries. The formulation can be modified according to the selected route of administration. The pharmaceutical composition containing the compound, salt or conjugate can be prepared, for example, by lyophilizing the compound, salt or conjugate, and mixing, dissolving, emulsifying, encapsulating or encapsulating the conjugate. The pharmaceutical composition can also contain the compound, salt or conjugate in free base form or in pharma-ceutically acceptable salt form.

[0283] Pharmaceutical compositions can often further comprise two or more active compounds (e.g., compounds, salts or conjugates and other agents) as required for the particular indication being treated. The active compounds may have complementary activities that do not adversely affect each other. Such molecules can be present in combination in amounts that are effective for the intended purpose.

[0284] The compounds or salts of any one of formulas (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) may be formulated into any suitable pharmaceutical formulation. Pharmaceutical formulations of the present disclosure typically contain an active ingredient (e.g., any one of compounds or salts of formula (I)) and one or more pharma- ceutically acceptable excipients or carriers, including, but not limited to, inert solid diluents and fillers, diluents, sterile aqueous solutions and various organic solvents, permeation enhancers, antioxidants, solubilizers, and adjuvants.

[0285] In certain embodiments, the compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) is formulated with a chelating agent or other material capable of binding metal ions, such as ethylene diamine tetra acetic acid (EDTA), which salt can enhance the stability of the compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b).

[0286] The pharmaceutical formulation may be provided in any suitable form, which may depend on the route of administration.

[0287] In some embodiments, the present disclosure provides a pharmaceutical composition for oral administration, comprising at least one compound or salt of any one of formulas (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b), and a pharmaceutical excipient suitable for oral administration. The composition may be in solid, liquid, gel, semi-liquid, or semi-solid form. In certain embodiments, the composition further comprises a second agent.

[0288] The pharmaceutical compositions of the present disclosure suitable for oral administration can be presented in individual dosage forms, such as hard or soft capsules, cachets, troches, lozenges, or tablets, or as liquids or aerosol sprays, solutions, or suspensions in aqueous or non-aqueous liquids, oil-in-water emulsions or water-in-oil liquid emulsions, or dispersible powders or granules, or as syrups or elixirs, each containing a predetermined amount of active ingredient, whether as a powder or in granules. Such dosage forms can be prepared by any of the methods of pharmacy, which typically include the step of bringing the active ingredient into association with the carrier. In general, the compositions are prepared by uniformly and intimately mixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation. For example, tablets can be prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredients in a free-flowing form such as powder or granules suitably mixed with excipients such as, but not limited to, binders, lubricants, inert diluents, and / or surfactants or dispersing agents. Molded tablets can be made by molding in a suitable machine a mixture of a powdered compound or salt of any one of formulas (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) moistened with an inert liquid diluent.

[0289] Pharmaceutical compositions may also be prepared from a compound or salt of any one of formulas (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) and one or more pharma- ceutically acceptable excipients. Preparation of such pharmaceutical compositions is well known in the art. For example, Anderson, Philip O.; Knoben, James E.; Troutman, William G, eds., Handbook of Clinical Drug Data, Tenth Edition, McGraw-Hill, 2002, Pratt and Taylor, eds., Principles of Drug Action, Third Edition, Churchill Livingston, New York, 1990, Katzung, ed., Basic and Clinical Pharmacology, Ninth Edition, McGraw. See Hill, 2003, Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw Hill, 2001, Remingtons Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins., 2000, Martindale, The Extra Pharmacopoeia, Thirty-Second Edition (The Pharmaceutical Press, London, 1999).

[0290] Treatment method In certain aspects, the disclosure provides a method of modulating IL-17A in a subject in need thereof, comprising administering to the subject a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b), or a pharmaceutical composition thereof.

[0291] Increased levels of IL-17A have been associated with several conditions, including airway inflammation, rheumatoid arthritis (RA), osteoarthritis, bone erosion, intraperitoneal abscesses and adhesions, inflammatory bowel disease (IBD), allograft rejection, psoriasis, psoriatic arthritis, ankylosing spondylitis, certain types of cancer, angiogenesis, atherosclerosis, and multiple sclerosis (MS). Both IL-17A and IL-17R are upregulated in the synovial tissue of RA patients. IL-17A exerts its role in the pathogenesis of RA through IL-1-β and TNF-α-dependent and -independent pathways. IL-17A stimulates the secretion of other cytokines and chemokines, such as TNF-α, IL-1β, IL-6, IL-8, and Gro-α. IL-17A directly contributes to disease progression in RA. Injection of IL-17A into mouse knees promotes joint destruction independent of IL-1β activity (Ann Rheum Dis 2000,59:529-32). Anti-IL-1β antibodies have no effect on IL-17A-induced inflammation and joint damage (J.Immunol 2001,167:1004-1013). In a streptococcal cell wall (SCW)-induced mouse arthritis model, IL-17A induced inflammatory cell infiltration and proteoglycan depletion in wild-type and IL-1β knockout and TNF-α knockout mice. IL-17A knockout mice are phenotypically normal in the absence of antigen challenge but have significantly reduced arthritis after type II collagen immunization (J.Immunol 2003,171:6173-6177). Increased levels of IL-17A secreting cells have also been observed in the facet joints of patients with ankylosing spondylitis (see H Appel et al., Arthritis Res Therap. 2011, 13:R95).

[0292] Multiple sclerosis is an autoimmune disease characterized by central nervous system (CNS) inflammation accompanied by damage to the myelin sheath that surrounds axons. A hallmark of MS is the infiltration of T cells into the CNS. Compared to remission, higher numbers of blood mononuclear cells (MNCs) expressing IL-17A mRNA are detected during MS clinical exacerbations (Multiple Sclerosis, 5:101-104, 1999). Furthermore, experimental autoimmune encephalomyelitis (EAE), a preclinical animal model of MS, is significantly suppressed in IL-17A knockout mice.

[0293] In certain aspects, the disclosure provides a method of modulating IL-17A in a subject in need thereof, comprising administering to the subject a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b), or a pharmaceutical composition thereof. In certain embodiments, the compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) inhibits the activity of IL-17A in a subject in need thereof.

[0294] In certain embodiments, the compounds or salts of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) can be used to treat or prevent diseases or conditions mediated directly or indirectly by IL-17A. Such diseases include inflammatory diseases and conditions, proliferative diseases (e.g., cancer), autoimmune diseases, and other diseases described herein. The methods generally include administering to a subject a therapeutically effective amount of a compound disclosed herein or a pharmaceutical composition thereof. In some embodiments, the inflammatory disease or condition is selected from psoriasis vulgaris, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis.

[0295] In some aspects, the disclosure provides a method of treating or preventing an inflammatory disease or condition in a subject in need thereof, comprising administering to the subject a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b), or a pharmaceutical composition thereof. In certain embodiments, a compound or salt of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) is administered to a subject in need thereof to treat an inflammatory disease or condition, e.g., psoriasis.

[0296] In certain embodiments, the compound or salt of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) is used to treat or prevent an inflammatory disease or condition selected from psoriasis vulgaris, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis. In certain embodiments, the compound or salt of formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) is used to treat or prevent psoriasis. In certain embodiments, the compounds or salts of Formula (I), (II), (II-a), (II-b), (III), (IV), (IV-a), or (IV-b) are used for the treatment or prevention of conditions, including, but not limited to, airway inflammation, ankylosing spondylitis, asthma, RA (including juvenile RA), and other inflammatory disorders, conditions, or diseases. EXAMPLES

[0297] Having generally described the invention, it will be more readily understood by reference to the following examples, which are included solely for the purpose of illustrating certain aspects and embodiments of the invention and are not intended to limit the invention.

[0298] The following synthetic schemes are provided for illustrative purposes, not for limitation. The following examples illustrate various methods for making the compounds described herein. It is understood that those skilled in the art can make these compounds by similar methods or by combining other methods known to those skilled in the art. It is also understood that those skilled in the art can make them in a similar manner to those described below by using appropriate starting materials and modifying the synthetic route as necessary. In general, starting materials and reagents can be obtained from commercial suppliers, or can be synthesized according to sources known to those skilled in the art, or can be prepared as described herein.

[0299] Examples 1-209 provide exemplary procedures for the preparation of the claimed IL-17A modulators. Example 210 provides IL-17 A / A bioassay IC 50 Inhibition data is provided. Abbreviations as used in the examples are as follows: DCM = dichloromethane, MeOH = methanol, ACN = acetonitrile, THF = tetrahydrofuran, EtOAc = ethyl acetate, PE = petroleum ether, DMF = dimethylformamide, DMSO = dimethylsulfoxide, DIEA = diisopropylethylamine, LDA = lithium diisopropylamide, FA = formic acid, TFA = trifluoroacetic acid, iPrOH = isopropyl alcohol, NBS = N-bromosuccinimide.

[0300] Example 1: Preparation of Intermediate 1

[0301] [ka]

[0302] Benzyl (S)-(4-bromo-1,1-dicyclopropyl-3-oxobutan-2-yl)carbamate. (Intermediate 1, Int.1).

[0303] [ka]

[0304] A solution of (S)-2-((tert-butoxycarbonyl)amino)-3,3-dicyclopropylpropanoic acid (15.0 g, 55.6 mmol, 1.00 equiv) and HCl in 1,4-dioxane (4 M, 25.0 mL, 1.80 equiv) in DCM (150 mL) was stirred at 20° C. for 2 h. The reaction mixture was concentrated under reduced pressure to give (S)-2-amino-3,3-dicyclopropylpropanoic acid (11.0 g, 53.4 mmol, 96% yield, HCl salt) as a white solid. LCMS [M+H] + =170.1 m / z.

[0305] [ka]

[0306] To a solution of (S)-2-amino-3,3-dicyclopropylpropanoic acid (11.0 g, 53.4 mmol, 1.00 equiv., HCl salt) in THF (100 mL) and water (50.0 mL) was added benzyl (2,5-dioxopyrrolidin-1-yl)carbonate (26.7 g, 106 mmol, 2.00 equiv.) and NaCO 3 (13.5 g, 160 mmol, 6.24 mL, 3.00 equiv.) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with 1 M aqueous HCl to pH=4, extracted with EtOAc and washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave a residue which was purified by column chromatography (SiO 2 , PE / EtOAc) to give (S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanoic acid (10.0 g, 32.9 mmol, 62% yield) as a white solid. 1 H NMR (400 MHz, CDCl 3 )d 7.41-7.30(m,5H),5.57(d,J=9.2Hz,1H),5.14(s,2H),4.73-4.47(m,1H),0.88-0.67(m,3H),0.59-0.35(m,4H),0.32-0.13(m,4H). LCMS[M+H] + =304.2m / z.

[0307] [ka]

[0308] A solution of (S)-2-(((benzyloxy)carbonyl)amino)-3,3-dicyclopropylpropanoic acid (20.0 g, 65.9 mmol, 1.00 equiv) and 1,1'-carbonyldiimidazole (11.8 g, 72.5 mmol, 1.10 equiv) in THF (250 mL) was stirred at 0° C. for 2 h. Meanwhile, to a solution of tert-butyl acetate (23.0 g, 198 mmol, 26.5 mL, 3.00 equiv) in THF (250 mL) was added a solution of LDA (2 M, 98.9 mL, 3.00 equiv) and the reaction mixture was stirred at −78° C. for 2 h. The two reaction mixtures were combined and stirred at −78° C. for 2 h. The reaction mixture was diluted with NH 4 Dilute with a saturated aqueous solution of Cl, extract with EtOAc, and 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave a residue which was purified by column chromatography (SiO 2 , PE / EtOAc) to give tert-butyl (S)-4-(((benzyloxy)carbonyl)amino)-5,5-dicyclopropyl-3-oxopentanoate (15.0 g, 37.3 mmol, 57% yield) as a yellow oil. LCMS [M+Na] + =424.3m / z.

[0309] [ka]

[0310] To a solution of tert-butyl (S)-4-(((benzyloxy)carbonyl)amino)-5,5-dicyclopropyl-3-oxopentanoate (15.0 g, 37.3 mmol, 1.00 equiv) in MeOH (150 mL) was added NBS (5.32 g, 29.8 mmol, 0.800 equiv) and 2,6-dimethylpyridine (321 mg, 2.99 mmol, 348 mL, 0.0800 equiv) at 0° C. The reaction mixture was stirred at 15° C. for 2 h. The reaction mixture was concentrated under reduced pressure to give tert-butyl (4S)-4-(((benzyloxy)carbonyl)amino)-2-bromo-5,5-dicyclopropyl-3-oxopentanoate (15.0 g, 31.2 mmol, 84% yield) as a yellow solid. LCMS [M+H] + =480.2m / z.

[0311] [ka]

[0312] To a solution of tert-butyl (4S)-4-(((benzyloxy)carbonyl)amino)-2-bromo-5,5-dicyclopropyl-3-oxopentanoate (15.0 g, 31.2 mmol, 1.00 equiv.) in toluene (150 mL) was added TFA (17.8 g, 156 mmol, 11.5 mL, 5.00 equiv.). The reaction mixture was stirred at 80° C. for 2 h. The residue was dissolved in NaCO 3 Dilute to pH=7 with a saturated aqueous solution of ethyl acetate, extract with EtOAc, and 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered, and concentrated under reduced pressure to give a residue, which was purified by prep-HPLC (neutral conditions; column: Kromasil Eternity XT (250 mm × 80 mm, 10 mm); mobile phase: [water (NH 4 HCO 3)-ACN]; B%: 45%-75%, to give benzyl (S)-(4-bromo-1,1-dicyclopropyl-3-oxobutan-2-yl)carbamate. The title compound was isolated as the first eluting single stereoisomer (6.00 g, 15.7 mmol, 50% yield) by chiral SFC purification (column: Daicel Chiralcel OJ (250 mm x 50 mm, 10 mm); mobile phase: [Neu-MeOH]; B%: 20%-20%, 4.3 min); and obtained as a white solid. 1 H NMR (400 MHz, CDCl 3 )d 7.43-7.31(m,5H),5.65-5.55(d,J=8.0Hz,1H),5.12(s,2H),4.88-4.78(m,1H ),4.26-4.10(m,2H),0.79-0.63(m,3H),0.59-0.41(m,4H),0.30-0.14(m,4H). LCMS[M+H] + =380.1 m / z.

