Replaced 6-Imidazopyridazine IL-17A Modulators and Their Uses

Description

"SUBSTITUTED 6-IMIDAZOPYRIDAZINE IL-17A MODULATORS AND THEIR USES" BACKGROUND OF THE INVENTION

[001] The IL-17 family consists of six cytokines (IL-17A to IL-17F). Interleukin-17A (IL-17A) is an established pro-inflammatory cytokine 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 signaling. IL-17A is an important pathological cytokine expressed by Th17 cells, which are involved in the pathology of inflammation and autoimmunity, and also by CD8+ T cells, γδ cells, NK cells, NKT cells, macrophages, and dendritic cells. Furthermore, IL-17A and Th17 are necessary for defense against various microbes, despite their involvement in inflammation and autoimmune diseases. Additionally, IL-17A can act in cooperation with other inflammatory cytokines, such as TNF-α, IFN-γ, and IL-1β, to mediate pro-inflammatory effects.

[002] To date, there are a few approved biological drugs (Secukinumab and Ixekizumab) to modulate IL-17A in the treatment of inflammatory diseases such as psoriasis, ankylosing spondylitis, and psoriatic arthritis. These treatments require injection into the patient, as they are not readily absorbed by the intestine when ingested orally. In addition, these approved biological treatments have a high entry cost for patients, limiting their availability to the patient population in need of them.

[003] There are some small molecule IL-17A modulators approved for oral administration. However, although they offer the convenience of oral administration and a lower entry cost for patients, Petition 870250091144, dated 06 / 10 / 2025, page 10 / 263 2 / 184 do not have the efficacy of approved biological products. Therefore, there is a need for the development of potent small molecule IL-17A modulators for the treatment of inflammatory diseases and other associated disorders. SUMMARY OF THE INVENTION

[004] In certain respects, the present provides a compound represented by the structure of Formula (A): CDλι R3T J / )—(O R34rXiM'N\ HN^ °<^X R4A HN^^n (R1)P(A), Or a pharmaceutically acceptable salt thereof, where: X is selected from N or CR2; A is selected from (a) and (b): (a) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11A, -SR11A, -N(R11A)2, C(O)R11A, -C(O)N(R11A)2, -N(R11A)C(O)R11A-C(O)OR11A, -OC(O)R11A, S(O)R11A, -S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN; (b) -(CR'R")m(3- to 10-membered heterocycle), -(CR'R'')m(C3-10 carbocycle), -O(CR'R'')m(3- to 10-membered heterocycle), and -O-(CR'R'')m(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents selected independently from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11,-C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11,-NO2, -CN; C1-10 alkyl optionally substituted with one or more Petition 870250091144, dated 06 / 10 / 2025, p. 11 / 263 3 / 184 independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), -CN, and C1-10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11A, -SR11A, -N(R11A)2, -C(O)R11A, C(O)N(R11A)2, -N(R11A)C(O)R11A, -C(O)OR11A, -OC(O)R11A, -S(O)R11A, S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and C1-10 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; each R' is selected from hydrogen, halogen, -OR18, -N(R18)2, -C(O)R18, C(O)N(R18)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more of halogens, -OR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -NO2, and -CN; each R'' is selected from hydrogen, halogen, -OR19, -N(R19)2, -C(O)R19, C(O)N(R19)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more of halogens, -OR19, -N(R19)2, -C(O)R19, -C(O)N(R19)2, -NO2, and -CN; B is selected from -C(R5)3 and C3-10 carbocycle, where the C3-10 carbocycle is optionally replaced with one or more substituents independently selected from: Petition 870250091144, dated 06 / 10 / 2025, p. 12 / 263 4 / 184 halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2R12, -C(O)OR12, -OC(O)R12, S(O)R12, -S(O)2R12,-NO2, =O, =S, =N(R12), -CN; C1-10 alkyl and C3-10 carbocycle, any of which is optionally substituted with one or more independently selected halogen substituents, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -NO2, =O, =N(R12), and -CN; each R5 is independently selected in each occurrence of (i), (ii), and (iii): (i) hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​- C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​S(O)R13, ​​-S(O)2R13, -NO2, -CN; (ii) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), -CN; and (iii) C3-10 carbocycle optionally substituted with one or more independently selected substituents: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, NO2, =O, =S, =N(R13), -CN; and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, Petition 870250091144, dated 06 / 10 / 2025, page 13 / 263 5 / 184 C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13,S(O)2R13, -NO2, =O, =S, =N(R13), and -CN; Each R1 is independently selected in each occurrence of: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14,C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2R14, -C(O)OR14, -OC(O)R14,S(O)R14, -S(O)2R14,-NO2, =O, =S, =N(R14), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR14A, -SR14A, -N(R14A)2, -C(O)R14A, -C(O)N(R14A)2, -N(R14A)C(O)R14A, -C(O)OR14A, OC(O)R14A, -S(O)R14A, -S(O)2R14A, -NO2, =O, =S, =N(R14A), and -CN; or two R1 substituents can link to form a C3-6 carbocycle or 3- to 6-membered carbocycle, wherein the C3-6 carbocycle and 3- to 6-membered carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1. 10 alkyl and C3-10 carbocycle, the C1-10 alkyl and C3-10 carbocycle are each independently substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN; R2 is selected from: hydrogen, halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -N(R15)S(O)2R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, -CN; Petition 870250091144, dated 06 / 10 / 2025, p. 14 / 263 6 / 184 C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR15, -SR15, -N(R15)2, -C(O)R15, C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, =O, =S, =N(R15), and -CN; R2 and R1 can link to form a 3- to 6-membered carbocycle, wherein the 3- to 6-membered carbocycle is optionally replaced with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R10)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), and -CN; Each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, N(R16)S(O)2R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR16, -SR16, -N(R16)2, -C(O)R16, C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, NO2, =O, =S, =N(R16), and -CN; L is selected from a linkage, -O-, and C1-6 alkylene optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, CN; Ring D is selected from C3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; Petition 870250091144, dated 06 / 10 / 2025, p. 15 / 263 7 / 184 Optionally substituted C1-10 alkyl with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; R11, R11A, R12, R13, R14, R14A, R15, R16, R17, R18, R19, R20, and R21 are each independently selected in each occurrence of: hydrogen; C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; m is selected from 0, 1, and 2; z is selected from 1 and 2; Petition 870250091144, dated 06 / 10 / 2025, p. 16 / 263 8 / 184 n is selected from 1, 2, and 3; ep is selected from 0, 1, 2, 3, 4, 5, and 6.

[005] In certain modalities, Formula (A) or (I) is represented by the structure of Formula (Ia): ( D ) Χ-Χχχ^N B R3J J? z>—( OR3y^N^NX hn^ °yX2 a HN^\ (r1)p (Ia).

[006] In certain modalities, formula (A) or (I) is represented by the structure of Formula (Ib): ( D ) Χ^χχ B R3T J p r3V^N'n^ hn^ °xJ^R2A HN^J (r1)p (Ib).

[007] In certain respects, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound or salt of Formula (A), (I), (Ia), or (Ib).

[008] In certain respects, the present invention provides a method of modulating IL-17A in an individual in need thereof, comprising administering to the individual a compound or salt of Formula (A), (I), (Ia), or (Ib), or a pharmaceutical composition thereof.

[009] In certain aspects, the present invention provides a method of treating an inflammatory condition or disease comprising administering to the individual a compound or salt of Formula (A), (I), (Ia), or (Ib), or a pharmaceutical composition thereof. In some embodiments, the inflammatory condition or disease is selected from platelet psoriasis, guttate psoriasis, Petition 870250091144, dated 06 / 10 / 2025, page 17 / 263 9 / 184 inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis and non-infectious uveitis. Incorporation by Reference

[0010] All publications, patents and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference. DETAILED DESCRIPTION OF THE INVENTION

[0011] Although preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided only by way of example. Numerous variations, alterations, and substitutions will now 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 employed in the practice of the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents are covered by them. DEFINITIONS

[0012] Unless otherwise defined, all technical and scientific terms used herein have the same meaning commonly understood by one skilled in the art to which this invention pertains. All patents and publications mentioned herein are incorporated by reference.

[0013] As used in the specification and claims, the singular form “a, an”, “an”, and “the” includes plural references, unless the context clearly indicates otherwise.

[0014] Alkyl refers to a monovalent radical in a hydrocarbon chain. Petition 870250091144, dated 06 / 10 / 2025, p. 18 / 263 10 / 184 non-linear or branched, consisting solely of carbon and hydrogen atoms, without unsaturation and preferably with one to twelve carbon atoms (i.e., C1-C12 alkyl). The alkyl is linked to the rest of the molecule through a single bond. In certain embodiments, an alkyl comprises from one to twelve carbon atoms (i.e., C1-C12 alkyl). In certain embodiments, an alkyl comprises from one to eight carbon atoms (i.e., C1-C8 alkyl). In other embodiments, an alkyl comprises from one to five carbon atoms (i.e., C1-C5 alkyl). In other embodiments, an alkyl comprises from one to four carbon atoms (i.e., C1-C4 alkyl). In other embodiments, an alkyl comprises from one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, an alkyl group comprises one to two carbon atoms (i.e., C1-C2 alkyl). In other embodiments, an alkyl group comprises one carbon atom (i.e., C1 alkyl).In other embodiments, an alkyl group comprises from five to fifteen carbon atoms (i.e., C5-C15 alkyl). In other embodiments, an alkyl group comprises from five to eight carbon atoms (i.e., C5-C8 alkyl). In other embodiments, an alkyl group comprises from two to five carbon atoms (i.e., C2-C5 alkyl). In other embodiments, an alkyl group comprises from three to five carbon atoms (i.e., C3-C5 alkyl). For example, the alkyl group may be linked to the rest of the molecule by a single bond, such as methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl), and the like.

[0015] Alkenyl refers to a linear or branched hydrocarbon chain radical consisting exclusively of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12 alkenyl). In certain embodiments, an alkenyl comprises from two to eight carbon atoms. Petition 870250091144, dated 06 / 10 / 2025, p. 19 / 263 11 / 184 bono (i.e., C2-C8 alkenyl). In certain embodiments, an alkenyl group comprises from two to six carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, an alkenyl group comprises from two to four carbon atoms (i.e., C2-C4 alkenyl). The alkenyl group is linked 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.

[0016] Alkynyl refers to a linear or branched hydrocarbon chain radical consisting exclusively of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12 alkynyl). In certain embodiments, an alkynyl comprises from two to eight carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, an alkynyl comprises from two to six carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, an alkynyl comprises from two to four carbon atoms (i.e., C2-C4 alkynyl). The alkynyl is linked to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0017] Alkylene refers to a linear divalent hydrocarbon chain that links the rest of the molecule to a radical group, consisting only of carbon and hydrogen, containing no unsaturation and preferably having from one to twelve carbon atoms. For example, methylene, ethylene, propylene, butylene and the like. The alkylene chain is linked to the rest of the molecule by a single bond and to the radical group by 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 optionally be substituted by one or more substituents, such as the substituents described herein. In certain embodiments, an alkylene comprises from one to ten carbon atoms (i.e., C1-C10 alkylene). In certain embodiments, an alkylene comprises from one to eight carbon atoms (i.e., C1-C8 alkylene). Petition 870250091144, dated 06 / 10 / 2025, p. 20 / 263 12 / 184 In other embodiments, an alkylene comprises from one to five carbon atoms (i.e., C1-C5 alkylene). In other embodiments, an alkylene comprises from one to four carbon atoms (i.e., C1-C4 alkylene). In other embodiments, an alkylene comprises from one to three carbon atoms (i.e., C1-C3 alkylene). In other embodiments, an alkylene comprises from one to two carbon atoms (i.e., C1-C2 alkylene). In other embodiments, an alkylene comprises one carbon atom (i.e., C1 alkylene). In other embodiments, an alkylene comprises from five to eight carbon atoms (i.e., C5-C8 alkylene). In other embodiments, an alkylene comprises from two to five carbon atoms (i.e., C2-C5 alkylene). In other embodiments, an alkylene comprises from three to five carbon atoms (i.e., C3-C5 alkylene).

[0018] Alkenylene refers to a linear bivalent hydrocarbon chain that links the rest of the molecule to a radical group, consisting exclusively of carbon and hydrogen, containing at least one carbon-carbon double bond and preferably having from two to twelve carbon atoms. The alkenylene chain is linked to the rest of the molecule by a single bond and to the radical group by 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 optionally be substituted by one or more substituents, such as the substituents described herein. In certain embodiments, an alkenylene comprises from two to ten carbon atoms (i.e., C2-C10 alkenylene). In certain embodiments, an alkenylene comprises from two to eight carbon atoms (i.e., C2-C8 alkenylene).In other embodiments, an alkenylene comprises from two to five carbon atoms (i.e., C2-C5 alkenylene). In other embodiments, an alkenylene comprises from two to four carbon atoms (i.e., C2-C4 alkenylene). In other embodiments, an alkenylene comprises from two to... Petition 870250091144, dated 06 / 10 / 2025, p. 21 / 263 13 / 184 three carbon atoms (i.e., C2-C3 alkenylene). In other embodiments, an alkenylene comprises two carbon atoms (i.e., C2 alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (i.e., C5-C8 alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (i.e., C3-C5 alkenylene).

[0019] Alkynylene refers to a linear bivalent hydrocarbon chain that links the rest of the molecule to a radical group, consisting only of carbon and hydrogen, containing at least one carbon-carbon triple bond and preferably having from two to twelve carbon atoms. The alkynylene chain is linked to the rest of the molecule by a single bond and to the radical group by 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 may optionally be substituted by one or more substituents, such as the substituents described herein. In certain embodiments, an alkynylene comprises from two to ten carbon atoms (i.e., C2-C10 alkynylene). In certain embodiments, an alkynylene comprises from two to eight carbon atoms (i.e., C2-C8 alkynylene).In other embodiments, an alkynylene comprises from two to five carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, an alkynylene comprises from two to four carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, an alkynylene comprises from two to three carbon atoms (i.e., C2-C3 alkynylene). In other embodiments, an alkynylene comprises from two carbon atoms (i.e., C2 alkynylene). In other embodiments, an alkynylene comprises from five to eight carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, an alkynylene comprises from three to five carbon atoms (i.e., C3-C5 alkynylene).