[0313] Example 2: Preparation of intermediate 2

[0314] [ka]

[0315] Benzyl (S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate. (Intermediate 2, Int.2).

[0316] [ka] A solution of (S)-2-(((benzyloxy)carbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (30.0 g, 91.6 mmol, 1.00 equiv) and 1,1'-carbonyldiimidazole (16.3 g, 100 mmol, 1.10 equiv) in THF (320 mL) was stirred at 0° C. for 2 h. Meanwhile, to a solution of tert-butyl acetate (31.9 g, 274 mmol, 36.8 mL, 3.00 equiv) in THF (200 mL) was added a solution of LDA (2 M, 160 mL, 3.50 equiv) and the mixture was stirred at −70° C. for 1 h. The two reaction mixtures were mixed and stirred at −70° C. for 1 h. The reaction mixture was diluted with NH 4 Dilute with a saturated aqueous solution of Cl, extract with EtOAc, wash with brine, and 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave a residue which was purified by column chromatography (SiO 2 , PE / EtOAc) to give tert-butyl (S)-4-(((benzyloxy)carbonyl)amino)-4-(4,4-difluorocyclohexyl)-3-oxobutanoate (30.0 g, 70.5 mmol, 77% yield) as a yellow oil. LCMS [M+Na] + =448.1m / z.

[0317] [ka]

[0318] To a solution of tert-butyl (S)-4-(((benzyloxy)carbonyl)amino)-4-(4,4-difluorocyclohexyl)-3-oxobutanoate (30.0 g, 70.5 mmol, 1.00 equiv) in MeOH (300 mL) was added NBS (10.0 g, 56.4 mmol, 0.800 equiv) and 2,6-dimethylpyridine (610 mg, 5.64 mmol, 0.08 equiv) at 0° C. The mixture was stirred at room temperature for 2 h. The reaction was cooled to room temperature with NaCO 3 Dilute with a saturated aqueous solution of ethyl acetate, extract with EtOAc, and 2 SO 4Drying at 40° C., filtration and concentration under reduced pressure gave tert-butyl (4S)-4-(((benzyloxy)carbonyl)amino)-2-bromo-4-(4,4-difluorocyclohexyl)-3-oxobutanoate (20.0 g, 39.6 mmol, 56% yield) as a yellow solid which was used in the next step without further purification.

[0319] [ka]

[0320] To a solution of tert-butyl (4S)-4-(((benzyloxy)carbonyl)amino)-2-bromo-4-(4,4-difluorocyclohexyl)-3-oxobutanoate (20.0 g, 39.6 mmol, 1.00 equiv.) in toluene (300 mL) was added TFA (27.1 g, 237 mmol, 17.6 mL, 6.00 equiv.). The reaction mixture was stirred at 75° C. for 2 h. The reaction mixture was diluted with NaCO 3 Dilute with a saturated aqueous solution of ethyl acetate, extract with EtOAc, and 2 SO 4 The mixture was dried at 40° C. for 24 hours, filtered, and concentrated under reduced pressure to give a residue which was purified by prep-HPLC (basic conditions; column: Kromasil Eternity XT (250 mm×80 mm, 10 mm); mobile phase: [water (NH 4 HCO 3 )-ACN]; B%: 45%-70%, 20 min) to give benzyl (S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate. The title compound was isolated as the first eluting single stereoisomer (12.0 g, 26.4 mmol, 67% yield) by chiral SFC purification (column: Daicel Chiralcel OJ (250 mm x 50 mm, 10 mm); mobile phase: [Neu-MeOH]; B%: 20%-20%, 4.3 min); and obtained as a white solid. 1 H NMR (400 MHz, CDCl 3)d 7.04-7.34(m,5H),5.34(d,J=8.8Hz,1H),5.12(s,2H),4.67(dd,J=5.2Hz,J=8.8Hz, 1H),4.03(d,J=7.2Hz,2H),2.15-2.12(m,2H),1.97-1.94(m,1H),1.81-1.35(m,6H). LCMS[M+H] + =404.0 m / z.

[0321] Example 3: Preparation of intermediate 3

[0322] [ka]

[0323] Benzyl (S)-(3-bromo-1-cycloheptyl-2-oxopropyl)carbamate. (Intermediate 3, Int.3).

[0324] [ka]

[0325] To a solution of (S)-2-((tert-butoxycarbonyl)amino)-2-cycloheptylacetic acid (45.0 g, 147 mmol, 1.00 equiv) in DCM (400 mL) was added HCl in 1,4-dioxane (4.00 M, 368 mL, 10.0 equiv) at 0° C. The mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated under reduced pressure to give (S)-2-amino-2-cycloheptylacetic acid (30.0 g, 144 mmol, 98% yield, HCl salt) as a white solid. LCMS [M+H] + =172.2m / z.

[0326] [ka]

[0327] To a solution of (S)-2-amino-2-cycloheptylacetic acid (30.0 g, 144 mmol, 1.00 equiv., HCl salt) in THF (300 mL) and water (100 mL) was added benzyl (2,5-dioxopyrrolidin-1-yl)carbonate (71.9 g, 288 mmol, 2.00 equiv.) and NaCO 3 (36.4 g, 433 mmol, 16.8 mL, 3.00 equiv.) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with 1 M aqueous HCl to adjust pH=2, and then extracted with DCM. The combined organic layers were washed with anhydrous Na 2 SO 4 The mixture was dried over 1000 ml of water, filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO 2 , PE / EtOAc) to give (S)-2-(((benzyloxy)carbonyl)amino)-2-cycloheptylacetic acid (43.0 g, 140 mmol, 97% yield) as a white solid. 1 H NMR (400 MHz, CDCl 3 )d 7.42-7.31(m,5H),5.27(d,J=9.2Hz,1H),5.13(s,2H),4.40-4.37(dd,J1=4.0,J2=8.8Hz,1H),2.19-2.05(d,J=3.5Hz,1H),1.80-1.30(m,12H). LCMS[M+H] + =306.1 m / z.

[0328] [ka]

[0329] A solution of (S)-2-(((benzyloxy)carbonyl)amino)-2-cycloheptylacetic acid (56.0 g, 183 mmol, 1.00 equiv) and 1,1'-carbonyldiimidazole (32.7 g, 201 mmol, 1.10 equiv) in THF (600 mL) was stirred at 0° C. for 2 h. Meanwhile, to a solution of tert-butyl acetate (63.9 g, 550 mmol, 73.7 mL, 3.00 equiv) in THF (500 mL) was added a solution of LDA (2 M, 275 mL, 3.00 equiv) and the reaction mixture was stirred at −78° C. for 2 h. The two reaction mixtures were combined and stirred at −78° C. for 2 h. The reaction mixture was diluted with NH 4 Treat with a saturated aqueous solution of Cl, extract with EtOAc, and 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave a residue which was purified by column chromatography (SiO 2 , PE / EtOAc) to give tert-butyl (S)-4-(((benzyloxy)carbonyl)amino)-4-cycloheptyl-3-oxobutanoate (36.0 g, 89.2 mmol, 49% yield) as a white solid. 1 H NMR (400 MHz, CDCl 3 )d 7.39-7.31(m,5H),5.37(d,J=8.8Hz,1H),5.12(s,2H),4.50-4.47(dd,J1=3.6,J2=8.8Hz,1H),3 .48-3.42(m,2H),2.14-2.06(m,1H),1.85-1.55(m,7H),1.49-1.44(m,11H),1.39-1.13(m,3H). LCMS[M+Na] + =426.2m / z.

[0330] [ka]

[0331] To a solution of tert-butyl (S)-4-(((benzyloxy)carbonyl)amino)-4-cycloheptyl-3-oxobutanoate (36.0 g, 89.2 mmol, 1.00 equiv) in MeOH (400 mL) was added NBS (13.5 g, 75.8 mmol, 0.85 equiv) and 2,6-dimethylpyridine (771 mg, 7.14 mmol, 0.08 equiv) at 0° C. The reaction mixture was stirred at 15° C. for 2 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with NaCO 3 Wash with a saturated aqueous solution of anhydrous Na 2 SO 4 Drying at 40° C., filtration and concentration under reduced pressure gave tert-butyl (4S)-4-(((benzyloxy)carbonyl)amino)-2-bromo-4-cycloheptyl-3-oxobutanoate (40.0 g, 82.9 mmol, 93% yield) as a yellow oil which was used directly in the next step without further purification.

[0332] [ka]

[0333] To a solution of tert-butyl (4S)-4-(((benzyloxy)carbonyl)amino)-2-bromo-4-cycloheptyl-3-oxobutanoate (40.0 g, 82.9 mmol, 1.00 equiv) in toluene (400 mL) was added TFA (56.7 g, 497 mmol, 36.8 mL, 6.00 equiv) at 0° C. The reaction mixture was stirred at 75° C. for 2 h. The reaction mixture was diluted with water and diluted with NaCO 3 A saturated aqueous solution of was added to adjust the pH to 9. The reaction mixture was extracted with DCM and the combined organic layers were washed with anhydrous Na 2 SO 4 The mixture was dried at 40° C. for 24 hours, filtered, and concentrated under reduced pressure to give a residue which was purified by prep-HPLC (basic conditions; column: Kromasil Eternity XT (250 mm×80 mm, 10 mm); mobile phase: [water (NH 4OH)-ACN]; B%: 55%-85%, 20 min), to give benzyl (S)-(3-bromo-1-cycloheptyl-2-oxopropyl)carbamate. The title compound was purified by chiral SFC (column: Daicel Chiralcel OJ (250 mm × 30 mm, 10 mm); mobile phase: [0.1% NH in IPA]. 3 H 2 O]; B%: 20% to 20%, 3 min); was isolated as the first eluting single stereoisomer (11.3 g, 29.5 mmol, 36% yield) as a white solid. 1 H NMR(400MHz,MeOD)d 7.39-7.27(m,5H),5.10(s,2H),4.45-4.37(m,1H),4.22(s,2H),2.21-2.04(m,1H),1.70-1.28(m,12H). LCMS[M+H] + =384.2m / z.

[0334] Example 4: Preparation of Compound 1

[0335] [ka]

[0336] N-((1S)-(4,4-difluorocyclohexyl)(6-((2-oxopyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compound 1).

[0337] [ka]

[0338] To a solution of 6-((tert-butoxycarbonyl)amino)pyridazine-3-carboxylic acid (2.00 g, 8.36 mmol, 1.00 equiv.) in THF (80.0 mL) was added 1,1'-carbonyldiimidazole (4.28 g, 25.1 mmol, 3.00 equiv.). The resulting mixture was stirred at room temperature for 2 h and then dissolved in NaBH in water (10 mL). 4(791 mg, 20.9 mmol, 2.50 equiv.) was added. The reaction mixture was further stirred at room temperature for 2 h. After removal of the solvent, the residue was treated with water and extracted with EtOAc. The combined organics were washed with brine and washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave a residue which was purified by column chromatography (SiO 2 , PE / EtOAc) to give tert-butyl (6-(hydroxymethyl)pyridazin-3-yl)carbamate (1.15 g, 5.1 mmol, 61% yield) as a colorless oil.

[0339] [ka]

[0340] To a solution of tert-butyl (6-(hydroxymethyl)pyridazin-3-yl)carbamate (0.6 g, 2.66 mmol, 1.00 equiv) in DCM (30 mL) was added Dess-Martin periodinane (1.22 g, 2.80 mmol, 1.05 equiv). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was washed with a 1 M aqueous solution of NaOH and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and diluted with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave tert-butyl (6-formylpyridazin-3-yl)carbamate (0.4 g, 1.78 mmol, 67% yield) as a brown solid. 1 H NMR (400 MHz, CDCl 3 )d 10.24(s,1H),8.39(d,J=9.28Hz,1H),8.01(d,J=9.38Hz,1H),1.56(s,9H).

[0341] [ka]

[0342] To a solution of tert-butyl (6-formylpyridazin-3-yl)carbamate (1.25 g, 9.86 mmol, 1.00 equiv) in THF (44.0 mL) was added NaH (788 mg, 19.7 mmol, 2.00 equiv) at 0° C., followed by 1-acetylpyrrolidin-2-one (1.10 g, 4.93 mmol, 0.5 equiv). The reaction mixture was allowed to warm to room temperature and stirred for 16 h. The reaction mixture was quenched with ice water and extracted with EtOAc. The combined organic layers were washed with brine and diluted with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave a residue which was purified by column chromatography (SiO 2 , DCM / MeOH), to give tert-butyl (E)-(6-((2-oxopyrrolidin-3-ylidene)methyl)pyridazin-3-yl)carbamate (540 mg, 3.75 mmol, 38% yield) as a colorless oil. LCMS [M+H] + =291.1m / z.

[0343] [ka]

[0344] To a solution of tert-butyl (E)-(6-((2-oxopyrrolidin-3-ylidene)methyl)pyridazin-3-yl)carbamate (20 mg, 0.069 mmol, 1.00 equiv.) in MeOH (10 mL) was added Pd / C (36.7 mg, 10% purity) and the reaction mixture was first purged with argon, then evacuated and cooled with H 2 The reaction mixture was purged with H 2 The reaction mixture was stirred under pressure for 16 h. The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO 2 , DCM / MeOH) to give tert-butyl (6-((2-oxopyrrolidin-3-yl)methyl)pyridazin-3-yl)carbamate (14 mg, 0.048 mmol, 70% yield) as a yellow solid. 1 H NMR (400 MHz, CDCl 3)d 8.12(d,J=9.18Hz,1H),7.69(s,1H),7.38(d,J=9.20Hz,1H),5.90(s,1H),3.40(dd,J=14.27,4.22Hz,1H),3.20-3.31(m,2H),3 .01(dd,J=14.27,8.91Hz,1H),2.90(qd,J=8.93,4.20Hz,1H),2.23-2.31(m,1H),1.94(dq,J=12.92,8.84Hz,1H),1.51(s,9H). LCMS[M+H] + =293.2m / z.

[0345] [ka]

[0346] To a solution of tert-butyl (6-((2-oxopyrrolidin-3-yl)methyl)pyridazin-3-yl)carbamate (60 mg, 0.205 mmol, 1.00 equiv) in DCM (1.5 mL) was added TFA (1.5 mL). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then concentrated under reduced pressure to give 3-((6-aminopyridazin-3-yl)methyl)pyrrolidin-2-one (60 mg, 0.196 mmol, 95% yield, TFA salt) as a pale pink solid. LCMS [M+H] + =193.1m / z.

[0347] [ka]

[0348] To a solution of 3-((6-aminopyridazin-3-yl)methyl)pyrrolidin-2-one (60 mg, 0.196 mmol, 1.47 equiv, TFA salt) and benzyl (S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate (Int.2; 50 mg, 0.124 mmol, 1.00 equiv) in THF (2.5 mL) was added trimethylborate (57 mg, 0.534 mmol, 0.06 mL, 4.00 equiv) and DIEA (86 mg, 0.667 mmol, 0.116 mL, 5.00 equiv). The reaction mixture was stirred at 75° C. for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO 2 , DCM / MeOH), benzyl ((1S)-(4,4-difluorocyclohexyl)(6-((2-oxopyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)carbamate (40 mg, 0.08 mmol, 65% yield) was obtained as a yellow oil. LCMS [M+H] + =498.2m / z.

[0349] [ka]

[0350] To a solution of benzyl ((1S)-(4,4-difluorocyclohexyl)(6-((2-oxopyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)carbamate (40 mg, 0.08 mmol, 1.00 equiv.) in MeOH (20 mL) was added Pd / C (43 mg, 10% purity) and the reaction mixture was first purged with argon, then evacuated and purged with H. 2 The reaction mixture was purged with H 2 The mixture was stirred under reduced pressure for 30 h. The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to give 3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)pyrrolidin-2-one (29 mg, 0.08 mmol, 99% yield) as a yellow solid. LCMS [M+H] +=364.2m / z.

[0351] [ka]

[0352] To a solution of 3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)pyrrolidin-2-one (29 mg, 0.08 mmol, 1.00 equiv.) and 1-ethyl-1H-pyrazole-5-carboxylic acid (22.4 mg, 0.160 mmol, 2.00 equiv.) in pyridine (2.5 mL) was added EDCI (61.2 mg, 0.319 mmol, 4.00 equiv.) and 4-dimethylaminopyridine (4.9 mg, 0.040 mmol, 0.50 equiv.). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in water and extracted with EtOAc. The combined organic layers were washed with brine and Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave a residue which was purified by column chromatography (SiO 2 , DCM / MeOH) to give N-((1S)-(4,4-difluorocyclohexyl)(6-((2-oxopyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. The title compound was purified using chiral SFC (column: Daicel Chiralpak AS (250 mm×30 mm, 10 mm); mobile phase: [0.1% NH in MeOH]. 3 H 2 0]; B%: 40% to 40%, 3 min); isolated as the first eluting single stereoisomer (2.71 mg, 5.58 mmol, 37% yield, 89% purity) as a white solid. LCMS [M+H] + =486.3m / z.

[0353] Example 5: Preparation of Compound 2

[0354] [ka]

[0355] N-((1S)-cycloheptyl(6-((2-oxopiperidin-3-yl)methyl)imidazole[1,2-b]pyridazin-2-yl)methyl)-4-methyl-1,2,5-oxadiazole-3-carboxamide. (Compound 2).

[0356] [ka]

[0357] To a solution of tert-butyl (6-(chloromethyl)pyridazin-3-yl)carbamate (1.27 g, 4.92 mmol, 1.20 equiv) in THF (20.0 mL) was added Cs 2 CO 3 (2.67 g, 8.21 mmol, 2.00 equiv.) was added. The resulting reaction mixture was stirred at 20° C. for 1 h, and then 1-(tert-butyl) 3-methyl 2-oxopiperidine-1,3-dicarboxylate (1.00 g, 4.10 mmol, 1.00 equiv.) was added. The reaction mixture was stirred at 70° C. for 2 h. The reaction mixture was diluted with water, extracted with EtOAc, and washed with anhydrous Na 2 SO 4 Drying at 40° C., filtration, and concentration under reduced pressure gave a residue which was purified by recrystallization from EtOAc at 20° C. to give 1-(tert-butyl) 3-methyl 3-((6-((tert-butoxycarbonyl)amino)pyridazin-3-yl)methyl)-2-oxopiperidine-1,3-dicarboxylate (1.10 g, 2.37 mmol, 58% yield) as a pale yellow solid. 1 H NMR (400 MHz, CDCl 3 )d 8.09(d,J=9.2Hz,1H),7.65(s,1H),7.45(d,J=9.2Hz,1H),3.75(s,3H),3.64-3.59(m,2 H),3.50-3.45(m,2H),2.25-2.08(m,2H),1.90-1.76(m,2H),1.52(s,9H),1.49(s,9H). LCMS[M+H] + =465.4m / z.

[0358] [ka]

[0359] To a solution of 1-(tert-butyl) 3-methyl 3-((6-((tert-butoxycarbonyl)amino)pyridazin-3-yl)methyl)-2-oxopiperidine-1,3-dicarboxylate (1.00 g, 2.15 mmol, 1.00 equiv) in DCM (5.00 mL) was added TFA (15.4 g, 135 mmol, 10.0 mL, 62.7 equiv) at 0° C. and the reaction mixture was stirred at 20° C. for 2 h. The reaction mixture was filtered and concentrated under reduced pressure to give methyl 3-((6-aminopyridazin-3-yl)methyl)-2-oxopiperidine-3-carboxylate (1.10 g, crude, TFA salt) as a yellow oil. LCMS [M+H] + =265.1 m / z.

[0360] [ka]

[0361] To a solution of methyl 3-((6-aminopyridazin-3-yl)methyl)-2-oxopiperidine-3-carboxylate (700 mg, 1.85 mmol, 1.00 equiv., TFA salt) and benzyl (S)-(3-bromo-1-cycloheptyl-2-oxopropyl)carbamate (Int.3; 707 mg, 1.85 mmol, 1.00 equiv.) in THF (10.0 mL) was added trimethylborate (961 mg, 9.25 mmol, 1.04 mL, 5.00 equiv.) and DIEA (2.39 g, 18.5 mmol, 3.22 mL, 10.0 equiv.). The reaction mixture was stirred at 70° C. for 3 h. The reaction mixture was diluted with water, extracted with EtOAc and washed with anhydrous Na 2 SO 4Drying at 40° C., filtering and concentrating under reduced pressure gave a residue, which was purified by prep-HPLC (column: Phenomenex luna C18 150*40mm*15mm; mobile phase: [water (FA)-ACN]; B%: 42%-72%, 10 min) to give methyl 3-((2-((S)-(((benzyloxy)carbonyl)amino)(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (350 mg, 639 mmol, 35% yield) as a yellow solid. LCMS [M+H] + =548.5m / z.

[0362] [ka]

[0363] To a solution of methyl 3-((2-((S)-(((benzyloxy)carbonyl)amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (350 mg, 639 mmol, 1.00 equiv.) in THF (5.00 mL) was added Pd / C (100 mg, 10.0% purity). The reaction mixture was cooled to 5° C. for 1 h. 2 The mixture was stirred under (25 psi) at 20° C. for 3 h. The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to give methyl 3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (200 mg, 484 mmol, 76% yield) as a pale yellow solid. LCMS [M+H] + =414.2m / z.

[0364] [ka]

[0365] To a solution of methyl 3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (100 mg, 242 mmol, 1.00 equiv.) and 4-methyl-1,2,5-oxadiazole-3-carboxylic acid (46.5 mg, 363 mmol, 1.50 equiv.) in pyridine (3.00 mL) was added EDCI (139 mg, 725 mmol, 3.00 equiv.). The reaction mixture was stirred at 20° C. for 2 h. The reaction mixture was diluted with water, extracted with EtOAc and washed with anhydrous Na 2 SO 4 Drying at 40° C., filtration and concentration under reduced pressure gave a residue which was purified by prep-TLC (SiO 2 , DCM / MeOH) to give methyl 3-((2-((S)-cycloheptyl(4-methyl-1,2,5-oxadiazole-3-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (70.0 mg, 134 mmol, 55% yield) as a white solid. LCMS [M+H] + =524.2m / z.

[0366] [ka]

[0367] To a solution of methyl 3-((2-(S)-cycloheptyl(4-methyl-1,2,5-oxadiazole-3-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (70.0 mg, 134 mmol, 1.00 equiv) in THF (3.00 mL) and water (3.00 mL), LiOH·H 2 2H2O (16.8 mg, 401 mmol, 3.00 equiv.) was added. The reaction mixture was stirred at 20° C. for 3 h. The pH of the reaction mixture was adjusted to 5 with 1 M HCl, extracted with EtOAc, and washed with anhydrous Na 2 SO 4Drying at 40° C., filtering, and concentrating under reduced pressure afforded 3-((2-((S)-cycloheptyl(4-methyl-1,2,5-oxadiazole-3-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylic acid (55.0 mg, 108 mmol, 81% yield) as a white solid.

[0368] [ka]

[0369] To a solution of 3-((2-((S)-cycloheptyl(4-methyl-1,2,5-oxadiazole-3-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylic acid (55.0 mg, 108 mmol, 1.00 equiv.) in DMSO (2.00 mL) was added NaCl (12.6 mg, 216 mmol, 2.00 equiv.). The reaction mixture was stirred at 120° C. for 2 h. The reaction mixture was then diluted with EtOAc, washed with water, and the combined organic layers were extracted with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO 2 , DCM / MeOH), to give N-((1S)-cycloheptyl(6-((2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-4-methyl-1,2,5-oxadiazole-3-carboxamide (3.18 mg, 5.70 mmol, 5% yield, 84% purity) as a white solid. LCMS [M+H] + =466.2m / z.

[0370] Example 6: Preparation of Compound 3

[0371] [ka]

[0372] N-((1S)-cycloheptyl(6-((2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compound 3).

[0373] [ka]

[0374] To a solution of 1-(tert-butyl) 3-methyl 2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate (350 mg, 1.08 mmol, 1.00 equiv) in THF (4.00 mL) was added Cs 2 CO 3 (1.40 g, 4.30 mmol, 4.00 equiv.) was added. The reaction mixture was stirred at 15° C. for 30 min, then tert-butyl (6-(chloromethyl)pyridazin-3-yl)carbamate (262 mg, 1.08 mmol, 1.00 equiv.) was added. The reaction mixture was stirred at 55° C. for 12 h. The reaction mixture was diluted with water, extracted with EtOAc, and washed with anhydrous Na 2 SO 4 The mixture was dried over 1000 ml, filtered, and concentrated under reduced pressure. The resulting residue was purified by prep-HPLC (column: Waters Xbridge C18 150*50mm*10mm; mobile phase: [water (NH4HCO3)-ACN]; B%: 45%~75%, 10 min) to give 1-(tert-butyl) 3-methyl 3-((6-((tert-butoxycarbonyl)amino)pyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate (80.0 mg, 150 mmol, 14% yield) as a yellow oily solid. LCMS [M+H] + =533.3m / z.

[0375] [ka]

[0376] To a solution of 1-(tert-butyl) 3-methyl 3-((6-((tert-butoxycarbonyl)amino)pyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate (40.0 mg, 75.1 mmol, 1.00 equiv) in DCM (0.50 mL) was added TFA (1.54 g, 13.5 mmol, 1.00 mL, 179 equiv) at 0° C. The reaction mixture was stirred at 20° C. for 2 h. The reaction mixture was concentrated under reduced pressure to give methyl 3-((6-aminopyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (30 mg, crude, TFA salt) as a yellow solid.

[0377] [ka]

[0378] To a solution of methyl 3-((6-aminopyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (40.0 mg, 89.6 mmol, 1.00 equiv, TFA salt) and benzyl (S)-(3-bromo-1-cycloheptyl-2-oxopropyl)carbamate (Int.3; 55.2 mg, 144 mmol, 1.61 equiv) in THF (2.00 mL) was added trimethylborate (46.5 mg, 448 mmol, 50.6 mL, 5.00 equiv) and DIEA (115 mg, 896 mmol, 156 mL, 10.0 equiv). The reaction mixture was stirred at 70° C. for 2 h. The reaction mixture was diluted with water, extracted with EtOAc and washed with anhydrous Na 2 SO 4 Drying at 40° C., filtration and concentration under reduced pressure gave a residue which was purified by prep-TLC (SiO 2 , PE / EtOAc) to give methyl 3-((2-((S)-(((benzyloxy)carbonyl)amino)(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (60.0 mg, crude) as a yellow solid. LCMS [M+H] +=616.2m / z.

[0379] [ka]

[0380] To a solution of methyl 3-((2-((S)-(((benzyloxy)carbonyl)amino)(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (60.0 mg, 97.4 mmol, 1.00 equiv.) in THF (3.00 mL) was added Pd / C (40.0 mg, 10% purity). The reaction mixture was cooled to 5° C. for 1 hour and then cooled to 5° C. 2 The mixture was stirred under (15 psi) at 18° C. for 5 h. The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to give methyl 3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (50.0 mg, crude) as a yellow solid. LCMS [M+H] + =482.3m / z.

[0381] [ka]

[0382] To a solution of methyl 3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (40.0 mg, 83.0 mmol, 1.00 equiv.) and 1-ethyl-1H-pyrazole-5-carboxylic acid (13.9 mg, 99.6 mmol, 1.20 equiv.) in pyridine (1.00 mL) was added EDCI (63.7 mg, 332 mmol, 4.00 equiv.). The reaction mixture was stirred at 18° C. for 2 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layer was washed with anhydrous Na 2 SO 4The resulting residue was purified by prep-TLC (SiO 2 , EtOAc / MeOH) to give methyl 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (45.0 mg, 74.5 mmol, 90% yield) as a yellow solid. LCMS [M+H] + =604.4m / z.