[0020] The term “Cx-y” when used in conjunction with a chemical portion Petition 870250091144, dated 06 / 10 / 2025, p. 22 / 263 14 / 184 mica, such as alkyl, alkenyl, or alkynyl, is intended to include groups containing doxay carbons in the chain. For example, the term “C1-6 alkyl” refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl groups and branched-chain alkyl groups containing from 1 to 6 carbons. The term -Cx-y alkylene- refers to a substituted or unsubstituted alkylene chain with doxay carbons in the alkylene chain. For example, -C1-6 alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any of which is optionally substituted.

[0021] The terms “Cx-y alkenyl” and “Cx-y alkynyl” refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyl groups described above, but containing at least one double or triple bond, respectively. The term -Cx-y alkenylene- refers to an alkylene chain substituted or unsubstituted with xay carbons in the alkenylene chain. For example, -C2-6 alkenylene- can be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any of which is optionally substituted. An alkenylene chain may have one or more double bonds in the alkenylene chain. The term -Cxy alkynylene- refers to an alkynylene chain substituted or unsubstituted with xay carbons in the alkynylene chain. For example, -C2. 6. Alkynylene can be selected from ethinylene, propylene, butylene, pentylene, and hexylene, any of which can be optionally substituted.An alkynylene chain can have one or more triple bonds in the alkynylene chain.

[0022] The term carbocycle, as used herein, refers to a saturated, unsaturated, or aromatic ring in which every ring atom is carbon. Carbocycles include monocyclic rings with 3 to 12 members and bicyclic rings with 6 to 12 members. Each ring of a bicyclic carbocycle can be selected from Petition 870250091144, dated 06 / 10 / 2025, p. 23 / 263 15 / 184 saturated, unsaturated, and aromatic rings. Bicyclic carbocycles can be fused, bridged, or spirocyclic ring systems. In some embodiments, the bicyclic carbocycle is selected from among fused carbocycles, bridged carbocycles, and spirocyclic carbocycles. In some embodiments, the carbocycle is an aryl. In some embodiments, the carbocycle is a cycloalkyl. In some embodiments, the carbocycle is a cycloalkenyl. In an exemplary embodiment, an aromatic ring, for example, phenyl, can be fused to a saturated or unsaturated ring, for example, cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings, as the valence permits, is included in the definition of carbocyclic. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The carbocycle may optionally be replaced by one or more substituents, such as the substituents described herein.

[0023] Cycloalkyl refers to a stable, fully saturated monocyclic or polycyclic hydrocarbon radical consisting exclusively of carbon and hydrogen atoms, including fused or bridging ring systems, and preferably having from three to twelve carbon atoms (i.e., C3-12 cycloalkyl). In certain embodiments, a cycloalkyl comprises from three to ten carbon atoms (i.e., C3-10 cycloalkyl). In other embodiments, a cycloalkyl comprises from five to seven carbon atoms (i.e., C5-7 cycloalkyl). The cycloalkyl may be linked to the rest 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]heptaniyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanil, and the like. Cycloalkyl may be optionally substituted with one or more substituents, such as those substituents described herein. Petition 870250091144, dated 06 / 10 / 2025, p. 24 / 263 16 / 184

[0024] Cycloalkenyl refers to a stable unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting exclusively of carbon and hydrogen atoms, including fused or bridging ring systems, preferably having from three to twelve carbon atoms and comprising at least one double bond (i.e., C3-12 cycloalkenyl). In certain embodiments, a cycloalkenyl comprises from three to ten carbon atoms (i.e., C3-10 cycloalkenyl). In other embodiments, a cycloalkenyl comprises from five to seven carbon atoms (i.e., C5-7 cycloalkenyl). The cycloalkenyl may be linked to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Cycloalkenyl can optionally be replaced by one or more substituents, such as those described herein.

[0025] Aryl refers to a radical derived from a monocyclic or multicyclic aromatic hydrocarbon ring system by removing a hydrogen atom from a carbon atom in the ring. The monocyclic or multicyclic aromatic hydrocarbon ring system contains only hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, that is, it contains a delocalized cyclic (4n+2) π-electron system, according to Hückel's theory. The ring system from which aryl groups are derived includes, but is not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. Aryl can be optionally substituted by one or more substituents, such as the substituents described herein.

[0026] A “Cx-y carbocycle” is intended to include groups containing x and y carbons in a ring. For example, the term “C3-6 carbocycle” may be a saturated or unsaturated aromatic ring system containing 3 to 6 carbon atoms — any of which is optionally substituted as per Petition 870250091144, dated 06 / 10 / 2025, page 25 / 263 17 / 184 needed here.

[0027] The term heterocycle, as used herein, refers to a saturated, unsaturated, non-aromatic, or aromatic ring comprising one or more heteroatoms. Exemplary heteroatoms include atoms of N, O, Si, P, B, and S. Heterocycles include monocyclic rings of 3 to 10 members and bicyclic rings of 6 to 12 members. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof.In some embodiments, the heterocycle comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocycle may be linked to the remainder of the molecule through any atom of the heterocycle, if the valence permits, such as a carbon or nitrogen atom of the heterocycle. In some embodiments, the 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 may optionally be substituted by one or more substituents, such as the substituents described herein. Bicyclic heterocycles may be a fused heterocycle, a bridging heterocycle, or a spirocyclic heterocycle.In one exemplary embodiment, a heterocycle, for example, pyridyl, can be fused to a saturated or unsaturated ring, for example, cyclohexane, cyclopentane, or cyclohexene. In some embodiments, the bicyclic heterocycle is a heterocy. Petition 870250091144, dated 06 / 10 / 2025, p. 26 / 263 18 / 184 clo bridging (e.g., 6-oxa-3-azabicyclo[3.1.1]heptanil). In some embodiments, the bicyclic heterocycle is a spirocyclic heterocycle (e.g., 2-oxa-6-azaespiro[3.3]heptanil or 4-oxa-7-azaespiro[2.5]octanyl). The heterocycle may optionally be replaced by one or more substituents, such as the substituents described herein.

[0028] Heterocycloalkyl refers to a stable 3- to 12-membered non-aromatic ring radical comprising two to twelve carbon atoms and at least one heteroatom, wherein each heteroatom may be selected from N, O, Si, P, B, and S atoms. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. The heterocycloalkyl may be selected from monocyclic or bicyclic ring systems, fused or bridged. The heteroatoms in the heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized.The heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl is linked to the rest of the molecule through any atom of the heterocycloalkyl, as long as the valence allows, such as any carbon or nitrogen atoms of the heterocycloalkyl. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithyanyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tritianyl, tetrahydropyranyl, thiomorpholini. Petition 870250091144, dated 06 / 10 / 2025, page 27 / 263 19 / 184 la, thiamorpholinyl, 1-oxothiomorpholinyl and 1,1-dioxothiomorpholinyl. The heterocycloalkyl group may be optionally replaced by one or more substituents, such as the substituents described herein.

[0029] The term heteroaryl refers to a radical derived from a 5- to 12-membered aromatic ring radical comprising at least one heteroatom, preferably between one and four heteroatoms. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof.As used herein, the heteroaryl ring may be selected from fused or bridged monocyclic or bicyclic ring systems, wherein at least one of the rings in the ring system is aromatic, i.e., contains a delocalized cyclic (4n+2) electron system according to Hückel theory. The heteroatom(s) in the heteroaryl radical may optionally be oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl may be linked to the rest of the molecule via any atom of the heteroaryl, if valence permits, such as a carbon or nitrogen atom of the heteroaryl. Heteroaryl includes aromatic single-ring structures, preferably 5- to 6-membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms.Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like. A heteroaryl group can be... Petition 870250091144, dated 06 / 10 / 2025, p. 28 / 263 20 / 184 optionally substituted by one or more substituents, such as the substituents described herein. Heteroaryl also includes polycyclic ring systems with 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, for example, the other rings may be aromatic or non-aromatic carbocyclic, or heterocyclic. The heteroaryl may be optionally substituted by one or more substituents, such as the substituents described herein.

[0030] An X-membered heterocycle refers to the number of endocyclic atoms, i.e., X, in the ring. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 endocyclic atoms, such as triazole, oxazole, thiophene, etc.

[0031] Alkoxy refers to a radical linked through an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above.

[0032] Halo or halogen refers to halogen substituents, such as bromine, chlorine, fluorine, and iodine substituents.

[0033] As used herein, the term haloalkyl or haloalkane refers to an alkyl radical, as defined above, which is substituted by one or more halogen radicals, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally substituted. Examples of halogen-substituted alkanes (“haloalkanes”) include halomethane (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di- and trihalomethane (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 combinations of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F). Petition 870250091144, dated 06 / 10 / 2025, page 29 / 263 21 / 184 and I). When an alkyl group is replaced by more than one halogen radical, each halogen can be selected independently, for example, 1-chloro,2-fluoroethane.

[0034] The term substituted refers to moieties that have substituents that replace a hydrogen atom on one or more carbons or replaceable heteroatoms, for example, an NH or NH2 of a compound. It is understood that substitution or substituted by includes the implicit condition that such substitution conforms to the permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound that does not undergo spontaneous transformation, such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties that have substituents that replace two hydrogen atoms on the same carbon atom, such as the substitution of the two hydrogen atoms on a single carbon by an oxo, imino, or thioxo group. As used herein, the term substituted is considered to include all permitted substituents of organic compounds.In a broad sense, permitted substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. Permitted substituents may be one or more, the same or different for appropriate organic compounds. Preferably, optionally substituted by one or more substituents means substituted once or twice. Preferably, optionally substituted by one or more substituents means substituted once.

[0035] In some embodiments, the substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=NNH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, Petition 870250091144, dated 06 / 10 / 2025, p. 30 / 263 22 / 184 -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa (where t is 1 or 2), -Rb-S(O)tRa (where t is 1 or 2), -Rb-S(O)tORa (where t is 1 or 2), and -Rb-S(O)tN(Ra)2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralquinyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may optionally be substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=NNH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2);wherein each Ra is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, the valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=NNH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2);and wherein each Rbé independently selected from a direct linkage or a linear or branched chain of alkylene, alkenylene, or alkynylene, and each Rcé a linear or branched chain of alkylene, alkenylene, or alkynylene. It shall be understood by those skilled in the art that substituents may, of themselves, be substituted, if appropriate.

[0036] The term salt or pharmaceutically acceptable salt refers to salts Petition 870250091144, dated 06 / 10 / 2025, page 31 / 263 23 / 184 derivatives of a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0037] The term “pharmaceutically acceptable” is used here to refer to those compounds, materials, compositions, and / or pharmaceutical forms that are, within the scope of good medical sense, suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic response or other problem or complication, consistent with a reasonable benefit / risk ratio.

[0038] The expression “pharmaceutically acceptable excipient” or “pharmaceutically acceptable vehicle,” as used herein, means a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each vehicle must be acceptable in the sense that it is compatible with the other ingredients in the formulation and does not cause harm to the patient.

[0039] 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, canines, equines, felines, swine, bovines, ungulates, lagomorphs, and the like). In various modalities, the subject may be a human (e.g., adult male, adult female, adolescent male, adolescent female, male child, female child) under the care of a physician or other health professional in a hospital, as an outpatient, or in another clinical setting. In certain modalities, the individual may not be under the care or prescription of a physician or other health professional.

[0040] As used here, the phrase an individual in need of the same Petition 870250091144, dated 06 / 10 / 2025, page 32 / 263 24 / 184 mo refers to an individual, as described below, who suffers from, or is at risk of, a condition to be treated prophylactically or therapeutically with a compound or salt described herein.

[0041] The terms “administer”, “administered”, “administers” and “administering” are defined as the delivery of a composition to an individual via a route known in the art, including, but not limited to, intravenous, intra-arterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal or intraperitoneal routes of administration. In certain embodiments, oral routes of administration of a composition may be used. The terms “administration”, “administered”, “administers” and “administering” a compound should be understood as the delivery of a compound of the invention or a prodrug of a compound of the invention to the individual in need thereof.

[0042] As used herein, treatment or treating refers to an approach to obtain beneficial or desired results in relation to a disease, disorder, or medical condition, including, but not limited to, a therapeutic benefit and / or a prophylactic benefit. In certain modalities, treatment or treatment involves the administration of a compound or composition described herein to an individual. A therapeutic benefit may include the eradication or improvement of the underlying disorder being treated. Furthermore, a therapeutic benefit may be achieved by the eradication or improvement of one or more physiological symptoms associated with the underlying disorder, such as the observation of an improvement in the individual, even though the individual may still be affected by the underlying disorder.In certain modalities, for prophylactic benefit, the compositions are administered to an individual at risk of developing a specific disease or to an individual who reports one or more physiological symptoms of a disease, even if a diagnosis of that disease has not yet been made. The term treatment may include, for example, reducing, delaying, or... Petition 870250091144, dated 06 / 10 / 2025, p. 33 / 263 25 / 184 to alleviate the severity of one or more symptoms of a disease or condition, or may include reducing the frequency with which the symptoms of a disease, defect, disorder or adverse condition, and the like, are experienced by a patient. The term treatment may be used here to refer to a method that results in some level of treatment or improvement of the disease or condition, and may encompass a range of outcomes directed toward that end, including, but not limited to, complete prevention of the condition.

[0043] 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 the treated sample relative to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample.