[0383] [ka]

[0384] To a solution of methyl 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (45.0 mg, 74.5 mmol, 1.00 equiv) in THF (2.00 mL) and water (0.50 mL), LiOH·H 2 0 (9.38 mg, 223 mmol, 3.00 equiv.) was added. The reaction mixture was stirred at 18° C. for 6 h. The reaction mixture was adjusted to pH=4 with 1 M aqueous HCl. The reaction mixture was concentrated under reduced pressure to give 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylic acid (40.0 mg, 67.8 mmol, 91% yield) as a white solid. LCMS [M+H] + =590.4m / z.

[0385] [ka]

[0386] To a solution of 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylic acid (40.0 mg, 67.8 mmol, 1.00 equiv.) in DMSO (1.00 mL) was added NaCl (11.8 mg, 203 mmol, 3.00 equiv.). The reaction mixture was stirred at 120° C. for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue, which was purified by prep-HPLC (neutral condition; column: Phenomenex Luna C18 (150 mm x 25 mm, 10 mm); mobile phase: [water (HCOOH)-ACN]; B%: 41% to 71%, 10 min) to give N-((1S)-cycloheptyl(6-((2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (20.14 mg, 35.4 mmol, 52% yield) as a white solid. LCMS [M+H] + =546.3m / z.

[0387] Example 7: Preparation of Compound 4

[0388] [ka]

[0389] N-((1S)-cycloheptyl(6-((2-oxopyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compound 4).

[0390] [ka]

[0391] To a solution of 1-ethyl-1H-pyrazole-5-carboxylic acid (52.8 mg, 377 mmol, 1.20 equiv.) and ethyl 3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopyrrolidine-3-carboxylate (130 mg, 314 mmol, 1.00 equiv.) in pyridine (6.00 mL) was added EDCI (180 mg, 94.14 mmol, 3.00 equiv.). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with water and extracted with DCM. The combined organic layers were washed with brine and diluted with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave ethyl 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopyrrolidine-3-carboxylate (150 mg, crude) as a white solid.

[0392] [ka]

[0393] To a solution of ethyl 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopyrrolidine-3-carboxylate (140 mg, 261 mmol, 1.00 equiv.) in MeOH (3.00 mL) and water (1.00 mL) was added NaOH (52.2 mg, 1.31 mmol, 5.00 equiv.). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was washed with EtOAc. The pH of the aqueous phase was adjusted to 3 with 1 M aqueous HCl and extracted with EtOAc. The combined organic layers were washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopyrrolidine-3-carboxylic acid (100 mg, crude) as a white solid.

[0394] [ka]

[0395] To a solution of 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopyrrolidine-3-carboxylic acid (100 mg, 197 mmol, 1.00 equiv.) in DMSO (8.00 mL) was added NaCl (34.5 mg, 591 mmol, 3.00 equiv.). The reaction mixture was stirred at 130° C. for 1 h. The reaction mixture was diluted with water and extracted with DCM. The combined organic layers were washed with brine and extracted with anhydrous Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered, and concentrated under reduced pressure. The resulting residue was purified by prep-HPLC (neutral conditions; column: Waters Xbridge (150×25 mm, 5 um); mobile phase: [water (NH 4 N-((1S)-cycloheptyl(6-((2-oxopyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (57.0 mg, crude) was obtained as a white solid. The title compound was purified by chiral SFC (column: Daiel Chiralpak IG (250 mm × 30 mm, 10 mm); mobile phase: [ACN / MeOH (0.1%NH 3 H 2 O)]; B%: 60%-60%, 3.6 min); isolated as the second eluting single stereoisomer (17.3 mg, 36.1 mmol, 31% yield) as a white solid. LCMS [M+H] + =464.4m / z.

[0396] Example 8: Preparation of Compounds 5 and 6

[0397] [ka]

[0398] N-((1S)-cycloheptyl(6-(((5S)-2-oxo-5-(trifluoromethyl)pyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compounds 5 and 6).

[0399] [ka]

[0400] To a solution of methyl (5S)-3-((6-aminopyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (300 mg, 694 mmol, 1.00 equiv., TFA salt) in THF (5.00 mL) was added benzyl (S)-(3-bromo-1-cycloheptyl-2-oxopropyl)carbamate (Int.3; 397 mg, 1.04 mmol, 1.50 equiv.), trimethylborate (360 mg, 3.47 mmol, 391 mL, 5.00 equiv.), and DIEA (448 mg, 3.47 mmol, 604 mL, 5.00 equiv.). The reaction mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with NaCO 3 Wash with a saturated aqueous solution of anhydrous Na 2 SO 4 The resulting residue was purified by prep-TLC (SiO 2 , DCM / MeOH) to give methyl (5S-3-((2-((S)-(((benzyloxy)carbonyl)amino)(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (250 mg, 415 mmol, 60% yield) as a white solid. LCMS [M+H] + =602.3m / z.

[0401] [ka]

[0402] To a solution of methyl (5S-3-((2-((S)-(((benzyloxy)carbonyl)amino)(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (250 mg, 415 mmol, 1.00 equiv) in THF (5.00 mL) was added N 2 Pd / C (25.0 mg, purity 10.0%) was added under atmospheric pressure. The suspension was degassed and diluted with H 2 The reaction mixture was purged three times with H 2 The mixture was stirred at room temperature under (15 psi) for 2 h. The reaction mixture was filtered through a pad of Celite with MeOH and concentrated under reduced pressure to give methyl (5S)-3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (180 mg, 385 mmol, 93% yield) as a white solid. LCMS [M+H] + =468.4m / z.

[0403] [ka]

[0404] To a solution of methyl (5S)-3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (180 mg, 385 mmol, 1.00 equiv.) and 1-ethyl-1H-pyrazole-5-carboxylic acid (80.9 mg, 577 mmol, 1.50 equiv.) in pyridine (5.00 mL) was added EDCI (221 mg, 1.16 mmol, 3.00 equiv.). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with NaCO 3 Wash with a saturated aqueous solution of anhydrous Na 2 SO 4 The resulting residue was purified by prep-TLC (SiO2 , DCM / MeOH) to give methyl (5S)-3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (130 mg, 220 mmol, 57% yield) as a white solid. LCMS [M+H] + =590.3m / z.

[0405] [ka]

[0406] A solution of methyl (5S)-3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (130 mg, 220 mmol, 1.00 equiv) in THF (4.00 mL) was added to the reaction mixture with LiOH·H in water (1.00 mL). 2 0 (55.5 mg, 1.32 mmol, 6.00 equiv) was added at 0° C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water and 1 M aqueous HCl was added to adjust the pH to 2. The mixture was extracted with DCM. The combined organic layers were washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure afforded (5S)-3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (120 mg, 208 mmol, 95% yield) as a white solid. LCMS [M+H] + =576.4m / z.

[0407] [ka]

[0408] To a solution of (5S)-3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (120 mg, 208 mmol, 1.00 equiv.) in DMSO (5.00 mL) was added NaCl (60.9 mg, 1.04 mmol, 5.00 equiv.). The reaction mixture was stirred at 120° C. for 2 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with NaCO 3 Wash with a saturated aqueous solution of anhydrous Na 2 SO 4 The resulting residue was purified by prep-TLC (SiO 2 , DCM / MeOH) to give N-((1S)-cycloheptyl(6-(((5S)-2-oxo-5-(trifluoromethyl)pyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. LCMS [M+H] + =532.4m / z.

[0409] Compound 5: The title compound was purified by chiral SFC (column: Daicel Chiralcel OJ-H (250 mm × 30 mm, 5 mm); mobile phase: [0.1% NH 3 H 2 0]; B%: 20% to 20%, 2.0 min); isolated as the first eluting single stereoisomer (40.9 mg, 75.8 mmol, 56% yield) as a white solid. LCMS [M+H] + =532.5m / z.

[0410] Compound 6: The title compound was purified by chiral SFC (column: Daicel Chiralcel OJ-H (250 mm × 30 mm, 5 mm); mobile phase: [0.1% NH 3 H 2 0]; B%: 20% to 20%, 2.0 min); isolated as the second eluting single stereoisomer (14.6 mg, 26.9 mmol, 20% yield) as a white solid. LCMS [M+H]+ =532.5m / z.

[0411] Example 9: Preparation of Compound 7

[0412] [ka]

[0413] N-((1S)-(4,4-difluorocyclohexyl)(6-(((5S)-2-oxo-5-(trifluoromethyl)pyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compound 7).

[0414] [ka]

[0415] To a solution of methyl 6-aminopyridazine-3-carboxylate (10.0 g, 65.3 mmol, 1.00 equiv) in DCM (100 mL) was added di-tert-butyl dicarbonate (42.7 g, 195 mmol, 45.0 mL, 3.00 equiv), 4-dimethylaminopyridine (3.99 g, 32.6 mmol, 0.50 equiv) and DIEA (33.7 g, 261 mmol, 45.5 mL, 4.00 equiv) at 0° C. The reaction mixture was stirred at 15° C. for 12 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by column chromatography (SiO 2 , PE / EtOAc) to give methyl 6-(bis(tert-butoxycarbonyl)amino)pyridazine-3-carboxylate (18 g, 50.94 mmol, 78% yield) as a white solid. 1 H NMR (400 MHz, CDCl 3 )d 8.21(d,J=8.8Hz,1H),7.85(d,J=8.8Hz,1H),4.08(s,3H),1.50(s,18H). LCMS[M+H] + =354.3m / z.

[0416] [ka]

[0417] A solution of methyl 6-(bis(tert-butoxycarbonyl)amino)pyridazine-3-carboxylate (19.5 g, 55 mmol, 1.00 equiv) in THF (150 mL) and water (50.0 mL) was added with LiOH H 2 2H2O (4.63 g, 110 mmol, 2.00 equiv) was added at 0° C. The reaction mixture was stirred at 20° C. for 12 h. The reaction mixture was diluted with 1M HCl to adjust the pH to 5 and extracted with EtOAc. The combined organic layers were washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure gave 6-((tert-butoxycarbonyl)amino)pyridazine-3-carboxylic acid (12.0 g, 50.1 mmol, 91% yield) as a white solid. 1 H NMR (400 MHz, CDCl 3 )d 8.55-8.48(m,1H),8.41-8.20(m,1H),8.18-7.95(m,1H),1.58(s,9H). LCMS[M+Na] + =262.0 m / z.

[0418] [ka]

[0419] To a solution of 6-((tert-butoxycarbonyl)amino]pyridazine-3-carboxylic acid (12.0 g, 50.1 mmol, 1.00 equiv.) in THF (480 mL) was added 1,1'-carbonyldiimidazole (24.4 g, 150 mmol, 3.00 equiv.). The resulting mixture was stirred at 20 °C for 2 h and then cooled to 0 °C. NaBH 4 (4.74 g, 125 mmol, 2.50 equiv.) was added dropwise. The reaction mixture was further stirred at 20° C. for 2 h. The reaction mixture was cooled to 0° C. and diluted with NH 4 The mixture was diluted with a saturated aqueous solution of Cl and extracted with EtOAc. The combined organic layers were washed with anhydrous Na 2 SO4 The mixture was dried over 1000 ml of ethyl acetate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO 2 , PE / EtOAc) to give tert-butyl (6-(hydroxymethyl)pyridazin-3-yl)carbamate (5.00 g, 22.2 mmol, 44% yield) as a white solid. 1 H NMR (400 MHz, CDCl 3 )d 8.25(d,J=9.2Hz,1H),7.67(s,1H),7.49(d,J=9.2Hz,1H),4.91(s,2H),1.55(s,9H). LCMS[M+H] + =226.1m / z.

[0420] [ka]

[0421] A solution of tert-butyl (6-(hydroxymethyl)pyridazin-3-yl)carbamate (3.00 g, 13.3 mmol, 1.00 equiv) and thionyl chloride (3.17 g, 26.6 mmol, 1.93 mL, 2.00 equiv) in DCM (30.0 mL) was stirred for 1 h at 0° C. The reaction mixture was concentrated under reduced pressure to give tert-butyl (6-(chloromethyl)pyridazin-3-yl)carbamate (3.00 g, 12.3 mmol, 92% yield) as a yellow solid.

[0422] [ka]

[0423] To a solution of tert-butyl(6-(chloromethyl)pyridazin-3-yl)carbamate (1.00 g, 4.10 mmol, 1.00 equiv.) and 1-(tert-butyl)3-methyl(5S)-2-oxo-5-(trifluoromethyl)pyrrolidine-1,3-dicarboxylate (2.11 g, 6.77 mmol, 1.10 equiv.) in DMF (10.0 mL) was added Cs 2 CO 3(4.01 g, 12.3 mmol, 2.00 equiv.) was added. The reaction mixture was stirred at 55° C. for 2 h. The reaction mixture was diluted with NaCO 3 Dilute with a saturated aqueous solution of ethyl acetate, extract with EtOAc, and 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO 2 , PE / EtOAc) to give 1-(tert-butyl) 3-methyl(5S)-3-((6-((tert-butoxycarbonyl)amino)pyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-1,3-dicarboxylate (1.30 g, 2.31 mmol, 61% yield) as a white solid. LCMS [M+H] + =519.3m / z.

[0424] [ka]

[0425] A solution of 1-(tert-butyl) 3-methyl (5S)-3-((6-((tert-butoxycarbonyl) amino) pyridazin-3-yl) methyl)-2-oxo-5-(trifluoromethyl) pyrrolidine-1,3-dicarboxylate (1.00 g, 1.93 mmol, 1.00 equiv) and TFA (1.10 g, 9.64 mmol, 714 mL, 5.00 equiv) in DCM (10.0 mL) was stirred at 15° C. for 2 h. The reaction mixture was concentrated under reduced pressure to give methyl (5S)-3-((6-aminopyridazin-3-yl) methyl)-2-oxo-5-(trifluoromethyl) pyrrolidine-3-carboxylate (810 mg, 1.87 mmol, 97% yield, TFA salt) as a yellow oil. LCMS [M+H] + =319.1m / z.

[0426] [ka]

[0427] To (5S)-3-((6-aminopyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (270 mg, 624 mmol, 1.00 equiv, TFA salt) and benzyl (S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate (Int.2; 379 mg, 937 mmol, 1.50 equiv) in THF (2.00 mL) was added DIEA (403 mg, 3.12 mmol, 544 mL, 5.00 equiv) and trimethylborate (324 mg, 3.12 mmol, 352 mL, 5.00 equiv). The reaction mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with NaCO 3 Dilute with a saturated aqueous solution of ethyl acetate, extract with EtOAc, and 2 SO 4 The resulting residue was purified by prep-TLC (SiO 2 , DCM / MeOH) to give methyl (5S)-3-((2-((S)-(((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (200 mg, 481 mmol, 51% yield) as a yellow solid. LCMS [M+H] + =624.2m / z.

[0428] [ka]

[0429] To a solution of methyl (5S)-3-((2-((S)-(((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (200 mg, 481 mmol, 1.00 equiv) in THF (10.0 mL) was added N 2 Pd / C (50.0 mg, 10% purity) was added under vacuum. The suspension was degassed under vacuum and diluted with H 2 The reaction mixture was purged with H2 The mixture was stirred under (15 psi) at 15° C. for 12 h. The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to give methyl (5S)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (130 mg, 265 mmol, 83% yield) as a yellow solid. LCMS [M+H] + =490.3m / z.

[0430] [ka]

[0431] To a solution of methyl (5S)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (130 mg, 265 mmol, 1.00 equiv.) and 1-ethyl-1H-pyrazole-5-carboxylic acid (55.8 mg, 398 mmol, 1.50 equiv.) in pyridine (5.00 mL) was added EDCI (101 mg, 531 mmol, 2.00 equiv.). The reaction mixture was stirred at 15° C. for 2 h. The reaction mixture was diluted with NaCO 3 The mixture was diluted with a saturated aqueous solution of ethyl acetate and extracted with EtOAc. The combined organic layers were washed with anhydrous Na 2 SO 4 Drying at 40° C., filtration and concentration under reduced pressure gave a residue which was purified by prep-TLC (SiO 2 , DCM / MeOH) to give methyl (5S)-3-((2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-(pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (120 mg, 196 mmol, 74% yield) as a yellow solid. LCMS [M+H] + =612.3m / z.

[0432] [ka]

[0433] To a solution of methyl (5S)-3-((2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (120 mg, 196 mmol, 1.00 equiv) in THF (5.00 mL) and water (5.00 mL), LiOH·H 2 2H2O (16.4 mg, 392 mmol, 2.00 equiv) was added at 0° C. The reaction mixture was stirred at 15° C. for 2 h. The reaction mixture was acidified with 1 M aqueous HCl to pH=4, and then extracted with EtOAc. The organic layer was washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure afforded (5S)-3-((2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (100 mg, 167 mmol, 85% yield) as a yellow solid. LCMS [M+H] + =598.3m / z.

[0434] [ka]

[0435] To a solution of (5S)-3-((2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (100 mg, 167 mmol, 1.00 equiv.) in DMSO (5.00 mL) was added NaCl (19.5 mg, 334 mmol, 2.00 equiv.). The reaction mixture was stirred at 120° C. for 2 h. The reaction mixture was diluted with water, extracted with EtOAc and washed with anhydrous Na2 SO 4 Drying at 40° C., filtration and concentration under reduced pressure gave a residue which was purified by prep-TLC (SiO 2 , DCM / MeOH) to give N-((1S)-(4,4-difluorocyclohexyl)(6-(((5S)-2-oxo-5-(trifluoromethyl)pyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. The title compound was purified using chiral SFC (column: Daicel Chiralcel OJ (250 mm x 50 mm, 10 mm); mobile phase: [0.1% NH in IPA]. 3 H 2 0]; B%: 20% to 20%, 2.5 min); isolated as the second eluting single stereoisomer (17.53 mg, 28.79 mmol, 53% yield) as a white solid. LCMS [M+H] + =554.3m / z.

[0436] Example 10: Preparation of Compound 8

[0437] [ka]

[0438] N-((1S)-2,2-dicyclopropyl-1-(6-(((5S)-2-oxo-5-(trifluoromethyl)pyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)ethyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compound 8).

[0439] [ka]

[0440] To a solution of methyl (5S)-3-((6-aminopyridazin-3-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (300 mg, 694 μmol, 1.00 equiv., TFA salt) in THF (5 mL) was added (S)-(4-bromo-1,1-dicyclopropyl-3-oxobutan-2-yl)carbamate (Int.1; 395 mg, 1.04 mmol, 1.50 equiv.), B(OMe). 3 (360 mg, 3.47 mmol, 391 μL, 5.00 equiv.), and DIPEA (448 mg, 3.47 mmol, 604 μL, 5.00 equiv.) were added. The mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with H 2 The mixture was diluted with O and extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO 3 Wash with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO 2 , DCM:MeOH=10:1), methyl (5S)-3-((2-((S)-1-(((benzyloxy)carbonyl)amino)-2,2-dicyclopropylethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (250 mg, 416 μmol, 60% yield) was obtained as a white solid. LCMS [M+H] + =600.3 m / z.

[0441] [ka]

[0442] To methyl (5S)-3-((2-((S)-1-(((benzyloxy)carbonyl)amino)-2,2-dicyclopropylethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (250 mg, 416 μmol, 1.00 equiv) in THF (5.00 mL), 2 Pd / C (25.0 mg, 10.0% purity) was added under atmospheric pressure. The suspension was degassed and2 The mixture was purged with H 2 The mixture was stirred at room temperature under (15 psi) for 2 h. The reaction mixture was filtered, the filter cake was washed with MeOH, and the filtrate was concentrated under reduced pressure to give methyl (5S)-3-((2-((S)-1-amino-2,2-dicyclopropylethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (150 mg, 322 μmol, 77% yield) as a white solid.

[0443] [ka]

[0444] To a solution of methyl (5S)-3-((2-((S)-1-amino-2,2-dicyclopropylethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (150 mg, 322 μmol, 1.00 equiv.) and 1-ethyl-1H-pyrazole-5-carboxylic acid (67.7 mg, 483 μmol, 1.50 equiv.) in pyridine (5.00 mL) was added EDCI (185 mg, 966 μmol, 3.00 equiv.). The mixture was stirred at room temperature for 2 h. The reaction mixture was cooled to 5° C. for 2 h and cooled to 5° C. for 2 h. 2 The mixture was diluted with O and extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO 3 Wash with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO 2 , DCM:MeOH=10:1), methyl (5S)-3-((2-((S)-2,2-dicyclopropyl-1-(1-ethyl-1H-pyrazole-5-carboxamido)ethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (130 mg, 221 μmol, 69% yield) was obtained as a white solid. LCMS [M+H] + =588.3m / z.

[0445] [ka]

[0446] To a solution of methyl (5S)-3-((2-((S)-2,2-dicyclopropyl-1-(1-ethyl-1H-pyrazole-5-carboxamido)ethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylate (130 mg, 221 μmol, 1.00 equiv) in THF (4.00 mL) was added H 2 LiOH H in O (1.00 mL) 2 O (55.7 mg, 1.33 mmol, 6.00 equiv) was added at 0° C. The mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with H 2 The mixture was diluted with O and 1M HCl was added to adjust the pH to 2. The mixture was then extracted with DCM and the combined organic layers were washed with Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure afforded (5S)-3-((2-((S)-2,2-dicyclopropyl-1-(1-ethyl-1H-pyrazole-5-carboxamido)ethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (120 mg, 209 μmol, 95% yield) as a white solid. LCMS [M+H] + =574.4m / z.

[0447] [ka]

[0448] To a solution of (5S)-3-((2-((S)-2,2-dicyclopropyl-1-(1-ethyl-1H-pyrazole-5-carboxamido)ethyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (120 mg, 209 μmol, 1.00 equiv.) in DMSO (2.00 mL) was added NaCl (61.1 mg, 1.05 mmol, 5.00 equiv.). The mixture was stirred at 120° C. for 2 h. The reaction mixture was diluted with H 2 The mixture was diluted with O and extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO 3 Wash with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO 2 , DCM:MeOH=10:1), N-((1S)-2,2-dicyclopropyl-1-(6-(((5S)-2-oxo-5-(trifluoromethyl)pyrrolidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)ethyl)-1-ethyl-1H-pyrazole-5-carboxamide (87.1 mg, 159 μmol, 76% yield) was obtained as a mixture of two isomers, which was obtained as a white solid. The mixture of isomers was then further purified by SFC (column: DAICEL CHIRALCEL OJ-H (250 mm*30 mm, 5 μm); mobile phase: [0.1% NH 3 / H 2 O EtOH]; B%: 20% to 20%, 2.2 min, Rt=0.865, 0.991 min). The second eluting single isomer (47.4 mg, 85.8 μmol, 54% yield) was obtained as a white solid. LCMS [M+H] + =530.4m / z.

[0449] Example 11: Preparation of Compounds 9 and 10

[0450] [ka]

[0451] N-((1S)-cycloheptyl(6-((5,5-difluoro-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compounds 9 and 10).

[0452] [ka]

[0453] To a solution of tert-butyl (6-(chloromethyl)pyridazin-3-yl)carbamate (0.200 g, 821 μmol, 1.00 equiv.) in DMF (4.00 mL) was added Cs 2 CO 3 (535 mg, 1.64 mmol, 2.00 equiv.) and 1-(tert-butyl) 3-methyl 5,5-difluoro-2-oxopiperidine-1,3-dicarboxylate (289 mg, 985 μmol, 1.20 equiv.) were added. The mixture was stirred at 70° C. for 2 h. The reaction mixture was stirred at H 2 The mixture was diluted with O and extracted with EtOAc. The combined organic layers were washed with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO 2 , PE / EtOAc=1:1), 1-(tert-butyl) 3-methyl 3-((6-((tert(butoxycarbonyl)amino)pyridazin-3-yl)methyl)-5,5-difluoro-2-oxopiperidine-1,3-dicarboxylate (0.220 g, 440 μmol, 54% yield) was obtained as a white solid. LCMS [M+H] + =501.3m / z.

[0454] [ka]

[0455] To a solution of 1-(tert-butyl) 3-methyl 3-((6-((tert-butoxycarbonyl)amino)pyridazin-3-yl)methyl)-5,5-difluoro-2-oxopiperidine-1,3-dicarboxylate (0.200 g, 400 μmol, 1.00 equiv.) in DCM (3.00 mL) was added TFA (456 mg, 4.00 mmol, 296 μL, 10.0 equiv.). The mixture was stirred at 15° C. for 3 h. The reaction mixture was concentrated under reduced pressure to give methyl 3-((6-aminopyridazin-3-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.160 g, 386 μmol, 97% yield, TFA salt) as a yellow oil, which was used directly in the next step. LCMS [M+H] + =301.1 m / z.

[0456] [ka]

[0457] To a solution of methyl 3-((6-aminopyridazin-3-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.160 g, 386 μmol, 1.00 equiv., TFA salt) and benzyl (S)-(3-bromo-1-cycloheptyl-2-oxopropyl)carbamate (Int.3; 221 mg, 579 μmol, 1.50 equiv.) in THF (5.00 mL) was added B(OMe). 3 (201 mg, 1.93 mmol, 218 μL, 5.00 equiv) and DIPEA (399 mg, 3.09 mmol, 538 μL, 8.00 equiv) were added. The mixture was stirred at 70° C. for 1 h. The reaction mixture was diluted with H 2 The mixture was diluted with O and extracted with EtOAc. The combined organic layers were washed with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO 2, DCM:MeOH=10:1), affording methyl 3-((2-((S)-(((benzyloxy)carbonyl)amino)(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.200 g, 343 μmol, 89% yield) as a yellow solid. LCMS [M+H] + =584.2m / z.

[0458] [ka]

[0459] A mixture of methyl 3-((2-((S)-(((benzyloxy)carbonyl)amino)(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.150 g, 257 μmol, 1.00 equiv.) and Pd / C (0.100 g, 10.0% purity) in THF (3.00 mL) was degassed and diluted with H 2 (15 psi) three times, then H 2 The mixture was stirred at 15° C. under (15 psi) for 2 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give methyl 3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.110 g, 245 μmol, 95% yield) as a yellow solid. LCMS [M+Na] + =450.3m / z.

[0460] [ka]

[0461] To a solution of methyl 3-((2-((S)-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.110 g, 245 μmol, 1.00 equiv.) in pyridine (3.00 mL) was added EDCI (141 mg, 734 μmol, 3.00 equiv.) and 1-ethyl-1H-pyrazole-5-carboxylic acid (51.4 mg, 367 μmol, 1.50 equiv.). The mixture was stirred at 15° C. for 1 h. The reaction mixture was cooled to 10° C. and cooled to 37° C. for 1 h. 2 The mixture was diluted with O and extracted with EtOAc. The combined organic layers were washed with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO 2 , DCM:MeOH=10:1), to give methyl 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.110 g, 192 μmol, 79% yield) as a white solid. LCMS [M+H] + =572.4m / z.

[0462] [ka]

[0463] THF (3.00 mL) and H 2 A solution of methyl 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylate (0.110 g, 192 μmol, 1.00 equiv) in 2HO (1.00 mL) was added with LiOH H 20 (24.2 mg, 577 μmol, 3.00 equiv.) was added. The mixture was stirred at 15° C. for 1 h. The pH of the reaction mixture was adjusted to 4 with 1 M HCl at 0° C. and concentrated under reduced pressure to give the crude product, 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylic acid, which was used directly in the next step.

[0464] [ka]

[0465] To a solution of crude 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-5,5-difluoro-2-oxopiperidine-3-carboxylic acid from the previous step in DMSO (3.00 mL) was added NaCl (31.4 mg, 538 μmol, 3.00 equiv.). The mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to 100° C. for 1 h. 2 The mixture was diluted with O and extracted with EtOAc. The combined organic layers were washed with H 2 Wash with O and Na 2 SO 4 The mixture was dried at 40° C., filtered and concentrated under reduced pressure to give a mixture of diastereomers of N-((1S)-cycloheptyl(6-((5,5-difluoro-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (0.045 g, 84.9 μmol, 44% yield for two steps) as a white solid. The residue was purified by SFC (column: DAICEL CHIRALPAK AS (250 mm*30 mm, 10 μm); mobile phase: [0.1% NH 3 / H 2 O MeOH]; B%: 35%-35%, 4.8 min, Rt = 1.468, 1.614 min) to give the isolated title compound as a single isomer.