[0044] A “therapeutic effect”, as the term is used herein, encompasses a therapeutic benefit and / or a prophylactic benefit, as described above. A prophylactic effect includes delaying or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, delaying, halting or reversing the progression of a disease or condition, or any combination thereof. COMPOUNDS

[0045] In some respects, the present invention provides a compound represented by the structure of Formula (A): (R1)P(A), or a pharmaceutically acceptable salt thereof, where: Petition 870250091144, dated 06 / 10 / 2025, p. 34 / 263 26 / 184 X is selected from N or CR2; A is selected from (a) and (b): (a) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11A, -SR11A, -N(R11A)2, - C(O)R11A, -C(O)N(R11A)2, -N(R11A)C(O)R11A-C(O)OR11A, -OC(O)R11A, S(O)R11A, -S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN; (b) -(CR'R")m(3- to 10-membered heterocycle), -(CR'R'')m(C3-10 carbocycle), -O(CR'R")m(3- to 10-membered heterocycle), and -O-(CR'R'')m(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents selected independently from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), -CN, and C1. 10 optionally substituted alkyl groups with one or more independently selected halogen substituents, -OR11A, -SR11A, -N(R11A)2, -C(O)R11A, C(O)N(R11A)2, -N(R11A)C(O)R11A, -C(O)OR11A, -OC(O)R11A, -S(O)R11A, S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independent substituents. Petition 870250091144, dated 06 / 10 / 2025, p. 35 / 263 27 / 184 halogens optionally selected, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and C1-10 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; each R' is selected from hydrogen, halogen, -OR18, -N(R18)2, -C(O)R18, C(O)N(R18)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more of halogens, -OR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -NO2, and -CN; each R'' is selected from hydrogen, halogen, -OR19, -N(R19)2, -C(O)R19, C(O)N(R19)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more of halogens, -OR19, -N(R19)2, -C(O)R19, -C(O)N(R19)2, -NO2, and -CN; B is selected from -C(R5)3 and C3-10 carbocycle, where the C3-10 carbocycle is optionally replaced with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2R12, -C(O)OR12, -OC(O)R12, S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN; C1-10 alkyl and C3-10 carbocycle, any of which is optionally substituted with one or more independently selected halogen substituents, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -NO2, =O, =N(R12), and -CN; each R5 is independently selected in each occurrence of (i), (ii), and Petition 870250091144, dated 06 / 10 / 2025, page 36 / 263 28 / 184 (iii): (i) hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​- C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​S(O)R13, ​​-S(O)2R13, -NO2, -CN; (ii) C3-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), -CN; and (iii) C3-10 carbocycle optionally substituted with one or more independently selected substituents: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, NO2, =O, =S, =N(R13), -CN; and Optionally substituted ci-io alkyl with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​S(O)2R13, -NO2, =O, =S, =N(R13), and -CN; Each R1 is independently selected in each occurrence of: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2R14, -C(O)OR14, -OC(O)R14, S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR14A, Petition 870250091144, dated 06 / 10 / 2025, page 37 / 263 29 / 184 -SR14A, -N(R14A)2, -C(O)R14A, -C(O)N(R14A)2, -N(R14A)C(O)R14A, -C(O)OR14A, OC(O)R14A, -S(O)R14A, -S(O)2R14A, -NO2, =O, =S, =N(R14A), and -CN; or two R1 substituents can link to form a C3-6 carbocycle or 3- to 6-membered carbocycle, wherein the C3-6 carbocycle and 3- to 6-membered carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1. 10 alkyl and C3-10 carbocycle, the C1-10 alkyl and C3-10 carbocycle are each independently substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN; R2 is selected from: hydrogen, halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -N(R15)S(O)2R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR15, -SR15, -N(R15)2, -C(O)R15, C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, =O, =S, =N(R15), and -CN; R2 and R1 can link to form a 3- to 6-membered carbocycle, wherein the 3- to 6-membered carbocycle is optionally replaced with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R10)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), and -CN; Each R3 is selected independently in each hydrogen occurrence. Petition 870250091144, dated 06 / 10 / 2025, p. 38 / 263 30 / 184 halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, N(R16)S(O)2R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR16, -SR16, -N(R16)2, -C(O)R16, C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, NO2, =O, =S, =N(R16), and -CN; L is selected from a linkage, -O-, and C1-6 alkylene optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, CN; Ring D is selected from C3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; Petition 870250091144, dated 06 / 10 / 2025, p. 39 / 263 31 / 184 R11, R11A, R12, R13, R14, R14A, R15, R16, R17, R18, R19, R20, and R21 are each independently selected at each occurrence of: hydrogen; C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; m is selected from 0, 1, and 2; z is selected from 1 and 2; n is selected from 1, 2, and 3; ep is selected from 0, 1, 2, 3, 4, 5, and 6.

[0046] In some embodiments, for the compound or salt of Formula (A), L is selected from a C1-6 alkylene optionally substituted with one or more independently selected substituents of halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, -O, or -CN. In some embodiments, L is C1-6 alkylene optionally substituted with one or more independently selected substituents of halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, -O, or -CN. In some embodiments, L is C1-3 alkylene optionally substituted with one or more independently selected substituents of halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl. In some embodiments, L is selected from methylene, ethylene, and propylene, each of which is optionally substituted with one or more independent substituents. Petition 870250091144, dated 06 / 10 / 2025, p. 40 / 263 32 / 184 independently selected halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl. In some embodiments, L is selected from methylene and ethylene, each of which is optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl. In some embodiments, L is methylene. In some embodiments, L is a connection.

[0047] In some embodiments, for the compound or salt of Formula (A), ring D is a 3- to 10-membered heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle. In some embodiments, ring D is a saturated 4- to 7-membered heterocycle optionally substituted with one or more independently selected halogen, C1-6 alkyl, and C1-6 haloalkyl substituents.

[0048] In some embodiments, for the compound or salt of Formula (A), It is selected from: In some sports, It is selected from: In some sports, It is selected from: faith Petition 870250091144, dated 06 / 10 / 2025, p. 41 / 263 33 / 184

[0049] In some embodiments, for the compound or salt of Formula (A), z is 1.

[0050] In some embodiments, for the compound or salt of Formula (A), z is 2.

[0051] In some modalities, X is N.

[0052] In some modes, X is CR2.

[0053] In some embodiments, for the compound or salt of Formula (A), n is selected from 3. In some embodiments, n is selected from 2. In some embodiments, n is selected from 1.

[0054] In some embodiments, for the compound or salt of Formula (A), A is C1.10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11A, -SR11A, -N(R11A)2, C(O)R11A, -C(O)N(R11A)2, -N(R11A)C(O)R11A, -C(O)OR11A, -OC(O)R11A, S(O)R11A, -S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN. In some embodiments, A is C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11A, -SR11A, -N(R11A)2, C(O)R11A, -C(O)N(R11A)2, -N(R11A)C(O)R11A, -C(O)OR11A, -OC(O)R11A, S(O)R11A, -S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN. In some embodiments, C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11A, -N(R11A)2, -C(O)R11A, NO2, =O, =S, =N(R11A), and -CN. In some embodiments, A is C1-6 alkyl or C16 haloalkyl.

[0055] In some embodiments, for the compound or salt of Formula (A), A is selected from -(CR'R'')m (3- to 10-membered heterocycle), -(CR'R”)m (C3-w carbocycle), -O-(CR'R'')m (3- to 10-membered heterocycle), and -O-(CR'R'')m (C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle being each independently substituted with one or more substituents selected independently from: C1.10 alkyl optionally substituted with one or Petition 870250091144, dated 06 / 10 / 2025, p. 42 / 263 34 / 184 plus independently selected halogen substituents, -OR11, SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), -CN, and C1-10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11A, -SR11A, -N(R11A)2, -C(O)R11A, C(O)N(R11A)2, -N(R11A)C(O)R11A, -C(O)OR11A, -OC(O)R11A, -S(O)R11A, S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN.In some embodiments, A is selected from -(CR'R'')m(3- to 10-membered heterocycle), -(CR'R'')m(C3-10 carbocycle), -O-(CR'R”)m(3- to 10-membered heterocycle), and -O-(CR'R'')m(C3-10 carbocycle), wherein the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents independently selected from the C3-10 carbocycle and the 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and the 3- to 10-membered heterocycle are each optionally substituted with one or more C1-10 alkyl groups optionally substituted with one or more halogen substituents, -OR11A, -SR11A, -N(R11A)2, -C(O)R11A, -C(O)N(R11a)2, -N(R11A)C(O)R11A, C(O)OR11A, -OC(O)R11A, -S(O)R11A, -S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN

[0056] In some embodiments, for compound or salt of Formula (A). B is from -C(R5)3; and each R5 is selected independently in each occurrence of (i), (ii), and (iii): (i) hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​- C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​S(O)R13, ​​-S(O)2R13, -NO2, -CN; (ii) C1-10 alkyl optionally substituted with one or more substituents Petition 870250091144, dated 06 / 10 / 2025, page 43 / 263 35 / 184 independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), -CN; and (iii) C3-10 carbocycle optionally substituted with one or more independently selected substituents of: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, NO2, =O, =S, =N(R13), -CN; and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​S(O)2R13, -NO2, =O, =S, =N(R13), and -CN.

[0057] In some embodiments, for the compound or salt of Formula (A), B is from -C(R5)3; and each R5 is independently selected in each occurrence of (i), and (ii): (i) hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​- C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​S(O)R13, ​​-S(O)2R13, -NO2, -CN; and (ii) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN.

[0058] In some embodiments, for the compound or salt of Formula (A), B is -C(R5)3 and each R5 is independently selected at each occurrence of hydrogen and optionally substituted C1-10 alkyl with one or more independently selected halogen substituents, -OR13, -SR13, N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN. In some Petition 870250091144, dated 06 / 10 / 2025, page 44 / 263 36 / 184 embodiments, B is -C(R5)3 and each R5 is independently selected in each occurrence of hydrogen and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN.

[0059] In some embodiments, for the compound or salt of Formula (A), each R1 is independently selected in each occurrence of C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR14, SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; The C3-10 carbocycle and heterocycle of 3 to 10 members are each optionally substituted with one or more substituents selected from: halogen, -OR14A, -SR14A, -N(R14A)2, -C(O)R14A, -C(O)N(R14A)2, N(R14A)C(O)R14A, -C(O)OR14A, -OC(O)R14A, -S(O)R14A, -S(O)2R14A, -NO2, =O, =S, =N(R14A), and -CN.In some embodiments, each R1 is independently selected in each occurrence of C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected C3-10 carbocycle and 3- to 10-membered heterocycle substituents; the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR14A, -SR14A, -N(R14A)2, -C(O)R14A, -C(O)N(R14A)2, -N(R14A)C(O)R14A, -C(O)OR14A, -OC(O)R14A, -S(O)R14A, -S(O)2R14A, -NO2, =O, =S, =N(R14A), and -CN.

[0060] In some embodiments, for the compound or salt of Formula (A), two R1 substituents may link to form a C3-6 carbocycle or a 3- to 6-membered carbocycle, wherein the C3-6 carbocycle and the 3- to 6-membered carbocycle are each independently substituted with one or more substituents. Petition 870250091144, dated 06 / 10 / 2025, p. 45 / 263 37 / 184 independently selected substituents of: halogen, -OR20, -N(R20)2, C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1-10 alkyl and C3-10 carbocycle, the C1-10 alkyl and C3-10 carbocycle are each independently substituted with one or more independently selected substituents of halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN. In some embodiments, two R1 substituents can link to form a C3-6 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1-10 alkyl and C3-10 carbocycle, where C1-10 alkyl and C3-10 carbocycle are each independently substituted with one or more substituents independently selected from halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN.In some embodiments, two R1 substituents can link to form a C3-6 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1-3 alkyl and C3-6 carbocycle, the C1-3 alkyl and C3-6 carbocycle are each independently substituted with one or more substituents independently selected from halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN.

[0061] In some respects, Formula (A) is represented by the structure of. Formula (I): ( D ) B R3I PARA r3V^n'n'^ / hn^ Mr2 a HN^Çn (R1)P(I), or a pharmaceutically acceptable salt thereof where: A is selected from -(CR'R'')m(heterocycle of 3 to 10 members), -(CR'R'')m(C3-10 Petition 870250091144, dated 06 / 10 / 2025, p. 46 / 263 38 / 184 carbocycle), -O-(CR'R")m(3- to 10-membered heterocycle), and -O-(CR'R'')m(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents selected independently from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; each R' is selected from hydrogen, halogen, -OR18, -N(R18)2, -C(O)R18, C(O)N(R18)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more halogens, -OR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -NO2, -CN; each R'' is selected from hydrogen, halogen, -OR19, -N(R19)2, -C(O)R19, C(O)N(R19)2, -NO2, -CN; and optionally substituted C1-6 alkyl with one or Petition 870250091144, dated 06 / 10 / 2025, p. 47 / 263 39 / 184 more halogen, -OR19, -N(R19)2, -C(O)R19, -C(O)N(R19)2, -NO2, -CN; B is selected from -C(H)(R5)2 and C3-10 carbocycle, where the C3-10 carbocycle is optionally replaced with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2R12, -C(O)OR12, -OC(O)R12, S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN; C1-10 alkyl and C3-10 carbocycle, any of which is optionally substituted with one or more independently selected halogen substituents, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -NO2, =O, =N(R12), and -CN; each R5 is selected independently in each occurrence of (i), (ii), and (iii): (i) halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, - N(R13)C(O)R13, -N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, -CN; (ii) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN; and (iii) C3-10 carbocycle optionally substituted with one or more independently selected substituents: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, Petition 870250091144, dated 06 / 10 / 2025, page 48 / 263 40 / 184 N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), -CN; and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​C(O)N(R13)2, -N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, NO2, =O, =S, =N(R13), and -CN; Each R1 is independently selected in each occurrence of: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2R14, -C(O)OR14, -OC(O)R14, S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), and -CN; or two R1 substituents can link to form a 3- to 6-membered carbocycle, wherein the 3- to 6-membered carbocycle is optionally substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN; R2 is selected from hydrogen, halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, C(O)N(R15)2, -N(R15)C(O)R15, -N(R15)S(O)2R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR15, -SR15, -N(R15)2, - Petition 870250091144, dated 06 / 10 / 2025, p. 49 / 263 41 / 184 C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -S(O)R15, S(O)2R15, -NO2, =O, =S, =N(R15), and -CN; or R2 and R1 can link to form a 3- to 6-membered carbocycle, wherein the 3- to 6-membered carbocycle is optionally replaced with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R10)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), and -CN; Each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, N(R16)S(O)2R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR16, -SR16, -N(R16)2, -C(O)R16, C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, NO2, =O, =S, =N(R16), and -CN; The D ring is selected from C3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents selected independently from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and Petition 870250091144, dated 06 / 10 / 2025, p. 50 / 263 42 / 184 C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, and R21 are each independently selected at each occurrence of: hydrogen; C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; m is selected from 0, 1, and 2; n is selected from 1 and 2; ep is selected from 0, 1, 2, 3, 4, 5, and 6.