[0466] Compound 9: The title compound was obtained as the first eluting single stereoisomer from SFC purification (15.0 mg, 29.2 μmol, 38% yield) as a yellow solid. LCMS [M+H]+=514.4 m / z.

[0467] Compound 10: The title compound was obtained as the second eluting single stereoisomer from SFC purification (15.0 mg, 29.2 μmol, 38% yield) as a yellow solid. LCMS [M+H] + =514.4m / z.

[0468] Example 12: Preparation of Compounds 11 and 12

[0469] [ka]

[0470] N-((1S-cycloheptyl(6-((2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compounds 11 and 12).

[0471] [ka]

[0472] To a solution of methyl 3-((2-((S-amino(cycloheptyl)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (120 mg, 290 mmol, 1.00 equiv.) and 1-ethyl-1H-pyrazole-5-carboxylic acid (48.8 mg, 348 mmol, 1.20 equiv.) in pyridine (5.00 mL) was added EDCI (166 mg, 870 mmol, 3.00 equiv.). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were diluted with NaCO 3 Wash with a saturated aqueous solution of anhydrous Na 2 SO 4The resulting residue was purified by prep-TLC (SiO 2 , DCM / MeOH) to give methyl 3-((2-((S-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (100 mg, 186 mmol, 64% yield) as a white solid. LCMS [M+H] + =536.2m / z.

[0473] [ka]

[0474] A solution of methyl 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylate (100 mg, 186 mmol, 1.00 equiv) in THF (3.00 mL) was added to the reaction mixture with LiOH·H in water (1.00 mL). 2 0 (47.0 mg, 1.12 mmol, 6.00 equiv.) was added. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was acidified to pH=2 by adding 1M aqueous HCl. The reaction mixture was extracted with DCM. The combined organic layers were washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and concentrating under reduced pressure afforded 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylic acid (90.0 mg, 172 mmol, 92% yield) as a white solid. LCMS [M+H] + =522.4m / z.

[0475] [ka]

[0476] To a solution of 3-((2-((S)-cycloheptyl(1-ethyl-1H-pyrazole-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxopiperidine-3-carboxylic acid (90.0 mg, 172 mmol, 1.00 equiv.) in DMSO (5.00 mL) was added NaCl (50.4 mg, 862 mmol, 5.00 equiv.). The reaction mixture was stirred at 80° C. for 1 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with NaCO 3 Wash with a saturated aqueous solution of anhydrous Na 2 SO 4 The resulting residue was purified by prep-TLC (SiO 2 , DCM / MeOH), to give N-((1S)-cycloheptyl(6-((2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (59.2 mg, 122 mmol, 71% yield) as a white solid. LCMS [M+H] + =478.4m / z.

[0477] Compound 11: The title compound was purified by chiral SFC (column: Daicel Chiralpak AD (250 mm × 30 mm, 10 mm); mobile phase: [0.1% NH 3 H 2 0]; B%: 40% to 40%, 3.16 min); isolated as the first eluting single stereoisomer (23.0 mg, 47.3 mmol, 40% yield) as a white solid. LCMS [M+H] + =478.4m / z.

[0478] Compound 12: The title compound was purified by chiral SFC (column: Daicel Chiralpak AD (250 mm × 30 mm, 10 mm); mobile phase: [0.1% NH 3 H 2 0]; B%: 40% to 40%, 3.16 min); isolated as the second eluting single stereoisomer (22.3 mg, 46.1 mmol, 39% yield) as a white solid. LCMS [M+H] +=478.4m / z.

[0479] Example 13: Preparation of Compound 13

[0480] [ka]

[0481] N-((1S)-(4,4-difluorocyclohexyl)(6-((2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide. (Compound 13).

[0482] [ka]

[0483] To a solution of methyl 3-((6-aminopyridazin-3-yl)methyl)-2-oxop...

Claims

1. A compound represented by the structure of formula (I): 【Chemistry 1】 or a pharma- ceutically acceptable salt thereof, wherein: A is a 5- to 6-membered heteroaryl and C ３～６ carbocyclic rings, each of which is selected from ハロゲン、-OR １１ 、-SR １１ 、-N(R １１ ) ２ 、-C(O)R １１ 、-C(O)N(R １１ ) ２ 、-N(R １１ )C(O)R １１ 、-N(R １１ )S(O) ２ R １１ 、-C(O)OR １１ 、-OC(O)R １１ 、-S(O)R １１ 、-S(O) ２ R １１ 、-NO ２ 、-CN; Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN,C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～１０ Alkyl, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =N(R １１ ), and -CN, １～１０ Alkyl; and Halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), —CN; and halogen, —OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -NO ２ , =O, =N(R １１Ａ ), and —CN, optionally substituted with one or more substituents selected from １～１０ C optionally substituted with one or more substituents independently selected from alkyl, ３～１０ Carbocyclic ring; and optionally substituted with one or more substituents independently selected from: B is -C(H)(R ５ ) ２ and C ３～１０ carbocyclic rings, each C ３～１０ The carbocyclic ring is ハロゲン、-OR １２ 、-SR １２ 、-N(R １２ ) ２ 、-C(O)R １２ 、-C(O)N(R １２ ) ２ 、-N(R １２ )C(O)R １２ -N(R １２ )S(O) ２ R １２ 、-C(O)OR １２ 、-OC(O)R １２ 、-S(O)R １２ 、-S(O) ２ R １２ 、-NO ２ 、=O、=S、=N(R １２ )、-CN; C １～１０ Alkyl and C ３～１０ Carbocyclic rings, each of which is halogen, -OR １２ , -SR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -S(O)R １２ , -S(O) ２ R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN,C ３～１０ and optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -NO ２ , =O, =N(R １２ ), and -CN, １～１０ Alkyl and C ３～１０ Carbocyclic ring; and Each R ５ for each occurrence, (i), (ii), and (iii) of the following: (i)ハロゲン、-OR １３ 、-SR １３ 、-N(R １３ ) ２ 、-C(O)R １３ 、-C(O)N(R １３ ) ２ 、-N(R １３ )C(O)R １３ 、-N(R １３ )S(O) ２ R １３ 、-C(O)OR １３ 、-OC(O)R １３ 、-S(O)R １３ 、-S(O) ２ R １３ 、-NO ２ 、-CN; (ii) halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), C optionally substituted with one or more substituents independently selected from -CN １～１０ Alkyl; and (iii) C ３～１０ A carbocyclic ring, Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), -CN; and Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ C optionally substituted with one or more substituents independently selected from alkyl, ３～１０ Carbocyclic ring; are independently selected from Each R １ But every time it appears, ハロゲン、-OR １４ 、-SR １４ 、-N(R １４ ) ２ 、-C(O)R １４ 、-C(O)N(R １４ ) ２ 、-N(R １４ )C(O)R １４ 、-N(R １４ )S(O) ２ R １４ 、-C(O)OR １４ 、-OC(O)R １４ 、-S(O)R １４ 、-S(O) ２ R １４ 、-NO ２ 、=O、=S、=N(R １４ )、-CN; Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; and Halogen, -OR １４Ａ , -SR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -C(O)N(R １４Ａ ) ２ , -N(R １４Ａ ) C(O)R １４Ａ , -C(O)OR １４Ａ , -OC(O)R １４Ａ , -S(O)R １４Ａ , -S(O) ２ R １４Ａ , -NO ２ , =O, =S, =N(R １４Ａ ), —CN; and halogen, —OR １４Ａ , -SR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -C(O)N(R １４Ａ ) ２ , -N(R １４Ａ ) C(O)R １４Ａ , -C(O)OR １４Ａ , -OC(O)R １４Ａ , -S(O)R １４Ａ , -S(O) ２ R １４Ａ , -NO ２ , =O, =S, =N(R １４Ａ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ C optionally substituted with one or more substituents independently selected from alkyl, ３～１０ Carbocyclic ring; or Two R's １ The substituents taken together form C ３～６ can form a carbocyclic ring, ３～６ The carbocyclic ring is Halogen, -OR １８Ａ , -N(R １８Ａ ) ２ , -C(O)R １８Ａ , -C(O)N(R １８Ａ ) ２ , -NO ２ , =O, =S, =N(R １８Ａ ), -CN; and Halogen, -OR １８Ａ , -N(R １８Ａ ) ２ , -C(O)R １８Ａ , -C(O)N(R １８Ａ ) ２ , -NO ２ , =O, =S, =N(R １８Ａ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; and R ２ but, Hydrogen, halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -N(R １５ ) S (O) ２ R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , -CN; and Halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , =O, =S, =N(R １５ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; is selected from Each R ３ But every time it appears, Hydrogen, halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , -CN; and Halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; are independently selected from Each R ４ But every time it appears, halogen, -OR １７ , -SR １７ , -N(R １７ ), ２ , -C(O)R １７ , -C(O)N(R １７ ), ２ , -N(R １７ ),C(O)R １７ , -N(R １７Ａ ),C(O)R １７Ａ , -N(R １７ ),S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN; and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ and -CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; are independently selected from R １１ , R １１Ａ , R １２ , R １３ , R １４ , R １４Ａ , R １５ , R １６ , R １７ , R １７Ａ , and R １８Ａ But for each occurrence, hydrogen; Halogen, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , =O, -CN, C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～６ Alkyl, each C ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from the group consisting of halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , ═O, and —CN; １～６ Alkyl; and Halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２ , -NO ２ , ═O, and —CN, optionally substituted with one or more substituents independently selected from ３～１０ Carbocycles and 3- to 10-membered heterocycles; are independently selected from n is selected from 1 and 2; m is selected from 0, 1, and 2; A compound, or a pharma- ceutically acceptable salt thereof, wherein p is selected from 0, 1, 2, 3, 4, 5, and 6.

2. A is a 5- to 6-membered heteroaryl and C ３～６ carbocyclic rings, each of which is selected from Halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), -CN; and Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -NO ２ , =O, =N(R １１Ａ ), and —CN, optionally substituted with one or more substituents selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ 10. The compound or salt of claim 1, optionally substituted with one or more substituents independently selected from carbocycles.

3. A is a 5-6 membered heteroaryl; Halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), -CN; and Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -NO ２ , =O, =N(R １１Ａ ), and —CN, optionally substituted with one or more substituents selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ 3. The compound or salt of claim 2 which is a 5-6 membered heteroaryl optionally substituted with one or more substituents independently selected from carbocycles.

4. A is a 5-membered heteroaryl; Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -NO ２ , -CN; and Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -NO ２ and -CN, optionally substituted with one or more substituents selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ 4. The compound or salt of claim 3 which is a 5-membered heteroaryl optionally substituted with a carbocyclic ring.

5. A is halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～６ 5. A compound or salt according to claim 4 selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, optionally substituted with cycloalkyl.

6. A, 【Chemistry 2】 6. The compound or salt of claim 5, selected from:

7. R １ But, C ３～１０ A carbocyclic ring, Halogen, -OR １４Ａ , -SR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -C(O)N(R １４Ａ ) ２ , -N(R １４Ａ ) C(O)R １４Ａ , -C(O)OR １４Ａ , -OC(O)R １４Ａ , -S(O)R １４Ａ , -S(O) ２ R １４Ａ , -NO ２ , =O, =S, =N(R １４Ａ ), -CN; and Halogen, -OR １４Ａ , -SR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -C(O)N(R １４Ａ ) ２ , -N(R １４Ａ ) C(O)R １４Ａ , -C(O)OR １４Ａ , -OC(O)R １４Ａ , -S(O)R １４Ａ , -S(O) ２ R １４Ａ , -NO ２ , =O, =S, =N(R １４Ａ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ The compound or salt of any one of claims 1 to 6 which is a carbocyclic ring.

8. R １ But, C ３～６ A carbocyclic ring, Halogen, -OR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -NO ２ , -CN; and Halogen, -OR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -NO ２ and -CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; C optionally substituted with one or more substituents independently selected from ３～６ 8. The compound or salt of claim 7 which is a carbocyclic ring.

9. R １ is halogen, -OR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～６ 9. The compound or salt of claim 8 which is cycloalkyl.

10. R １ but, 【Chemistry 3】 10. The compound or salt of claim 9,

11. Two R's １ The substituents taken together form C ３～６ can form a carbocyclic ring, ３～６ The carbocyclic ring is Halogen, -OR １８Ａ , -N(R １８Ａ ) ２ , -C(O)R １８Ａ , -C(O)N(R １８Ａ ) ２ , -NO ２ , =O, =S, =N(R １８Ａ ), -CN; and Halogen, -OR １８Ａ , -N(R １８Ａ ) ２ , -C(O)R １８Ａ , -C(O)N(R １８Ａ ) ２ , -NO ２ , =O, =S, =N(R １８Ａ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; 7. The compound or salt of any one of claims 1 to 6, optionally substituted with one or more substituents independently selected from:

12. Two R's １ The substituents taken together are halogen, -OR １８Ａ , -N(R １８Ａ ) ２ , -C(O)R １８Ａ , -C(O)N(R １８Ａ ) ２ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ haloalkyl, ３～６ 12. The compound or salt of claim 11, which is capable of forming a cycloalkyl.

13. Two R on adjacent carbon atoms １ The substituents taken together are halogen, -OR １８Ａ , -N(R １８Ａ ) ２ , -C(O)R １８Ａ , -C(O)N(R １８Ａ ) ２ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ haloalkyl, ３～６ 12. The compound or salt of claim 11, which is capable of forming a cycloalkyl.

14. Two R on different carbon atoms １ The substituents taken together are halogen, -OR １８Ａ , -N(R １８Ａ ) ２ , -C(O)R １８Ａ , -C(O)N(R １８Ａ ) ２ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ haloalkyl, ３～６ 12. The compound or salt of claim 11, which is capable of forming a cycloalkyl.

15. Formula (I) is a compound of formula (II): 【Chemistry 4】 or a pharma- ceutically acceptable salt thereof, wherein: A is a 5- to 6-membered heteroaryl and C ３～６ carbocyclic rings, each of which is selected from Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -C(O)OR １１ , -OC(O)R １１ , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , -CN; and Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN,C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～１０ Alkyl, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =N(R １１ ), and -CN, １～１０ Alkyl; and B is -C(H)(R ５ ) ２ and C ３～１０ carbocyclic rings, each C ３～１０ The carbocyclic ring is ハロゲン、-OR １２ 、-SR １２ 、-N(R １２ ) ２ 、-C(O)R １２ 、-C(O)N(R １２ ) ２ 、-N(R １２ )C(O)R １２ 、-N(R １２ )S(O) ２ R １２ 、-C(O)OR １２ 、-OC(O)R １２ 、-S(O)R １２ 、-S(O) ２ R １２ 、-NO ２ 、=O、=S、=N(R １２ )、-CN; C １～１０ Alkyl and C ３～１０ Carbocyclic rings, each of which is halogen, -OR １２ , -SR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -S(O)R １２ , -S(O) ２ R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN,C ３～１０ and optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -NO ２ , =O, =N(R １２ ), and -CN, １～１０ Alkyl and C ３～１０ Carbocyclic ring; and Each R ５ for each occurrence, (i), (ii), and (iii) of the following: (i)ハロゲン、-OR １３ 、-SR １３ 、-N(R １３ ) ２ 、-C(O)R １３ 、-C(O)N(R １３ ) ２ 、-N(R １３ )C(O)R １３ 、-N(R １３ )S(O) ２ R １３ 、-C(O)OR １３ 、-OC(O)R １３ 、-S(O)R １３ 、-S(O) ２ R １３ 、-NO ２ 、-CN; (ii) halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), C optionally substituted with one or more substituents independently selected from -CN １～１０ Alkyl; and (iii) C ３～１０ A carbocyclic ring, Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), -CN; and Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl, C optionally substituted with one or more substituents independently selected from ３～１０ Carbocyclic ring; are independently selected from Each R １ But every time it appears, Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -N(R １４ ) S (O) ２ R １４ , -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), -CN; and Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; are independently selected from R ２ but, Hydrogen, halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -N(R １５ ) S (O) ２ R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , -CN; and Halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , =O, =S, =N(R １５ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; is selected from Each R ３ Each occurrence represents hydrogen, halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , -CN; and halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ independently selected from alkyl, Each R ４ But every time it appears, Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN; and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; are independently selected from R １１ , R １２ , R １３ , R １４ , R １５ , R １６ , and R １７ But for each occurrence, hydrogen; Halogen, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , =O, -CN, C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～６ Alkyl, each C ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from the group consisting of halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , ═O, and —CN; １～６ Alkyl; and Halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２ , -NO ２ , ═O, and —CN, optionally substituted with one or more substituents independently selected from ３～１０ Carbocycles and 3- to 10-membered heterocycles; are independently selected from n is selected from 1 and 2; m is selected from 0, 1, and 2; 2. The compound or salt of claim 1, wherein p is selected from 0, 1, 2, 3, 4, 5, and 6.

16. 16. The compound or salt of claim 15, wherein n is 1.

17. The compound or salt of claim 15 or 16, wherein formula (II) is represented by the structure of formula (II-a): 【Chemistry 5】

18. 16. The compound or salt of claim 15, wherein n is 2.

19. The compound or salt of claim 15 or 18, wherein formula (II) is represented by the structure of formula (II-b): 【Chemistry 6】

20. A is a 5-membered heteroaryl; Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -CN; and Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -C.N., C. ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～６ Alkyl, ３～１０ The carbocycle and the 3- to 10-membered heterocycle are each -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ and -CN, １～６ Alkyl; 20. The compound or salt of any one of claims 15 to 19, which is a 5-membered heteroaryl optionally substituted with one or more substituents independently selected from:

21. A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any one of which is halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ and one or more C optionally substituted with one or more substituents independently selected from -CN. １～６ 21. The compound or salt of claim 20, optionally substituted with alkyl.

22. A is selected from pyrazolyl and oxadiazolyl, each of which is selected from halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -NO ２ and -CN, optionally substituted with one or more substituents independently selected from １～６ 22. The compound or salt of claim 21, optionally substituted with alkyl.

23. 23. The compound or salt of claim 22, wherein A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with methyl, ethyl, propyl, and isopropyl.

24. A, 【Chemistry 7】 24. The compound or salt of claim 23, selected from:

25. A is selected from thiophenyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any one of which is Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -CN; and Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -C.N., C. ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～６ Alkyl, ３～１０ The carbocycle and the 3- to 10-membered heterocycle are each -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ and -CN, optionally substituted with one or more substituents selected from １～６ Alkyl; 21. The compound or salt of claim 20, optionally substituted with one or more substituents independently selected from:

26. A is selected from thiophenyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, and triazolyl, any one of which is Halogen, -OR １１ , -N(R １１ ) ２ , -NO ２ , -CN; and Halogen, -OR １１ , -N(R １１ ) ２ , -NO ２ , -C.N., C. ３～６ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 6-membered heterocycle １～６ Alkyl; 26. The compound or salt of claim 25, optionally substituted with one or more substituents independently selected from:

27. A is selected from thiophenyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, and triazolyl, any one of which is -OR １１ , -N(R １１ ) ２ , -CN; and Halogen, -OR １１ , -N(R １１ ) ２ , and C ３～６ C optionally substituted with one or more substituents independently selected from cycloalkyl １～３ Alkyl; 27. The compound or salt of claim 26, optionally substituted with one or more substituents independently selected from:

28. A, 【Chemistry 8】 28. The compound or salt of claim 27, selected from:

29. A is C ３～６ A carbocyclic ring, Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -CN; and Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ and -CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; C optionally substituted with one or more substituents independently selected from ３～６ 20. The compound or salt of any one of claims 15 to 19 which is a carbocyclic ring.

30. Appropriately substituted C ３～６ The carbocyclic ring A is a spirocyclic ring C ４～６ Carbocyclic and bridged C ４～６ carbocyclic rings, each of which is selected from halogen, —OR １１ , -N(R １１ ) ２ - NO ２ , -C.N., C. １～６ Alkyl, and C １～６ 30. The compound or salt of claim 29, optionally substituted with one or more substituents independently selected from haloalkyl.

31. Ring A is 【Chemistry 9】 31. The compound or salt of claim 30,

32. B is -C(H)(R ５ ) ２ The compound or salt according to any one of claims 15 to 31,

33. -C(H)(R ５ ) ２ Each R ５ but, Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , -CN; Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; and Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN,C １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～１０ Carbocyclic ring; 27. The compound or salt of claim 26, independently selected from:

34. -C(H)(R ５ ) ２ Each R ５ is halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN,C １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～６ 34. The compound or salt of claim 33, independently selected from: carbocycle.

35. -CH(R ５ ) ２ but, 【Chemistry 10】 35. The compound or salt of claim 34,

36. -C(H)(R ５ ) ２ Each R ５ but, Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; and Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN,C １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～１０ Carbocyclic ring; 34. The compound or salt of claim 33, independently selected from:

37. -C(H)(R ５ ) ２ Each R ５ But, C １～６ Alkyl and C ３～６ carbocycles, each of which is independently selected from halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ 37. The compound or salt of claim 36, optionally substituted with one or more substituents independently selected from: -N, -C, -N-, and -CN.

38. -CH(R ５ ) ２ but, 【Chemistry 11】 38. The compound or salt of claim 37, selected from:

39. B is C ６～１０ A carbocyclic ring, Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN; and Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; C optionally substituted with one or more substituents independently selected from ６～１０ 32. The compound or salt of any one of claims 15 to 31, which is carbocyclic.

40. B is selected from cyclohexyl and cycloheptyl, both of which are Halogen, -OR １２ , N(R １２ ) ２ , -NO ２ , -CN; and Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; 40. The compound or salt of claim 39, optionally substituted with one or more substituents independently selected from:

41. B, 【Chemistry 12】 41. The compound or salt of claim 40, selected from:

42. B is a monocyclic C ３～７ Carbocyclic and bicyclic C ５～１０ carbocycles, each of which is selected from Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN; and Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ each optionally substituted with one or more substituents independently selected from -CN; １～６ Alkyl and C ３～１０ Carbocyclic ring; 32. The compound or salt of any one of claims 15 to 31, optionally substituted with one or more substituents independently selected from:

43. B is halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN,C １～６ Alkyl, C １～６ Haloalkyl, and C ３～６ a monocyclic C optionally substituted with one or more substituents independently selected from cycloalkyl; ３～７ 43. The compound or salt of claim 42, wherein said ring is selected from:

44. B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, any of which is selected from halogen, C １～６ Alkyl, C １～６ Haloalkyl, and C ３～６ 44. The compound or salt of claim 43, optionally substituted with one or more substituents independently selected from cycloalkyl.

45. B, 【Chemistry 13】 45. The compound or salt of claim 44, selected from:

46. B is halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN,C １～６ Alkyl, and C １～６ A bicyclic C optionally substituted with one or more substituents independently selected from haloalkyl ５～１０ 43. The compound or salt of claim 42, selected from carbocycles.

47. The bicyclic C ５～１０ B, a carbocyclic ring, is a fused ring C ５～１０ carbocyclic, bridged C ５～１０ Carbocyclic and spirocyclic C ５～１０ carbocyclic rings, any of which may be selected from halogen, C １～６ Alkyl, and C １～６ 47. The compound or salt of claim 46, optionally substituted with one or more substituents independently selected from haloalkyl.

48. The bicyclic C ５～１０ B, a carbocyclic ring, is a halogen atom, １～６ Alkyl, and C １～６ Optionally substituted with one or more substituents independently selected from haloalkyl ５～１０ 48. The compound or salt of claim 47, which is selected from carbocycles.

49. B, 【Chemistry 14】 49. The compound or salt of claim 48, selected from:

50. The bicyclic C ５～１０ B, a carbocyclic ring, is a halogen atom, １～６ Alkyl, and C １～６ Bridge C optionally substituted with one or more substituents independently selected from haloalkyl ５～１０ 48. The compound or salt of claim 47, which is selected from carbocycles.

51. B, 【Chemistry 15】 51. The compound or salt of claim 50,

52. The bicyclic C ５～１０ B, a carbocyclic ring, is a halogen atom, １～６ Alkyl, C １～６ A spirocyclic C optionally substituted with one or more substituents independently selected from haloalkyl ５～１０ 48. The compound or salt of claim 47, which is selected from carbocycles.

53. B, 【Chemistry 16】 53. The compound or salt of claim 52, selected from:

54. 54. The compound or salt according to any one of claims 15 to 53, wherein m is 0.

55. m is 1, R ４ but, Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN; and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ and -CN, optionally substituted with one or more substituents selected from １～１０ Alkyl; 54. The compound or salt according to any one of claims 15 to 53, selected from:

56. R ４ is halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -S(O) ２ R １７ , and -CN; R １７ But every time it appears, hydrogen; Halogen, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２ , -NO ２ , =O, -CN, C ３～６ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 6-membered heterocycle １～６ Alkyl, each C ３～６ carbocyclic and 3- to 6-membered heterocyclic rings; １～６ Alkyl; and Halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２ , -NO ２ , ═O, and —CN, optionally substituted with one or more substituents independently selected from ３～６ Carbocycles and 3- to 6-membered heterocycles; 56. The compound or salt of claim 55, selected from:

57. R ４ is -Cl, -CN, 【Chemistry 17】 57. The compound or salt of claim 56, selected from:

58. R ４ is halogen, -OR １７ and -CN, optionally substituted with one or more substituents independently selected from １～６ alkyl, R １７ However, for each occurrence, halogen, C １～６ Alkyl, and C １～６ 56. The compound or salt of claim 55, selected from haloalkyl.

59. R ４ But methyl, 【Chemistry 18】 59. The compound or salt of claim 58, selected from:

60. Each R ３ Each occurrence represents hydrogen, halogen, -OR １６ , -N(R １６ ) ２ , -NO ２ , -C.N., C. １～３ Alkyl, and C １～３ 60. The compound or salt of any one of claims 15 to 59, independently selected from haloalkyl.

61. Each R ３ 56. The compound or salt of claim 55, wherein is hydrogen.

62. Each R ３ Each occurrence represents hydrogen, methyl, ethyl, and 【Chemistry 19】 61. The compound or salt of claim 60, independently selected from:

63. R ２ The compound or salt according to any one of claims 15 to 62, wherein is hydrogen.

64. R ２ is hydrogen, C １～３ Alkyl, and C １～３ 63. The compound or salt of any one of claims 15 to 62, selected from haloalkyl.

65. 65. The compound or salt of any one of claims 15 to 64, wherein p is selected from 0, 1, 2, 3, and 4.

66. Each R １ Each occurrence is a halogen, -OR １４ , -N(R １４ ) ２ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ 66. The compound or salt of any one of claims 15 to 65, independently selected from haloalkyl.

67. Each R １ Each occurrence is represented by halogen and -CF ３ 67. The compound or salt of claim 66, independently selected from:

68. Each R １ However, for each occurrence, halogen, C １～６ Alkyl, or C １～６ 67. The compound or salt of claim 66, independently selected from haloalkyl.

69. Each R １ However, each occurrence is methyl, ethyl, 【Chemistry 20】 69. The compound or salt of claim 68, independently selected from:

70. Formula (I) 【Chemistry 21】 【Chemical 22】 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 【Chemistry 26】 【Chemical 27】 【Chemistry 28】 【Chemical 29】 【Chemistry 30】 【Chemistry 31】 【Chemistry 32】 【Chemical 33】 【Chemical 34】 or a pharma- ceutically acceptable salt thereof.