[0062] In some embodiments, for the compound or salt of Formula (A) or Formula (I), n is 1.

[0063] In some respects, Formula (A) or Formula (I) is represented Petition 870250091144, dated 06 / 10 / 2025, p. 51 / 263 43 / 184 by the Formula structure (Ia): (la) or a pharmaceutically acceptable salt thereof.

[0064] In some embodiments, for the compound or salt of Formula (Ia), R1, R2, R3, the rings D, A, B and p are each defined as in Formula (A) or Formula (I).

[0065] In some embodiments, for the compound or salt of Formula (A) or Formula (I), n is 2.

[0066] In some respects, Formula (A) or Formula (I) is represented by the structure of Formula (Ib): (Ib) or a pharmaceutically acceptable salt thereof.

[0067] In some embodiments, for the compound or salt of Formula (Ib), R1, R2, R3, the rings D, A, B and p are each defined as in Formula (A) or Formula (I).

[0068] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), 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 Petition 870250091144, dated 06 / 10 / 2025, p. 52 / 263 44 / 184 modalities, p is selected from 3, 4, and 5. In some modalities, p is selected from 4 and 5. In some modalities, p is 0. In some modalities, p is 1. In some modalities, p is 2. In some modalities, p is 3. In some modalities, p is 4. In some modalities, p is 5. In some modalities, p is 6.

[0069] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), m is 1. In some embodiments m is 1 and A is selected from -(CR'R")-(3- to 10-membered heterocycle), -(CR'R'')-(C3-10 carbocycle), -O(CR'R'')-(3- to 10-membered heterocycle), and -O-(CR'R'')-(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and C1-6 alkyl optionally substituted with a Petition 870250091144, dated 06 / 10 / 2025, p. 53 / 263 45 / 184 or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11,-C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0070] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), m is 1 and each of R' and R'' are independently selected from hydrogen, halogen, -OR18, -N(R18)2, -CN, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, m is 1 and each of R' and R'' are independently selected from hydrogen, halogen, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, m is 1 and each of R' and R'' are independently selected from hydrogen and halogen. In some embodiments, m is 1 and each of R' and R'' are independently selected from hydrogen and fluoro.

[0071] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), each of R' and R'' are independently selected from hydrogen, halogen, -OR18, -N(R18)2, -CN, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, R' and R'' are independently selected from hydrogen, halogen, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, R' and R'' are independently selected from hydrogen and halogen. In some embodiments, R' and R'' are independently selected from hydrogen and fluoro.

[0072] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), m is 0. In some embodiments, m is 0 and -(CR'R'') is absent. In some embodiments, m is 0 and A is selected from a 3- to 10-membered heterocycle, C3-10 carbocycle, -O-(3- to 10-membered heterocycle), and -O-(C3-io carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each optionally substituted as described in Formula (A) or (I). In some embodiments, m is 0 and A is selected from a 3- to 10-membered heterocycle, C3-10 carbocycle, -O-(3- to 10-membered heterocycle), and -O-(C3-io carbocycle), the heterocycle Petition 870250091144, dated 06 / 10 / 2025, p. 54 / 263 46 / 184 carbocycles of 3 to 10 members and C3-10 carbocycles are each independently substituted with one or more substituents selected independently from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0073] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), each R1 is selected from halogen, -OR14, -SR14, -N(R14)2, C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2R14, -C(O)OR14, OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN; C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR14, -SR14, Petition 870250091144, dated 06 / 10 / 2025, page 55 / 263 47 / 184 N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, each R1 is selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and C3-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, each R1 is selected from halogen, -OR14, N(R14)2, -C(O)R14, -NO2, -CN, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl.

[0074] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), each R1 is selected from halogen, -OR14, -SR14, -N(R14)2, C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2R14, -C(O)OR14, OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, each R1 is selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, N(R14)S(O)2R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), and -CN.In some embodiments, each R1 is selected from optionally substituted C1-6 alkyl with one or more independently selected halogen substituents, -OR14, -SR14, -N(R14)2, -C(O)R14, C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, NO2, =O, =S, =N(R14), and -CN. In some embodiments, each R1 is selected from halogen, -OR14, -N(R14)2, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, each R1 is selected from halogen and -CF3. In some embodiments, each R1 is -CF3.

[0075] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), two R1 substituents can link to form a carbocation. Petition 870250091144, dated 06 / 10 / 2025, p. 56 / 263 48 / 184 clo of 3 to 6 members, wherein the 3 to 6 membered carbocycle is optionally substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN. In some embodiments, two R1 substituents can link to form a 3- to 6-membered cycloalkyl, wherein the 3- to 6-membered cycloalkyl is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, -NO2, CN; C1-3 alkyl and C3-6 cycloalkyl, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, N(R20)2, -C(O)R20, -NO2, and -CN.In some embodiments, two R1 substituents can link to form a 3-membered cycloalkyl optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, -NO2, -CN; C1-3 alkyl and C3-6 cycloalkyl, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, NO2, and -CN. In some embodiments, two R1 substituents on adjacent carbon atoms can be linked together to form an optionally substituted 3-membered cycloalkyl. In some embodiments, two R1 substituents on adjacent carbon atoms can be linked together to form an optionally substituted 3-membered cycloalkyl, including the two carbon atoms to which the two R1 substituents are linked. of. For example, (r1)p can be represented by, but not limited to, Petition 870250091144, dated 06 / 10 / 2025, p. 57 / 263 49 / 184 or , and may be optionally substituted as described herein. In some embodiments, two R1 substituents may link to form a 4-membered cycloalkyl optionally substituted with one or more independently selected halogen substituents, -OR20, N(R20)2, -C(O)R20, -NO2, and -CN; C1-3 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, -NO2, and -CN. In some embodiments, two R1 substituents on different carbon atoms may link together to form an optionally substituted 4-membered cycloalkyl. In some embodiments, two R1 substituents on different carbon atoms can be linked together to form an optionally substituted 4-membered cycloalkyl group, including the two carbon atoms to which the two R1 substituents are attached.For example, (Rl)p ​​can be represented by, but not limited to, and can optionally be substituted as described here. In some embodiments, (R1), f or . In some embodiments,(r1)p is f . In some embodiments,(R )pé ^\.

[0076] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), R2 is selected from hydrogen, halogen, -OR15, -SR15, Petition 870250091144, dated 06 / 10 / 2025, p. 58 / 263 50 / 184 N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -N(R15)S(O)2R15, -C(O)OR15, OC(O)R15, -S(O)R15, -S(O)2R15, -NO2, -CN, and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, -NO2, =O, =S, =N(R15), and -CN. In some embodiments, R2 is selected from hydrogen, halogen, -OR15, SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -N(R15)S(O)2R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, -NO2, and -CN. In some embodiments, R2 is selected from C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, -NO2, =O, =S, =N(R15), and -CN. In some embodiments, R2 is selected from hydrogen, halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, -CN, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, R2 is selected from hydrogen, halogen, and C1-3 alkyl. In some embodiments, R2 is selected from hydrogen, halogen, methyl, and ethyl. In some embodiments, R2 is hydrogen.

[0077] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), R2 and R1 may link to form a 3- to 6-membered carbocycle, wherein the 3- to 6-membered carbocycle is optionally substituted with one or more independently selected halogen substituents, -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), -CN; C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, OR20, -N(R10)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), and -CN. In some embodiments, R2 and R1 can link to form a 3- to 6-membered carbocycle, wherein the 3- to 6-membered carbocycle is optionally substituted with one or more independently selected substituents. Petition 870250091144, dated 06 / 10 / 2025, p. 59 / 263 51 / 184 halogen, -OR21, -N(R21)2, -C(O)R21, -NO2, -CN; C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR21, -N(R21)2, -C(O)R21, NO2, and -CN. In some embodiments, R2 and R1 may link to form a 3- to 6-membered cycloalkyl, wherein the 3- to 6-membered cycloalkyl is optionally substituted with one or more independently selected halogen substituents, -OR21, -N(R21)2, -C(O)R21, -NO2, -CN; C1-6 alkyl and C3-6 cycloalkyl, each of which is optionally substituted with one or more independently selected halogen substituents, -OR21, N(R21)2, -C(O)R21, -NO2, and -CN.

[0078] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, N(R16)C(O)R16, -N(R16)S(O)2R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, NO2, -CN, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, C(O)R16, and -C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, S(O)2R16, -NO2, =O, =S, =N(R16), and -CN. In some embodiments, each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, N(R16)S(O)2R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, -NO2, and -CN.In some embodiments, each R3 is independently selected from each occurrence of C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR16, -SR16, -N(R16)2, -C(O)R16, and -C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, S(O)2R16, -NO2, =O, =S, =N(R16), and -CN. In some embodiments, each R3 is independently selected from each occurrence of hydrogen and C1-6 alkyl optionally substituted with one or more independent substituents. Petition 870250091144, dated 06 / 10 / 2025, page 60 / 263 52 / 184 selected halogens, -OR16, -SR16, -N(R16)2, -C(O)R16, and C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, NO2, =O, =S, =N(R16), and -CN. In some embodiments, each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -N(R16)2, -NO2, -CN, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, each R3 is independently selected in each occurrence of hydrogen and methyl. In some embodiments, each R3 is hydrogen.

[0079] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is -O-(CR'R'')m-(C3-10 carbocycle). In some embodiments, A is -O-(CR'R")m-(C3-10 carbocycle), where C3-10 carbocycle is optionally substituted saturated C3-10 carbocycle. In some embodiments, A is -O(CR'R'')m-(C3-10 carbocycle), where C3-10 carbocycle is optionally substituted unsaturated C3-10 carbocycle. In some embodiments, A is -O-(CR'R'')m(C3-10 carbocycle), where C3-10 carbocycle is selected from optionally substituted C3-4 carbocycle, optionally substituted C3-5 carbocycle, optionally substituted C3-6 carbocycle, optionally substituted C3-7 carbocycle, optionally substituted C3-8 carbocycle, and optionally substituted C3-9 carbocycle.In some embodiments, A is -O-(CR'R'')m-(C3-10 carbocycle), where C3-10 carbocycle is selected from optionally replaced C3 carbocycle, optionally replaced C4 carbocycle, optionally replaced C5 carbocycle, optionally replaced C6 carbocycle, optionally replaced C7 carbocycle, optionally replaced C8 carbocycle, optionally replaced C9 carbocycle, and optionally replaced C10 carbocycle.

[0080] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is -(CR'R'')m-(C3-10 carbocycle). In some embodiments, A is (CR'R'')m-(C3-10 carbocycle), where the C3-10 carbocycle is optionally substituted saturated C3-10 carbocycle. In some embodiments, A is -(CR'R'')m-(C310 carbocycle), where the C3-10 carbocycle is optionally substituted unsaturated C3-10 carbocycle. Petition 870250091144, dated 06 / 10 / 2025, p. 61 / 263 53 / 184 optionally replaced. In some embodiments, A is -(CR'R'')m-(C3-io carbocycle), wherein the C3-10 carbocycle is selected from optionally replaced C3-4 carbocycle, optionally replaced C3-5 carbocycle, optionally replaced C3-6 carbocycle, optionally replaced C3-7 carbocycle, optionally replaced C3-8 carbocycle, and optionally replaced C3-9 carbocycle. In some embodiments, A is -(CR'R'')m-(optionally replaced C3-10 carbocycle), wherein the optionally replaced C3-10 carbocycle is selected from optionally replaced C3 carbocycle, optionally replaced C4 carbocycle, optionally replaced C5 carbocycle, optionally replaced C6 carbocycle, optionally replaced C7 carbocycle, optionally replaced C8 carbocycle, optionally replaced C9 carbocycle, and optionally replaced C10 carbocycle.

[0081] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is optionally substituted C3-10 carbocycle. In some embodiments, A is optionally substituted saturated C3-10 carbocycle. In some embodiments, A is optionally substituted unsaturated C3-10 carbocycle. In some embodiments, A is selected from optionally substituted C3-4 carbocycle, optionally substituted C3-5 carbocycle, optionally substituted C3-6 carbocycle, optionally substituted C3-7 carbocycle, optionally substituted C3-8 carbocycle, and optionally substituted C3-9 carbocycle. In some embodiments, A is selected from optionally replaced C3 carbide cycle, optionally replaced C4 carbide cycle, optionally replaced C5 carbide cycle, optionally replaced C6 carbide cycle, optionally replaced C7 carbide cycle, optionally replaced C8 carbide cycle, optionally replaced C9 carbide cycle, and optionally replaced C10 carbide cycle.

[0082] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is an optionally substituted C3-6 carbocycle. In some embodiments, A is an optionally substituted saturated C3-6 carbocycle. In al Petition 870250091144, dated 06 / 10 / 2025, p. 62 / 263 54 / 184 In some embodiments, A is optionally substituted unsaturated C3-6 carbocycle. In some embodiments, A is selected from optionally substituted C3-5 carbocycle, optionally substituted C3-4 carbocycle, optionally substituted C4-6 carbocycle, and optionally substituted C5-6 carbocycle. In some embodiments, A is selected from optionally substituted C3 carbocycle, optionally substituted C4 carbocycle, optionally substituted C5 carbocycle, and optionally substituted C6 carbocycle.

[0083] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is -O-(CR'R'')m-(3- to 10-membered heterocycle). In some embodiments, A is -O-(CR'R'')m-(3- to 10-membered heterocycle), where the 3- to 10-membered heterocycle is an optionally substituted saturated 3- to 10-membered heterocycle. In some embodiments, A is -O-(CR'R'')m(3- to 10-membered heterocycle), where the 3- to 10-membered heterocycle is an optionally substituted unsaturated 3- to 10-membered heterocycle. In some embodiments, A is -O-(CR'R'')m-(heterocycle of 3 to 10 members), wherein the heterocycle of 3 to 10 members is selected from optionally substituted heterocycle of 3 to 4 members, optionally substituted heterocycle of 3 to 5 members, optionally substituted heterocycle of 3 to 6 members, optionally substituted heterocycle of 3 to 7 members, optionally substituted heterocycle of 3 to 8 members, and optionally substituted heterocycle of 3 to 9 members.In some embodiments, A is -O-(CR'R'')m(heterocycle of 3 to 10 members), wherein the heterocycle of 3 to 10 members is selected from optionally substituted 3-member heterocycle, optionally substituted 4-member heterocycle, optionally substituted 5-member heterocycle, optionally substituted 6-member heterocycle, optionally substituted 7-member heterocycle, optionally substituted 8-member heterocycle, optionally substituted 9-member heterocycle, and optionally substituted 10-member heterocycle. Petition 870250091144, dated 06 / 10 / 2025, page 63 / 263 55 / 184

[0084] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is -(CR'R")m-(3- to 10-membered heterocycle). In some embodiments, A is -(CR'R")m-(3- to 10-membered heterocycle), where the 3- to 10-membered heterocycle is an optionally substituted saturated 3- to 10-membered heterocycle. In some embodiments, A is -(CR'R'')m-(3- to 10-membered heterocycle), where the 3- to 10-membered heterocycle is an optionally substituted unsaturated 3- to 10-membered heterocycle. In some embodiments, A is -(CR'R'')m-(heterocycle of 3 to 10 members), wherein the heterocycle of 3 to 10 members is selected from optionally substituted heterocycle of 3 to 4 members, optionally substituted heterocycle of 3 to 5 members, optionally substituted heterocycle of 3 to 6 members, optionally substituted heterocycle of 3 to 7 members, optionally substituted heterocycle of 3 to 8 members, and optionally substituted heterocycle of 3 to 6 members.In some embodiments, A is -(CR'R'')m-(heterocycle of 3 to 10 members), wherein the heterocycle of 3 to 10 members is selected from optionally substituted 3-member heterocycle, optionally substituted 4-member heterocycle, optionally substituted 5-member heterocycle, optionally substituted 6-member heterocycle, optionally substituted 7-member heterocycle, optionally substituted 8-member heterocycle, optionally substituted 9-member heterocycle, and optionally substituted 10-member heterocycle.

[0085] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is a 3- to 10-membered heterocycle. In some embodiments, A is a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is an optionally substituted saturated 3- to 10-membered heterocycle. In some embodiments, A is a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is an optionally substituted unsaturated 3- to 10-membered heterocycle. In some embodiments, A is Petition 870250091144, dated 06 / 10 / 2025, p. 64 / 263 56 / 184 heterocycle of 3 to 10 members, wherein the heterocycle of 3 to 10 members is selected from optionally substituted heterocycle of 3 to 10 members, optionally substituted heterocycle of 3 to 5 members, optionally substituted heterocycle of 3 to 6 members, optionally substituted heterocycle of 3 to 7 members, optionally substituted heterocycle of 3 to 8 members, and optionally substituted heterocycle of 3 to 9 members. In some embodiments, A is heterocycle of 3 to 10 members, wherein the heterocycle of 3 to 10 members is selected from optionally substituted heterocycle of 3 members, optionally substituted heterocycle of 4 members, optionally substituted heterocycle of 5 members, optionally substituted heterocycle of 6 members, optionally substituted heterocycle of 7 members, optionally substituted heterocycle of 8 members, optionally substituted heterocycle of 9 members, and optionally substituted heterocycle of 10 members.

[0086] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is an optionally substituted 5- to 6-membered heteroaryl compound. In some embodiments, A is an optionally substituted 5- to 6-membered heteroaryl compound comprising at least one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, A is an optionally substituted 5- to 6-membered heteroaryl compound comprising at least one heteroatom of nitrogen or oxygen. In some embodiments, A is an optionally substituted 5- to 6-membered heteroaryl compound comprising at least one heteroatom of nitrogen or sulfur. In some embodiments, A is an optionally substituted 5- to 6-membered heteroaryl compound comprising at least one heteroatom of sulfur or oxygen. In some embodiments, A is an optionally substituted 5- to 6-membered heteroaryl compound comprising at least one heteroatom of sulfur.In some embodiments, A is an optionally substituted 5- to 6-membered heteroaryl group comprising at least one oxygen heteroatom. In some embodiments, A is a 5- to 6-membered heteroaryl group. Petition 870250091144, dated 06 / 10 / 2025, p. 65 / 263 57 / 184 members optionally replaced comprising at least one nitrogen heteroatom.

[0087] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from -O-(CR'R'')m-(3- to 10-membered heterocycle), and -O-(CR'R'')m-(C3-io carbocycle), the 3- to 10-membered heterocycle and C310 carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3. Ten carbocycles and heterocycles of 3 to 10 members are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0088] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), m is 0 and A is selected from -O-(heterocycle of 3 to 10 mem Petition 870250091144, dated 06 / 10 / 2025, p. 66 / 263 58 / 184 bros), and -O-(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0089] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), m is 1 and A is selected from -O-(CR'R'')-(3- to 10-membered heterocycle), and -O-(CR'R'')-(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents selected independently from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, Petition 870250091144, dated 06 / 10 / 2025, p. 67 / 263 59 / 184 C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0090] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from -(CR'R'')m-(3- to 10-membered heterocycle) and -(CR'R'')m-(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, Petition 870250091144, dated 06 / 10 / 2025, page 68 / 263 60 / 184 N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 3 to 10 members; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0091] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), m is 0 and A is selected from a 3- to 10-membered heterocycle and a C3-10 carbocycle, the 3- to 10-membered heterocycle and the C3-10 carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents Petition 870250091144, dated 06 / 10 / 2025, p. 69 / 263 61 / 184 selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0092] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), m is 1 and A is selected from -(CR'R'')-(3- to 10-membered heterocycle), and -(CR'R'')-(C3-io carbocycle), the 3- to 10-membered heterocycle and C310 carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3. Ten carbocycles and heterocycles of 3 to 10 members are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independent substituents. Petition 870250091144, dated 06 / 10 / 2025, p. 70 / 263 62 / 184 halogen separately selected, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0093] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from a saturated 5- to 6-membered C3-6 carbocycle and heteroaryl, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, -CN; and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and heterocycle of 3 to 10 members are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0094] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from a saturated 5- to 6-membered C3-6 carbocycle and heteroaryl, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, -CN; and C3-10 carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, Petition 870250091144, dated 06 / 10 / 2025, p. 71 / 263 63 / 184 C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0095] In some embodiments, for a compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from a saturated C3-6 carbocycle and a 5- to 6-membered heteroaryl group, any of which is optionally substituted with one or more substituents independently selected from: C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0096] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from a saturated C3-6 carbocycle and a 5- to 6-membered heteroaryl group, any of which is optionally substituted with one or more substituents independently selected from: Petition 870250091144, dated 06 / 10 / 2025, p. 72 / 263 64 / 184 halogen, -OR11, -N(R11)2, -C(O)R11, -NO2, -CN; C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -N(R11)2, -C(O)R11, -NO2, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C3-6 saturated carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -N(R11)2, -C(O)R11, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl.

[0097] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from C3-10 carbocycle and heteroaryl groups of 3 to 10 members, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3. Ten carbocycles and heterocycles of 3 to 10 members are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O,=S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,-N(R11)2,C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2,=O, Petition 870250091144, dated 06 / 10 / 2025, p. 73 / 263 65 / 184 = N(R11), e - CN.

[0098] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is a 5- to 6-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[0099] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is a 5- to 6-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, Petition 870250091144, dated 06 / 10 / 2025, p. 74 / 263 66 / 184 N(R11)S(O)2R11,-C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11,-NO2, -CN; and Optionally substituted C1-6 alkyl with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-6 saturated carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN.

[00100] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is a 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, and -CN. In some embodiments, A is a 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from: C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11, -SR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle; wherein the C3-6 carbocycle and 3- to 6-membered heterocycle are each optionally substituted with one or more substituents selected from: -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, Petition 870250091144, dated 06 / 10 / 2025, p. 75 / 263 67 / 184 - C(O)OR11, -OC(O)R11, -NO2, and -CN. In some embodiments, A is a 5- to 6-membered heteroaryl optionally substituted with one or more independently selected substituents of: C3-6 saturated carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[00101] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is a 5-membered heteroaryl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - C(O)OR11, -OC(O)R11, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, and -CN; and C3-6 saturated carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, Petition 870250091144, dated 06 / 10 / 2025, p. 76 / 263 68 / 184 - C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), e -CN.

[00102] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is a 5-membered heteroaryl optionally substituted with one or more substituents independently selected from: halogen, OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, and -CN. In some embodiments, A is a 5-membered heteroaryl optionally substituted with one or more substituents independently selected from: C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle; wherein the C3-6 carbocycle and 3- to 6-membered heterocycle are each optionally substituted with one or more substituents selected from: -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, OC(O)R11, -NO2, and -CN.In some embodiments, A is a 5-membered heteroaryl optionally substituted with one or more independently selected substituents of: C3-6 saturated carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[00103] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any of which is optionally substituted with C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, and -CN. In Petition 870250091144, dated 06 / 10 / 2025, page 77 / 263 69 / 184 In some embodiments, A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -NO2, and -CN. In some embodiments, A is selected from pyrazolyl optionally substituted with methyl, ethyl, isopropyl, and propyl. In some embodiments, A is selected from: '--''''n NI λ e / . In some modalities, A is n . In some modal- dades, A é / .

[00104] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is a 5-membered heteroaryl optionally substituted with a C3-10 carbocycle optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

[00105] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any of which is optionally substituted with a saturated C3-6 carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR11, N(R11)2, -C(O)R11, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl. Petition 870250091144, dated 06 / 10 / 2025, p. 78 / 263 70 / 184

[00106] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl are each optionally substituted with halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, A is selected from FF In some sports, A is not. In some sports, No. zN. In some modalities, A is ff.

[00107] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), B is -C(H)(R5)2. In some embodiments, each R5 is independently selected in each halogen occurrence, -OR13, -SR13, N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN. In some embodiments, each R5 is independently selected in each occurrence of C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN. In some embodiments, each R5 is independently selected at each occurrence of the C3-6 carbo-cycle optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​Petition 870250091144, dated 06 / 10 / 2025, p. 79 / 263 71 / 184 C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN. In some embodiments, each R5 is independently selected in each occurrence of C3-6 carbocycle optionally substituted with one or more substituents of C3-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), and -CN.

[00108] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), each R5 of -C(H)(R5)2 is independently selected from: halogen, -OR13, -N(R13)2, -C(O)R13, ​​-C(O)OR13, -NO2, -CN; C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -N(R13)2, -C(O)R13, ​​-C(O)OR13, -NO2, =O, =S, =N(R13), and -CN; and C3-10 carbocycle optionally substituted with one or more independently selected halogen substituents, -OR13, -N(R13)2, C(O)R13, ​​-C(O)OR13, -NO2, =O, =S, =N(R13), -CN, C1-6 alkyl, and C1-6 haloalkyl.

[00109] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), R5 is optionally substituted C3-10 carbocycle. In some embodiments, R5 is selected from optionally substituted C3-4 carbocycle, optionally substituted C3-5 carbocycle, optionally substituted C3-6 carbocycle, optionally substituted C3-7 carbocycle, optionally substituted C3-8 carbocycle, and optionally substituted C3-9 carbocycle. In some embodiments, R5 is selected from optionally substituted C4-10 carbocycle, optionally substituted C5-10 carbocycle, optionally substituted C6-10 carbocycle, optionally substituted C7-10 carbocycle, optionally substituted C8-10 carbocycle, and optionally substituted C9-10 carbocycle. In some embodiments Petition 870250091144, dated 06 / 10 / 2025, p. 80 / 263 72 / 184 embodiments, R5 is a saturated C3-10 carbocycle. In some embodiments, R5 is an optionally substituted unsaturated C3-10 carbocycle. In some embodiments, R5 is selected from an optionally substituted C3-6 carbocycle and an optionally substituted C6-10 carbocycle. In some embodiments, R5 is selected from an optionally substituted monocyclic C3-8 carbocycle and an optionally substituted bicyclic C6-10 carbocycle.

[00110] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), each R5 of -C(H)(R5)2 is independently selected from C3-6 carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR13, -N(R13)2, -C(O)R13, ​​-C(O)OR13, -NO2, =O, =S, =N(R13), -CN, C1-6 alkyl, and C1-6 haloalkyl.