71. A compound represented by the structure of formula (III): 【Chemistry 35】 or a pharma- ceutically acceptable salt thereof, wherein: A is a 5- to 6-membered heteroaryl and C ３～６ carbocyclic rings, each of which is selected from ハロゲン、-OR １１ 、-SR １１ 、-N(R １１ ) ２ 、-C(O)R １１ 、-C(O)N(R １１ ) ２ 、-N(R １１ )C(O)R １１ 、-N(R １１ )S(O) ２ R １１ 、-C(O)OR １１ 、-OC(O)R １１ 、-S(O)R １１ 、-S(O) ２ R １１ 、-NO ２ 、-CN; Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN,C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～１０ Alkyl, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =N(R １１ ), and -CN, １～１０ Alkyl; and Halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), —CN; and halogen, —OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -NO ２ , =O, =N(R １１Ａ ), and —CN, optionally substituted with one or more substituents selected from １～１０ C optionally substituted with one or more substituents independently selected from alkyl ３～１０ Carbocyclic ring; and B is -C(H)(R ５ ) ２ and C ３～１０ carbocyclic rings, each C ３～１０ The carbocyclic ring is ハロゲン、-OR １２ 、-SR １２ 、-N(R １２ ) ２ 、-C(O)R １２ 、-C(O)N(R １２ ) ２ 、-N(R １２ )C(O)R １２ 、-N(R １２ )S(O) ２ R １２ 、-C(O)OR １２ 、-OC(O)R １２ 、-S(O)R １２ 、-S(O) ２ R １２ 、-NO ２ 、=O、=S、=N(R １２ )、-CN; C １～１０ Alkyl and C ３～１０ Carbocyclic rings, each of which is halogen, -OR １２ , -SR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -S(O)R １２ , -S(O) ２ R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN,C ３～１０ and optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -NO ２ , =O, =N(R １２ ), and -CN, １～１０ Alkyl and C ３～１０ Carbocyclic ring; and Each R ５ for each occurrence, (i), (ii), and (iii) of the following: (i)ハロゲン、-OR １３ 、-SR １３ 、-N(R １３ ) ２ 、-C(O)R １３ 、-C(O)N(R １３ ) ２ 、-N(R １３ )C(O)R １３ 、-N(R １３ )S(O) ２ R １３ 、-C(O)OR １３ 、-OC(O)R １３ 、-S(O)R １３ 、-S(O) ２ R １３ 、-NO ２ 、-CN; ())ハロゲン、? １３ 、++ １３ 、!() １３ ) ２ 、(()) １３ 、!()((R １３ ) ２ 、!() １３ )(()) １３ 、 -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), C optionally substituted with one or more substituents independently selected from -CN １～１０ Alkyl; and (iii) C １～１０ is an alkyl group, Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), -CN; and Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ Carbocyclic ring; are independently selected from Each R １ But every time it appears, Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -N(R １４ ) S (O) ２ R １４ , -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), -CN; and Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; are independently selected from R ２ but, Hydrogen, halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -N(R １５ ) S (O) ２ R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , -CN; and Halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , =O, =S, =N(R １５ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; is selected from Each R ３ But every time it appears, Hydrogen, halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , -CN; and Halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; or Each R ４ But every time it appears, Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN; and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ and -CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; are independently selected from R １１ , R １１Ａ , R １２ , R １３ , R １４ , R １５ , R １６ , and R １７ But for each occurrence, hydrogen; Halogen, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , =O, -CN, C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～６ Alkyl, each C ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from the group consisting of halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , ═O, and —CN; １～６ Alkyl; and Halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２ , -NO ２ , ═O, and —CN, optionally substituted with one or more substituents independently selected from ３～１０ Carbocycles and 3- to 10-membered heterocycles; are independently selected from n is selected from 1 and 2; m is selected from 0, 1, and 2; A compound, or a pharma- ceutically acceptable salt thereof, wherein p is selected from 0, 1, 2, 3, 4, 5, and 6.

72. A is a 5- to 6-membered heteroaryl and C ３～６ carbocyclic rings, each of which is selected from Halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), -CN; and Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -NO ２ , =O, =N(R １１Ａ ), and —CN, optionally substituted with one or more substituents selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ 72. The compound or salt of claim 71, optionally substituted with one or more substituents independently selected from carbocycles.

73. A, Halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), -CN; and Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ) ２ , -N(R １１Ａ ) C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -NO ２ , =O, =N(R １１Ａ ), and —CN, optionally substituted with one or more substituents selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ 73. The compound or salt of claim 72 which is a 5-6 membered heteroaryl optionally substituted with a carbocycle.

74. A is a 5-membered heteroaryl; Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -NO ２ , -CN; and Halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -NO ２ and -CN, optionally substituted with one or more substituents selected from １～１０ Alkyl; C optionally substituted with one or more substituents independently selected from ３～１０ 74. The compound or salt of claim 73 which is a 5-membered heteroaryl optionally substituted with a carbocycle.

75. A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, each of which is selected from halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～６ 75. The compound or salt of claim 74, optionally substituted with cycloalkyl.

76. A is selected from oxazolyl, isoxazolyl, oxadiazolyl, each of which is halogen, -OR １１Ａ , -N(R １１Ａ ) ２ , -C(O)R １１Ａ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～６ 76. The compound or salt of claim 75, optionally substituted with cycloalkyl.

77. A, 【Chemical 36】 77. The compound or salt of claim 76, selected from:

78. Formula III is represented by formula (IV): 【Chemical 37】 or a pharma- ceutically acceptable salt thereof, wherein: A is a 5- to 6-membered heteroaryl and C ３～６ carbocyclic rings, each of which is selected from Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -C(O)OR １１ , -OC(O)R １１ , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , -CN; and Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN,C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～１０ Alkyl, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =N(R １１ ), and -CN, １～１０ Alkyl; and B is -C(H)(R ５ ) ２ and C ３～１０ carbocyclic rings, each C ３～１０ The carbocyclic ring is ハロゲン、-OR １２ 、-SR １２ 、-N(R １２ ) ２ 、-C(O)R １２ 、-C(O)N(R １２ ) ２ 、-N(R １２ )C(O)R １２ 、-N(R １２ )S(O) ２ R １２ 、-C(O)OR １２ 、-OC(O)R １２ 、-S(O)R １２ 、-S(O) ２ R １２ 、-NO ２ 、=O、=S、=N(R １２ )、-CN; C １～１０ Alkyl and C ３～１０ Carbocyclic rings, each of which is halogen, -OR １２ , -SR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -S(O)R １２ , -S(O) ２ R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN,C ３～１０ and optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle, ３～１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each independently selected from halogen, —OR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -NO ２ , =O, =N(R １２ ), and -CN, １～１０ Alkyl and C ３～１０ Carbocyclic ring; and Each R ５ for each occurrence, (i), (ii), and (iii) of the following: (i)ハロゲン、-OR １３ 、-SR １３ 、-N(R １３ ) ２ 、-C(O)R １３ 、-C(O)N(R １３ ) ２ 、-N(R １３ )C(O)R １３ 、-N(R １３ )S(O) ２ R １３ 、-C(O)OR １３ 、-OC(O)R １３ 、-S(O)R １３ 、-S(O) ２ R １３ 、-NO ２ 、-CN; (ii) halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), C optionally substituted with one or more substituents independently selected from -CN １～１０ Alkyl; and (iii) Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -N(R １３ ) S (O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), —CN; and halogen, —OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ C optionally substituted with one or more substituents independently selected from alkyl, ３～１０ Carbocyclic ring; are independently selected from Each R １ But every time it appears, Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -N(R １４ ) S (O) ２ R １４ , -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), -CN; and Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), and —CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; are independently selected from R ２ but, Hydrogen, halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -N(R １５ ) S (O) ２ R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , -CN; and Halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , =O, =S, =N(R １５ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; is selected from Each R ３ But every time it appears, Hydrogen, halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , -CN; and Halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; or Each R ４ But every time it appears, Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN; and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S (O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN, optionally substituted with one or more substituents independently selected from １～１０ Alkyl; are independently selected from R １１ , R １２ , R １３ , R １４ , R １５ , R １６ , and R １７ But for each occurrence, hydrogen; Halogen, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , =O, -CN, C ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～６ Alkyl, each C ３～１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings are not limited to halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２、 - NO ２ , ═O, and —CN; １～６ Alkyl; and Halogen, —OH, —O—C １～６ Alkyl, —O—C １～６ Haloalkyl, -NH ２ , -NO ２ , ═O, and —CN, optionally substituted with one or more substituents independently selected from ３～１０ Carbocycles and 3- to 10-membered heterocycles; are independently selected from n is selected from 1 and 2; m is selected from 0, 1, and 2; p is selected from 0, 1, 2, 3, 4, 5, and 6; 72. A compound or salt according to claim 71.

79. 79. The compound or salt of claim 78, wherein n is 1.

80. 80. The compound or salt of claim 78 or 79, wherein formula (IV) is represented by the structure of formula (IV-a): 【Chemical Formula 38】

81. 79. The compound or salt of claim 78, wherein n is 2.

82. The compound or salt of claim 78 or 81, wherein formula (IV) is represented by the structure of formula (IV-b): 【Chemical 39】

83. A is a 5-membered heteroaryl; Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -CN; and Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -C.N., C. ３～１０ C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle １～６ Alkyl, ３～１０ The carbocycle and the 3- to 10-membered heterocycle are each -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ and -CN, １～６ Alkyl; 83. The compound or salt of any one of claims 78 to 82, which is a 5-membered heteroaryl optionally substituted with one or more substituents independently selected from:

84. A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any one of which is halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ and one or more C optionally substituted with one or more substituents independently selected from -CN. １～６ 84. The compound or salt of claim 83, optionally substituted with alkyl.

85. A is halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -NO ２ and -CN, optionally substituted with one or more substituents independently selected from １～６ 85. The compound or salt of claim 84, which is pyrazolyl optionally substituted with alkyl.

86. 86. The compound or salt of claim 85, wherein A is pyrazolyl optionally substituted with methyl, ethyl, isopropyl, and propyl.

87. A, 【Chemistry 40】 87. The compound or salt of claim 86,

88. A is selected from pyrazolyl, oxazolyl, isoxazolyl, and oxadiazolyl, any of which is selected from halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ and one or more C optionally substituted with one or more substituents independently selected from -CN. １～６ 84. The compound or salt of claim 83, optionally substituted with alkyl.

89. A is selected from pyrazolyl, oxazolyl, and isoxazolyl, each of which is selected from one or more C １～６ Alkyl and C １～６ 89. The compound or salt of claim 88, optionally substituted with haloalkyl.

90. A, 【Chemistry 41】 90. The compound or salt of claim 89, selected from:

91. B is -C(H)(R ５ ) ２ The compound or salt according to any one of claims 78 to 90,

92. -C(H)(R ５ ) ２ Each R ５ but, Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , -CN; Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; and Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN,C １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～１０ Carbocyclic ring; 92. The compound or salt of claim 91, independently selected from:

93. -C(H)(R ５ ) ２ Each R ５ is halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN,C １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～６ 93. The compound or salt of claim 92, independently selected from carbocycles.

94. -CH(R ５ ) ２ but, 【Chemistry 42】 94. The compound or salt of claim 93,

95. -C(H)(R ５ ) ２ Each R ５ but, Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; and Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN,C １～６ Alkyl, and C １～６ C optionally substituted with one or more substituents independently selected from haloalkyl ３～１０ Carbocyclic ring; 93. The compound or salt of claim 92, independently selected from:

96. -C(H)(R ５ ) ２ Each R ５ But, C １～６ Alkyl, C １～６ Haloalkyl, C ３～７ cycloalkyl, and phenyl; ３～７ Cycloalkyl and phenyl are each independently halogen, C １～６ Alkyl, and C １～６ 96. The compound or salt of claim 95, optionally substituted with one or more substituents independently selected from haloalkyl.

97. -CH(R ５ ) ２ but, 【Chemistry 43】 97. The compound or salt of claim 96, selected from:

98. B is C ６～１０ A carbocyclic ring, Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN, and Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; C optionally substituted with one or more substituents independently selected from ６～１０ 91. The compound or salt of any one of claims 78 to 90, which is carbocyclic.

99. B is selected from cyclohexyl and cycloheptyl, both of which are Halogen, -OR １２ , N(R １２ ) ２ , -NO ２ , -CN; and Halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), and —CN, optionally substituted with one or more substituents independently selected from １～６ Alkyl; 99. The compound or salt of claim 98, optionally substituted with one or more substituents independently selected from:

100. B, 【Chemistry 44】 100. The compound or salt of claim 99,

101. B, 【Chemistry 45】 100. The compound or salt of claim 99, selected from:

102. 102. The compound or salt according to any one of claims 78 to 101, wherein m is 0.

103. Each R ３ Each occurrence represents hydrogen, halogen, -OR １６ , -N(R １６ ) ２ , -NO ２ , -C.N., C. １～３ Alkyl, and C １～３ 103. The compound or salt of any one of claims 78 to 102, independently selected from haloalkyl.

104. Each R ３ 104. The compound or salt of claim 103, wherein is hydrogen.

105. R ２ The compound or salt according to any one of claims 78 to 104, wherein is hydrogen.

106. 106. The compound or salt of any one of claims 78 to 105, wherein p is selected from 0, 1, 2, 3, and 4.

107. Each R １ Each occurrence represents hydrogen, halogen, -OR １４ , -N(R １４ ) ２ , -NO ２ , -C.N., C. １～６ Alkyl, and C １～６ 107. The compound or salt of any one of claims 78 to 106, independently selected from haloalkyl.

108. Each R １ Each occurrence of halogen and -CF ３ 108. The compound or salt of claim 107, independently selected from:

109. Formula (III) 【Chemistry 46】 【Chemistry 47】 or a pharma- ceutically acceptable salt thereof.

110. A pharmaceutical composition comprising a compound or salt according to any one of claims 1 to 109 and a pharma- ceutically acceptable excipient.

111. 110. A method of modulating IL-17A in a subject in need thereof, comprising administering to said subject a compound or salt according to any one of claims 1 to 109, or a pharmaceutical composition according to claim 110.

112. 110. A method of treating an inflammatory disease or condition, comprising administering to a subject in need of treatment for an inflammatory disease or condition a compound or salt according to any one of claims 1 to 109, or a pharmaceutical composition according to claim 110.

113. 113. The method of claim 112, wherein the inflammatory disease or condition is selected from psoriasis vulgaris, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis.

Images