[00111] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), B is an optionally substituted C3-10 carbocycle. In some embodiments, B is selected from optionally substituted C3-4 carbocycles, optionally substituted C3-5 carbocycles, optionally substituted C3-6 carbocycles, optionally substituted C3-7 carbocycles, optionally substituted C3-8 carbocycles, and optionally substituted C3-9 carbocycles. In some embodiments, B is selected from optionally substituted C4-10 carbocycles, optionally substituted C5-10 carbocycles, optionally substituted C6-10 carbocycles, optionally substituted C7-10 carbocycles, optionally substituted C8-10 carbocycles, and optionally substituted C9-10 carbocycles. In some embodiments, B is an optionally substituted saturated C3-10 carbocycle. In some embodiments, B is an optionally substituted unsaturated C3-10 carbocycle.In some embodiments, B is selected from an optionally substituted C3-6 carbcycle and an optionally substituted C6-10 carbcycle. In some embodiments, B is selected from an optionally substituted C3-8 carbcycle and an optionally substituted bicyclic C6-10 carbcycle. In some embodiments, B is selected from an optionally substituted monocyclic C3-7 carbcycle. Petition 870250091144, dated 06 / 10 / 2025, p. 81 / 263 73 / 184 replaced and C5-10 bicyclic carburetor optionally replaced.

[00112] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), B is C6-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR12, N(R12)2, -C(O)R12, -NO2, =O, =S, =N(R12), -CN; and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, N(R12)2, -C(O)R12, -NO2, =O, =S, =N(R12), and -CN. In some embodiments, B is C6-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR12, N(R12)2, -C(O)R12, -NO2, =O, =S, =N(R12), and -CN. In some embodiments, B is C6-10 carbocycle optionally substituted with one or more C1-6 alkyl groups optionally substituted with one or more independently selected halogen substituents, -OR12, N(R12)2, -C(O)R12, -NO2, =O, =S, =N(R12), and -CN.

[00113] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), B is selected from cyclohexyl and cycloheptyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, N(R12)2, -NO2, -CN, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, N(R12)2, -C(O)R12, -NO2, =O, =S, =N(R12), and -CN. In some embodiments, B is selected from cyclohexyl and cycloheptyl, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, B is optionally cyclohexyl substituted with one or more substituents independently selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, B is selected from: ^^T^, Petition 870250091144, dated 06 / 10 / 2025, p. 82 / 263 74 / 184 ά - Q 5 feff . In some modalities, B is I . In some modalities- des, B é f . In some modalities, B éFf .

[00114] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is optionally substituted C3-10 carbocycle. In some embodiments, ring D is optionally substituted C3-10 carbocycle, wherein the optional substituents of ring D are defined as in Formula (A) or Formula (I). In some embodiments, ring D is optionally substituted saturated C3-10 carbocycle. In some embodiments, ring D is optionally substituted unsaturated C3-10 carbocycle. In some embodiments, ring D is selected from optionally substituted C3-4 carbocycle, optionally substituted C3-5 carbocycle, optionally substituted C3-6 carbocycle, optionally substituted C3-7 carbocycle, optionally substituted C3-8 carbocycle, optionally substituted C3-9 carbocycle, and optionally substituted C3-10 carbocycle.In some embodiments, the D-ring is selected from optionally substituted C3 carbocycle, optionally substituted C4 carbocycle, optionally substituted C5 carbocycle, optionally substituted C6 carbocycle, optionally substituted C7 carbocycle, optionally substituted C8 carbocycle, optionally substituted C9 carbocycle, and optionally substituted C10 carbocycle. In some embodiments, the D-ring is selected from optionally substituted C3-8 monocyclic carbocycle, optionally substituted C5-10 bridging carbocycle, and C5-10 spirocycle carbocycle. In some embodiments, the D-ring is selected from optionally substituted C3-8 monocyclic carbocycle, optionally substituted C5-10 bridging carbocycle, and C5-10 spirocycle carbocycle, wherein the optional substituents for the D-ring are defined as. Petition 870250091144, dated 06 / 10 / 2025, p. 83 / 263 75 / 184 in Formula (A) or Formula (I).

[00115] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 3- to 10-membered heterocycle comprising at least one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, ring D is an optionally substituted 3- to 10-membered heterocycle comprising a nitrogen heteroatom, an oxygen heteroatom, or a sulfur heteroatom, or a combination thereof. In some embodiments, ring D is an optionally substituted saturated 3- to 10-membered heterocycle. In some embodiments, ring D is an optionally substituted 3- to 10-membered unsaturated heterocycle. In some embodiments, ring D is an optionally substituted 3- to 10-membered cycloalkyl heterocycle. In some embodiments, ring D is an optionally substituted 5- to 6-membered heteroaryl.In some embodiments, ring D is selected from optionally substituted 3- to 4-membered heterocycles, optionally substituted 3- to 5-membered heterocycles, optionally substituted 3- to 6-membered heterocycles, optionally substituted 3- to 7-membered heterocycles, optionally substituted 3- to 8-membered heterocycles, optionally substituted 3- to 9-membered heterocycles, and optionally substituted 3- to 10-membered heterocycles. In some embodiments, ring D is selected from optionally substituted 3-membered heterocycles, optionally substituted 4-membered heterocycles, optionally substituted 5-membered heterocycles, optionally substituted 6-membered heterocycles, optionally substituted 7-membered heterocycles, optionally substituted 8-membered heterocycles, optionally substituted 9-membered heterocycles, and optionally substituted 10-membered heterocycles.In some embodiments, the D ring is an optionally substituted 3- to 10-membered heterocycle, wherein the optional D ring substituents are defined as in Formula (A) or Formula (I). Petition 870250091144, dated 06 / 10 / 2025, p. 84 / 263 76 / 184

[00116] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is optionally substituted 3- to 10-membered heterocycloalkyl. In some embodiments, ring D is selected from optionally substituted 3- to 4-membered heterocycloalkyl, optionally substituted 3- to 5-membered heterocycloalkyl, optionally substituted 3- to 6-membered heterocycloalkyl, optionally substituted 3- to 7-membered heterocycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted 3- to 9-membered heterocycloalkyl, and optionally substituted 3- to 10-membered heterocycloalkyl.In some embodiments, ring D is selected from optionally substituted 3-membered heterocycloalkyl, optionally substituted 4-membered heterocycloalkyl, optionally substituted 5-membered heterocycloalkyl, optionally substituted 6-membered heterocycloalkyl, optionally substituted 7-membered heterocycloalkyl, optionally substituted 8-membered heterocycloalkyl, optionally substituted 9-membered heterocycloalkyl, optionally substituted 10-membered heterocycloalkyl. In some embodiments, ring D is optionally substituted 3- to 10-membered heterocycloalkyl, wherein the optional substituents of ring D are as defined in Formula (A) or Formula (I).

[00117] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 5- to 10-membered bicyclic heterocycle. In some embodiments, ring D is selected from an optionally substituted 5- to 6-membered bicyclic heterocycle, an optionally substituted 5- to 7-membered bicyclic heterocycle, an optionally substituted 5- to 8-membered bicyclic heterocycle, an optionally substituted 5- to 9-membered bicyclic heterocycle, and an optionally substituted 5- to 10-membered bicyclic heterocycle. In some embodiments, ring D is selected from an optionally substituted 5-membered bicyclic heterocycle, a bicyclic heterocycle Petition 870250091144, dated 06 / 10 / 2025, page 85 / 263 77 / 184 optionally substituted 6-membered heterocycle, optionally substituted 7-membered bicyclic heterocycle, optionally substituted 8-membered bicyclic heterocycle, optionally substituted 9-membered bicyclic heterocycle, and optionally substituted 10-membered bicyclic heterocycle. In some embodiments, the D-ring is an optionally substituted 5- to 10-membered bicyclic heterocycle, wherein the optional substituents of the D-ring are defined as in Formula (A) or Formula (I).

[00118] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 5- to 10-membered bicyclic heterocycle, wherein the optionally substituted 5- to 10-membered bicyclic heterocycle is selected from an optionally substituted 5- to 10-membered bridging heterocycle and an optionally substituted 5- to 10-membered spirocyclic heterocycle. In some embodiments, ring D is an optionally substituted 5- to 10-membered bicyclic heterocycle, wherein the optionally substituted 5- to 10-membered bicyclic heterocycle is selected from an optionally substituted 5- to 10-membered bridging heterocycle and an optionally substituted 5- to 10-membered spirocyclic heterocycle, wherein the optional substituents of ring D are defined as in Formula (A) or Formula (I).

[00119] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 5- to 10-membered bridging heterocycle. In some embodiments, ring D is selected from an optionally substituted 5- to 6-membered bridging heterocycle, an optionally substituted 5- to 7-membered bridging heterocycle, an optionally substituted 5- to 8-membered bridging heterocycle, an optionally substituted 5- to 9-membered bridging heterocycle, and an optionally substituted 5- to 10-membered bridging heterocycle. In some embodiments, ring D is selected from an optionally substituted 5-membered bridging heterocycle, an optionally substituted 6-membered bridging heterocycle, a heterocycle in Petition 870250091144, dated 06 / 10 / 2025, p. 86 / 263 78 / 184 optionally substituted 7-member bridge, optionally substituted 8-member bridge heterocycle, optionally substituted 9-member bridge heterocycle, and optionally substituted 10-member bridge heterocycle. In some embodiments, the D-ring is an optionally substituted 5- to 10-member bridge heterocycle, wherein the optional substituents of the D-ring are defined as in Formula (A) or Formula (I).

[00120] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 5- to 10-membered spirocyclic heterocycle. In some embodiments, ring D is selected from an optionally substituted 5- to 6-membered spirocyclic heterocycle, an optionally substituted 5- to 7-membered spirocyclic heterocycle, an optionally substituted 5- to 8-membered spirocyclic heterocycle, an optionally substituted 5- to 9-membered spirocyclic heterocycle, and an optionally substituted 5- to 10-membered spirocyclic heterocycle.In some embodiments, ring D is selected from optionally substituted 5-membered spirocyclic heterocycles, optionally substituted 6-membered spirocyclic heterocycles, optionally substituted 7-membered spirocyclic heterocycles, optionally substituted 8-membered spirocyclic heterocycles, optionally substituted 9-membered spirocyclic heterocycles, and optionally substituted 10-membered spirocyclic heterocycles. In some embodiments, ring D is optionally substituted 5- to 10-membered spirocyclic heterocycles, wherein the optional substituents of ring D are defined as in Formula (A) or Formula (I).

[00121] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the C3-10 carbocycle D ring is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, Petition 870250091144, dated 06 / 10 / 2025, p. 87 / 263 79 / 184 = N(R17), -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN.

[00122] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the C3-10 carbocycle D ring is optionally substituted with one or more independently selected halogen substituents, -OR17, SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN. In some embodiments, ring D is a C3-10 carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00123] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the D ring is C3-10 carbocycle optionally substituted with one or more independently selected C1-10 alkyl substituents optionally substituted with one or more independently selected substituents Petition 870250091144, dated 06 / 10 / 2025, p. 88 / 263 80 / 184 halogenated compounds, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, =O, =S, =N(R17), and -CN. In some embodiments, ring D is a C3-10 carbocycle optionally substituted with one or more independently selected substituents of C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17); and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00124] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a C3-10 carbocycle optionally substituted with one or more independently selected substituents of C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, =O, =S, =N(R17), and -CN.In some embodiments, ring D is a C3-10 carbocycle optionally substituted with one or more independently selected substituents of C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, Petition 870250091144, dated 06 / 10 / 2025, page 89 / 263. 81 / 184 SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00125] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the C3-10 carbocycle D ring is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN.

[00126] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the C3-10 carbocycle D ring is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00127] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the D ring is a C3-10 saturated carbocycle optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, Petition 870250091144, dated 06 / 10 / 2025, p. 90 / 263 82 / 184 N(R17)S(O)2R17,-C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17,-NO2, -CN; and C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle. In some embodiments, ring D is a saturated C3-6 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl.In some embodiments, ring D is a saturated C3-6 carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00128] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocyclo. In some embodiments, ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, ring D is selected \ <X Oy X de: 7 , / , e - . Em algumas modalidades, o anel D é . Em algumas modalidades, o anel D é Em algumas modalidades, o anel D Petition 870250091144, dated 06 / 10 / 2025, p. 91 / 263 83 / 184 and

[00129] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; C1-io alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN.

[00130] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; Petition 870250091144, dated 06 / 10 / 2025, p. 92 / 263 84 / 184 C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00131] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN.

[00132] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: Petition 870250091144, dated 06 / 10 / 2025, p. 93 / 263 85 / 184 halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00133] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from a 3- to 7-membered monocyclic heterocycle and a 5- to 10-membered bicyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN. Petition 870250091144, dated 06 / 10 / 2025, p. 94 / 263 86 / 184

[00134] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from a 3- to 7-membered monocyclic heterocycle and a 5- to 10-membered bicyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00135] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from a 3- to 7-membered monocyclic heterocycle and a 5- to 10-membered bicyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, Petition 870250091144, dated 06 / 10 / 2025, p. 95 / 263 87 / 184 N(R17)S(O)2R17,-C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17,-NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN.

[00136] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from a 3- to 7-membered monocyclic heterocycle and a 5- to 10-membered bicyclic heterocycle, any of which is optionally substituted with one or more independently selected substituents: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00137] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 5- to 6-membered heteroaryl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and Petition 870250091144, dated 06 / 10 / 2025, p. 96 / 263 88 / 184 R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00138] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, ring D is a 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.In some embodiments, ring D is selected from pyridinyl and pyrimidinyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, ring D is selected from... In some forms, the D-ring is In some disciplines, the D-ring is

[00139] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from saturated 3- to 6-membered heterocycles and unsaturated 3- to 6-membered heterocycles, either of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, Petition 870250091144, dated 06 / 10 / 2025, p. 97 / 263 89 / 184 N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00140] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 3- to 6-membered unsaturated heterocycle with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00141] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from 3- to 6-membered heterocycloalkyl optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, -CN; and Petition 870250091144, dated 06 / 10 / 2025, p. 98 / 263 90 / 184 C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00142] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), Ring D is selected from saturated 3- to 6-membered heterocycles and unsaturated 3- to 6-membered heterocycles, either of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle. In some embodiments, ring D is selected from saturated 3- to 6-membered heterocycles and unsaturated 3- to 6-membered heterocycles, either of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle; and R17 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

[00143] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 3- to 6-membered unsaturated heterocycle with one or more substituents independently selected from halogen, C1-6 haloalkyl, and C3-6 carbocycle. In some embodiments, ring D is selected from 2,5-dihydrofuranyl and 3,6-dihydro-2H-pyranyl. <°Ί In some modalities, the D ring is selected from e'. In some modalities, the D ring is '. In some modalities, the D ring Petition 870250091144, dated 06 / 10 / 2025, p. 99 / 263 91 / 184

[00144] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 3- to 6-membered heterocycloalkyl optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocyclo. In some embodiments, ring D is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyran, dioxanyl, morpholinyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl and C3-6 carbocycle; and R17 is selected from hydrogen, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle. In some embodiments, ring D is selected In some models, the D-ring is selected. Petition 870250091144, dated 06 / 10 / 2025, p. 100 / 263 92 / 184 in some embodiments, the D ring is selected- swimming In some sports, the ring D is selected from

[00145] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 5- to 10-membered bicyclic heterocycle selected from a 5- to 10-membered bridging heterocycle and a 5- to 10-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN. Petition 870250091144, dated 06 / 10 / 2025, p. 101 / 263 93 / 184

[00146] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 5- to 10-membered bicyclic heterocycle selected from a 5- to 10-membered fused heterocycle, a 5- to 10-membered bridging heterocycle, and a 5- to 10-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle.

[00147] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 5- to 10-membered fused heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haO, NI, N / I alkyl, and C3-6 carbocycle. In some embodiments, ring D is .

[00148] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is a 5- to 10-membered bicyclic heterocycle selected from a 5- to 10-membered bridging heterocycle and a 5- to 10-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from halogen, OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle.

[00149] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the 5- to 10-membered bicyclic heterocycle of ring D is a 5- to 10-membered bridging heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independent substituents Petition 870250091144, dated 06 / 10 / 2025, p. 102 / 263 94 / 184 halogen substituents selected, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, and -CN. In some embodiments, ring D is a 5- to 10-membered bridged heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, -N(R17)2, C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle. In some embodiments, ring D is a 5- to 10-membered bridging heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR17, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, ring D is selected from 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa 5-azabicyclo[2.2.1]heptanil, and 8-oxa-3-azabicyclo[3.2.1]octanyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, ring D is selected from In some models, the D-ring is In some forms, the D-ring is In some forms, the D-ring is

[00150] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), the 5- to 10-membered bicyclic heterocycle of ring D is a 5- to 10-membered spirocyclic heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, Petition 870250091144, 06 / 10 / 2025, p. 103 / 263 95 / 184 C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN. In some embodiments, ring D is a 5- to 10-membered spirocyclic heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle. In some embodiments, ring D is a 5- to 10-membered spirocyclic heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, ring D is selected from 2-oxa-6-azaspiro[3.3]heptanyl, 6-oxa-2-azaspiro[3.5]nonaniyl, 7-oxa-2-azaspiro[3.5]nonaniyl, 2-oxa-6-azaspiro[3.4]octanyl, 4-oxa-7azaespiro[2.5]octanyl, and 4-methyl-4,7-diazaespiro[2.5]octanyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, C1-3 alkyl, and C1-3 haloalkyl. In some embodiments, ring D is selected from: and -7. In some forms, the D ring is In some models, the D-ring is In some forms, the D-ring is In some Petition 870250091144, dated 06 / 10 / 2025, p. 104 / 263 96 / 184 modalities, the D ring is O > k^ / N^y ' In some embodiments, the D-ring is either selected from or the D-ring is selected from

[00151] In some embodiments, for the compound or salt of Formula (A), ,,, and ,,,,

[00152] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), ring D is selected from Petition 870250091144, dated 06 / 10 / 2025, p. 105 / 263 97 / 184

[00153] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, and R21 are each independently selected at each occurrence of hydrogen.

[00154] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, and R21 are each independently selected at each occurrence of: hydrogen; and Optionally substituted C1-6 alkyl with one or more independently selected halogen substituents, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, -O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted. Petition 870250091144, dated 06 / 10 / 2025, p. 106 / 263 98 / 184 individually substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN.

[00155] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, and R21 are each independently selected at each occurrence of: hydrogen; and C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN.

[00156] In some embodiments, for the compound or salt of Formula (A), (I), (Ia), or (Ib), R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, and R21 are each independently selected from each occurrence of hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 carbocycle, and 3- to 6-membered heterocycle.

[00157] In another aspect, the present invention provides a compound or salt having the structure selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, p. 107 / 263 99 / 184 F

[00158] Although preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, alterations, and substitutions will now 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 employed in the practice of the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents are covered by them.

[00159] Chemical entities with carbon-carbon double bonds or carbon-nitrogen double bonds may exist in the Z or E form (or in the cis or trans form). In addition, some chemical entities may exist in various tautomeric forms. Unless otherwise indicated, compounds or salts of Formula (A), (I), (Ia) or (Ib) must include all Z, E and tautomeric forms.

[00160] “Isomers” are different compounds that have the same molecular formula. “Stereoisomers” are isomers that differ only in the way the atoms are arranged 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. “Diastereomers” are stereoisomers that have at least one atom in common. Petition 870250091144, dated 06 / 10 / 2025, page 108 / 263 100 / 184 minus two asymmetric atoms, but they 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 R or S. Resolved compounds whose absolute configuration is unknown can be designated (+) or (-), depending on the direction (dextrorotatory or levorotatory) in which they rotate in plane-polarized light at the sodium D-line wavelength. Certain compounds described here contain one or more asymmetric centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms, whose asymmetric centers can be defined, in terms of absolute stereochemistry, as (R)- or (S)-.The present chemical entities, pharmaceutical compositions, and methods are intended 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 by any suitable method, including, but not limited to, chiral chromatography and polarimetry, and the degree of predominance of one stereoisomer over the other isomer can be determined.

[00161] The compounds or salts of Formula (A), (I), (Ia) or (Ib) may, in some cases, exist as diastereomers, enantiomers or other stereoisomeric forms. The compounds presented here include all diastereomeric, enantiomeric and epimeric forms, as well as racemates, mixtures of diastereomers and other mixtures thereof, insofar as they may be obtained by a person skilled in the art through routine experimentation. The separation of stereoisomers may be carried out by chromatography or by the formation of diastereomers and separation by recrystallization, or cro Petition 870250091144, dated 06 / 10 / 2025, page 109 / 263 101 / 184 chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981, incorporated herein by reference to this invention). Stereoisomers can also be obtained by stereoselective synthesis. Furthermore, a mixture of two enantiomers enriched in one of the two can be purified to provide an optically enriched form of the principal enantiomer by recrystallization and / or trituration.

[00162] In certain embodiments, compounds or salts to Formula (A), (I), (Ia) or (Ib) may comprise two or more enantiomers or diastereomers of a compound wherein a single enantiomer or diastereomer represents 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 of producing substantially pure enantiomers are well known to those skilled in the art. For example, a single stereoisomer, for example, an enantiomer, substantially free of its stereoisomer can be obtained by resolving the racemic mixture using a method 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 diastereomeric ionic salts with chiral compounds and separation by fractional crystallization or other methods; (2) formation of diastereomeric compounds with chiral derivatizing reagents, separation of the diastereomers and conversion to pure stereoisomers; and (3) separation of the substantially pure or enriched stereoisomers directly under chiral conditions. Another approach to the separation of enantiomers is to use a chi-column. Petition 870250091144, dated 06 / 10 / 2025, page 110 / 263 102 / 184 ral Diacel and elute using an organic mobile phase, as done by Chiral Technologies (www.chiraltech.com) on a fee-per-service basis.

[00163] A tautomer refers to a molecule in which it is possible for a proton to be transferred from one atom to another atom within the same molecule. In certain embodiments, compounds or salts of Formula (A), (I), (Ia), or (Ib) exist as tautomers. Under circumstances where tautomerization is possible, a chemical equilibrium of tautomers may exist. The exact proportion of tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some non-limiting examples of tautomeric equilibrium include:

[00164] The compounds of Formula (A), (I), (Ia) or (Ib) may be used in different enriched isotopic forms, for example, enriched with 2H, 3H, 11C, 13C and / or 14C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms may be produced by the procedure described in U.S. Patent Nos. Petition 870250091144, dated 06 / 10 / 2025, p. 111 / 263 103 / 184 5,846,514 and 6,334,997. As described in U.S. Patents Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thereby increasing the duration of action of medications.

[00165] In certain embodiments, compounds of Formula (A), (I), (Ia) or (Ib) have some or all of the 1H atoms replaced by 2H atoms. The synthesis methods for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.

[00166] Deuterium-substituted compounds are synthesized using various methods, as 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.

[00167] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to enable the synthesis of deuterium-containing compounds. A large number of deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[00168] Unless otherwise indicated, the compounds of Formula (A), (I), (Ia) or (Ib) are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds with the structures shown, except for the substitution of a hydrogen by a deuterium or tritium, or by the substitution of a carbon by a carbon enriched with 13C or 14C, are within the scope of the present invention. Petition 870250091144, dated 06 / 10 / 2025, p. 112 / 263 104 / 184

[00169] Compounds of Formula (A), (I), (Ia) or (Ib) optionally contain unnatural proportions of atomic isotopes in one or more of their constituent atoms. For example, compounds may be labeled with isotopes such as, for example, deuterium (2H), tritium (3H), iodine-125 (125I) or carbon-14 (14C). Isotopic substitution of I with 2H, 11C, 13C, 14C, 15C, 12N, 13N, 15N, 16N, 16O, 17O, 14F, 15F, 16F, 17F, 18F, 33S, 34S, 35S, 36S, 35Cl, 37Cl, 79Br, 81Br and 125I are all contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are within the scope of the present invention.

[00170] Included in the present invention are salts, particularly pharmaceutically acceptable salts, of the compounds of Formula (A), (I), (Ia) or (Ib). The compounds of the present invention may possess a sufficiently acidic functional group, a sufficiently basic functional group or both, and may react with any of a series of inorganic bases and inorganic and organic acids to form a salt. Alternatively, compounds that are inherently charged, such as those with quaternary nitrogen, may form a salt with an appropriate counterion, for example, a halide such as bromide, chloride or fluoride.

[00171] In certain embodiments, compounds or salts of Formula (A), (I), (Ia) or (Ib) may be prodrugs. The term prodrug encompasses compounds that, under physiological conditions, are converted into the pharmaceutical agents of the present invention. One method for producing 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 an enzymatic activity of the host animal, such as specific target cells in the host animal.

[00172] In some embodiments, the design of a prodrug increases the lipophilicity of the pharmaceutical agent. In some embodiments, the design of Petition 870250091144, dated 06 / 10 / 2025, p. 113 / 263 105 / 184 a prodrug increases effective solubility in water. 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 Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, all incorporated herein for such invention). According to another embodiment, the present invention provides methods 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.

[00173] The transformations and methodologies of synthetic chemistry useful in the synthesis of the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, 2nd 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). Pharmaceutical Formulations

[00174] In some respects, the present invention provides a pharmaceutical composition comprising a compound or salt of Formula (A), (I), (Ia) or (Ib) and at least one pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises a compound or salt of Formula (A), (I), (Ia) or (Ib) and a pharmaceutically acceptable excipient.

[00175] In some respects, the present invention provides a pharmaceutical composition comprising a compound selected from the group that consists of Petition 870250091144, dated 06 / 10 / 2025, page 114 / 263 106 / 184 you in or a pharmaceutically acceptable version of either of them, and a pharmaceutically acceptable excipient.

[00176] Pharmaceutical compositions can be formulated using one or Petition 870250091144, dated 06 / 10 / 2025, page 115 / 263 107 / 184 plus physiologically acceptable carriers, including excipients and auxiliaries. The formulation may be modified depending on the chosen route of administration. Pharmaceutical compositions comprising a compound, salt or conjugate may be manufactured, for example, by lyophilizing the compound, salt or conjugate, mixing, dissolving, emulsifying, encapsulating or trapping the conjugate. Pharmaceutical compositions may also include the compounds, salts or conjugates in a free base form or in a pharmaceutically acceptable salt form.

[00177] Pharmaceutical compositions may also comprise more than one active compound (for example, a compound, salt or conjugate and other agents), as necessary for the specific indication to be treated. The active compounds may have complementary activities that do not adversely affect each other. Such molecules may be present in combination in amounts effective for the intended purpose.

[00178] A compound or salt of any of Formulas (A), (I), (Ia) or (Ib) may be formulated into any suitable pharmaceutical formulation. A pharmaceutical formulation of this invention typically contains an active ingredient (e.g., compound or salt of any of Formulas (A) or (I)) and one or more pharmaceutically acceptable excipients or carriers, including, but not limited to: diluents and inert solid fillers, diluents, sterile aqueous solution and various organic solvents, permeation enhancers, antioxidants, solubilizers and adjuvants.

[00179] In certain embodiments, a compound or salt of Formula (A), (I), (Ia) or (Ib) is formulated with a chelating agent or other material capable of binding metal ions, such as ethylenediaminetetraacetic acid (EDTA) and its salts are capable of increasing the stability of a compound or salt of Formula (A), (I), (Ia) or (Ib).

[00180] Pharmaceutical formulations can be supplied in any Petition 870250091144, dated 06 / 10 / 2025, page 116 / 263 108 / 184 appropriate form, which may depend on the route of administration.

[00181] In some embodiments, the invention provides a pharmaceutical composition for oral administration containing at least one compound or salt of any of Formulas (A), (I), (Ia) or (Ib) and a pharmaceutical excipient suitable for oral administration. The composition may be in solid, liquid, gel, semi-liquid or semi-solid form. In some embodiments, the composition further comprises a second agent.

[00182] The pharmaceutical compositions of the present invention, suitable for oral administration, may be presented as discrete pharmaceutical forms, such as hard or soft capsules, capsules, lozenges, tablets or pills, or liquids or aerosols, each containing a predetermined amount of an active ingredient in the form of powder or granules, solution or suspension in aqueous or non-aqueous liquid, oil-in-water emulsion, water-in-oil liquid emulsion, dispersible powders or granules, syrups or elixirs. Such pharmaceutical forms may be prepared by any of the pharmaceutical methods, which normally include the step of combining the active ingredient(s) with the vehicle. In general, the compositions are prepared by uniformly and intimately mixing the active ingredient(s) with liquid vehicles or finely divided solid vehicles, or both, and then, if necessary, molding the product into the desired presentation.For example, a tablet may be prepared by compression or molding, optionally with one or more accessory ingredients. Pressed tablets may be prepared by compressing, in a suitable machine, the active ingredient(s) in a fluid form, such as powder or granules, optionally mixed with an excipient, such as, inter alia, a binder, a lubricant, an inert diluent and / or a surfactant or dispersing agent. Molded tablets may be produced by molding, in a suitable machine, a mixture of the powder or salt compound of any of Formulas (A), (I),. Petition 870250091144, dated 06 / 10 / 2025, page 117 / 263 109 / 184 (Ia) or (Ib), moistened with an inert liquid diluent.

[00183] Pharmaceutical compositions may also be prepared from a compound or salt of any of Formulas (A), (I), (Ia) or (Ib) and one or more pharmaceutically acceptable excipients. Preparations for such pharmaceutical compositions are well known in the art. See, 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 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). TREATMENT METHODS

[00184] In some respects, the present invention provides a method of modulating IL-17 A in an individual in need thereof, comprising administering to the individual a compound or salt of Formula (A), (I), (Ia) or (Ib), or a pharmaceutical composition thereof.

[00185] Elevated 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 patients with RA. IL-17A exerts its role in the pathogenesis of RA through IL-1β- and TNF-α-dependent and independent pathways. IL-17A stimulates the secretion of other cytokines and chemokines, for example, Petition 870250091144, dated 06 / 10 / 2025, p. 118 / 263 110 / 184 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 the mouse knee promotes joint destruction independently of IL-1β activity (Ann Rheum Dis 2000, 59: 529-32). Anti-IL-1β antibody has no effect on IL-17A-induced inflammation and joint damage (J. Immunol 2001, 167:1004-1013). In a murine streptococcal cell wall-induced arthritis (SCW) model, IL-17A induced inflammatory cell infiltration and proteoglycan depletion in wild-type and knockout mice for IL1β and TNF-α. IL-17A knockout mice are phenotypically normal in the absence of antigenic challenge, but exhibit markedly reduced arthritis after immunization with type II collagen (J. Immunol 2003, 171:6173-6177). Increased levels of IL-17A-secreting cells have also been observed in the facet joints of patients suffering from ankylosing spondylitis (H Appel et al.)., Arthritis Res Therap. 2011, 13:R 95).

[00186] Multiple sclerosis is an autoimmune disease characterized by inflammation of the central nervous system (CNS) with damage to the myelin sheath surrounding axons. A hallmark of MS is T-cell infiltration in the CNS. Higher numbers of blood mononuclear cells (MNCs) expressing IL-17A mRNA are detected during clinical exacerbation of MS compared to remission (Multiple Sclerosis, 5:101-104, 1999). Furthermore, experimental autoimmune encephalomyelitis (“EAE”), a preclinical animal model for MS, is significantly suppressed in IL-17A-deficient mice.

[00187] In certain aspects, the invention provides methods for modulating IL-17A in an individual in need, comprising administering to said individual a compound or salt of Formula (A), (I), (Ia) or (Ib). In certain embodiments, a compound or salt of Formula (A), (I), (Ia) or (Ib) inhibits IL-17A activity in an individual in need thereof. Petition 870250091144, dated 06 / 10 / 2025, p. 119 / 263 111 / 184

[00188] In certain embodiments, a compound or salt of Formula (A), (I), (Ia), or (Ib) may be used to treat or prevent a disease or condition directly or indirectly mediated 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 involve administering therapeutically effective amounts of the compounds described herein or a pharmaceutical composition thereof to the individual. 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.

[00189] In some respects, the present invention provides a method for treating or preventing an inflammatory disease or condition in an individual in need, comprising administering to the individual a compound or salt of Formula (A), (I), (Ia) or (Ib), or a pharmaceutical composition thereof. In certain embodiments, a compound or salt of Formula (A), (I), (Ia) or (Ib) is administered to an individual in need thereof to treat an inflammatory disease or condition, for example, psoriasis.

[00190] In certain embodiments, a compound or salt of Formula (A), (I), (Ia) or (Ib) is used to treat or prevent a selected inflammatory disease or condition 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. In certain embodiments, a compound or salt of Formula (A), (I), (Ia) or (Ib) is used to treat or prevent psoriasis. In certain embodiments, a compound or salt of Formula (A), (I), (Ia) or (Ib) is used for the treatment or prevention of a condition including, but not limited to Petition 870250091144, dated 06 / 10 / 2025, pp. 120 / 263 112 / 184 limiting, airway inflammation, ankylosing spondylitis, asthma, RA (including juvenile RA), as well as other inflammatory disorders, conditions or diseases.

[00191] In certain respects, the invention provides methods of modulating IL-17A in an individual in need thereof, comprising administering to said individual a compound selected from the group consisting of: F F ,, F F, and, or a pharmaceutically acceptable salt of any of them. In certain modalities, the compound is selected from the group consisting of: F Petition 870250091144, dated 06 / 10 / 2025, pp. 121 / 263 113 / 184 A pharmaceutically acceptable salt of either of these inhibits IL-17A activity in an individual in need of it.

[00192] In certain embodiments, a compound selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 122 / 263 114 / 184 A pharmaceutically acceptable salt of any of these compounds can be used to treat or prevent a disease or condition directly or indirectly mediated 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 involve administering therapeutically effective amounts of the compounds described herein or a pharmaceutical composition thereof to the individual. 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.

[00193] In some respects, the present invention provides a method of treating or preventing an inflammatory disease or condition in an individual in need thereof, comprising administering to the individual a compound or salt selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 123 / 263 115 / 184 f, ef, or a pharmaceutical composition of either of them. In some embodiments, the compound or salt is selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 124 / 263 116 / 184 \__ / K ,-k^NH FF F^lef is administered to an individual who needs it to treat an inflammatory disease or condition, for example, psoriasis.

[00194] In certain embodiments, a compound or salt selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 125 / 263 117 / 184 FIF l FI , f , f , ef , e is used to treat or prevent a selected inflammatory disease or condition among 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. In some embodiments, the compound or salt is selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 126 / 263 118 / 184 To treat or prevent psoriasis. In some forms, the compound or salt is selected from the group that consists of Petition 870250091144, dated 06 / 10 / 2025, pp. 127 / 263 119 / 184 It is used for the treatment or prevention of a condition including, but not limited to, airway inflammation, ankylosing spondylitis, asthma, rheumatoid arthritis (including juvenile rheumatoid arthritis), as well as other inflammatory disorders, conditions or diseases.

[00195] In certain aspects, the present invention provides methods of treating psoriasis using a compound or salt, as described herein. In some embodiments, the method of treating psoriasis comprises administering to an individual in need a compound or salt, as described herein. In some embodiments, the method of treating psoriasis comprises administering to an individual in need thereof a compound or salt of Formula (A), (I), (Ia) or (Ib). In some embodiments, the method of treating psoriasis comprises administering to an individual in need thereof a pharmaceutical composition comprising a compound or salt of Formula (A), (I), (Ia) or (Ib) and a pharmaceutically acceptable excipient. In some embodiments, the method of treating psoriasis comprises administering to an individual in need thereof Petition 870250091144, dated 06 / 10 / 2025, pp. 128 / 263 120 / 184 even of a compound or salt selected from the group consisting of: In some modalities, the method of treating psoriasis involves administering to an individual in need a pharmaceutical composition comprising a compound or salt selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 129 / 263 121 / 184 mathematically acceptable. , and an excipient far

[00196] In certain aspects, the present invention provides methods of treating psoriatic arthritis using a compound or salt, as described herein. In some embodiments, the method of treating psoriatic arthritis comprises administering to an individual in need thereof a compound or salt, as described herein. In some embodiments, the method of treating psoriatic arthritis comprises administering to an individual in need thereof a compound or salt of Formula (A), (I), (Ia) or (Ib). In some embodiments, the method of treating psoriatic arthritis Petition 870250091144, dated 06 / 10 / 2025, pp. 130 / 263 122 / 184 comprises administering to an individual in need thereof a pharmaceutical composition comprising a compound or salt of Formula (A), (I), (Ia) or (Ib) and a pharmaceutically acceptable excipient. In some embodiments, the method of treatment of psoriatic arthritis comprises administering to an individual in need thereof a compound or salt selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 131 / 263 123 / 184 In some modalities, the treatment method for psoriatic arthritis involves administering to an individual in need a pharmaceutical composition comprising a compound or salt. selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 132 / 263 124 / 184 and a pharmaceutically acceptable excipient.

[00197] In certain aspects, the present invention provides methods for treating ankylosing spondylitis using a compound or salt as described herein. In some embodiments, the method for treating ankylosing spondylitis comprises administering to an individual in need thereof a compound or salt as described herein. In some embodiments, the method for treating ankylosing spondylitis comprises administering to an individual in need thereof a compound or salt of Formula (A), (I), (Ia) or (Ib). In some embodiments, the method for treating ankylosing spondylitis comprises administering to an individual in need thereof a pharmaceutical composition comprising a compound or salt of Formula (A), (I), (Ia) or (Ib) and a pharmaceutically acceptable excipient. In some embodiments, the method for treating ankylosing spondylitis comprises administering to an individual in need thereof a compound or salt selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pp. 133 / 263 125 / 184 In some modalities, the method of treatment for ankylosing spondylitis involves administering to an individual in need a pharmaceutical composition comprising a compound or salt selected from the group that F, _ F consists of: Petition 870250091144, dated 06 / 10 / 2025, pp. 134 / 263 126 / 184 FIFIFI f , f , ef , and a pharmaceutically acceptable excipient. EXAMPLES

[00198] The invention is now described in general terms and will be more easily understood by reference to the following examples, which are included only for the purpose of illustrating certain aspects and embodiments of the present invention and are not intended to limit the invention in any way.

[00199] The following synthetic schemes are provided for illustrative, not limiting, purposes. The following examples illustrate the various methods of producing compounds described in this document. It is understood that one skilled in the art may be able to produce these compounds by similar methods or by combining other methods known to one skilled in the art. It is also understood that one skilled in the art would be able to produce them in a manner similar to that described below, using appropriate starting materials and modifying the synthetic route as necessary. In general, starting materials and reagents may be obtained from commercial suppliers or synthesized according to sources known to one skilled in the art or prepared as described in this document.

[00200] Examples 1 to 25 show exemplary procedures for the preparation of the claimed IL-17A modulators. Example 26 provides IC50 inhibition data from the IL-17 A / A bioassay.

[00201] Example 1: General synthesis procedures 1 to 6 General Procedure 1 Petition 870250091144, dated 06 / 10 / 2025, pp. 135 / 263 127 / 184 RR / =N% Λd·· B(OMe)3, DIEA)= R'—£χΝ+Brx^|< -----------►R'—4 '--( O THF '4 Jl NH2N^R 23

[00202] To a solution of aminopyridazine 1 (1.00 eq.) and bromoketone 2 (1.00-1.20 eq.) in tetrahydrofuran, Λ / ,ΛZ-diisopropylethylamine (5.00-10.0 eq.) and trimethyl borate (5.00-10.0 eq.) were added. The reaction mixture was stirred at 70 °C for 1 to 3 h. The reaction mixture was then diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water and then with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide a residue, which was then purified by preparative TLC, column chromatography, preparative HPLC, and / or preparative SFC to provide imidazo[1,2-b]pyridazine 3. General Procedure 2 5

[00203] To a solution of primary amine 4 protected by Cbz (1.00 eq.) in dichloromethane, iodotrimethylsilane (1.50 to 8.55 eq.) was added at 0°C. The mixture was stirred at 0°C for 2 h. The reaction mixture was diluted with a 1.0 M aqueous solution of hydrochloric acid and washed with ethyl acetate. The aqueous phase was adjusted to pH = 8 to 9 with a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide free primary amine 5. General Procedure 3 Petition 870250091144, dated 06 / 10 / 2025, pp. 136 / 263 128 / 184 H2, Pd / C R R 5

[00204] To a solution of primary amine 4 protected by Cbz (1.00 eq.) in tetrahydrofuran, dichloromethane and / or methanol (optionally with NH3 · H2O additive), Pd / C (10.0% purity) was added under a N2 atmosphere. The suspension was degassed and purged with H2 three times. The mixture was stirred under H2 (15 psi) at 25°C for 1 to 20 h. The reaction mixture was filtered and then concentrated under reduced pressure to provide the free primary amine 5. General Procedure 4 EDCI 6

[00205] A solution of primary amine 5 (1.00 eq.), carboxylic acid 6 (1.20-3.00 eq.) and EDCI (2.00-3.00 eq.) in pyridine was stirred at room temperature for 1 to 18 h. The reaction mixture was then diluted with water and extracted with ethyl acetate. The combined organic layers were optionally washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to provide a residue, which was purified by preparative TLC, column chromatography, preparative HPLC and / or preparative SFC to provide amide 7. General Procedure 5 Petition 870250091144, dated 06 / 10 / 2025, pp. 137 / 263 129 / 184 ixF Br. / B F. F - F' / R-NH k+ R * / |X 1) THF 2) K2CO3, acetoneR

[00206] To a solution of potassium (bromomethyl)trifluoroborate (1.00 eq.) in THF (100 mL) was added amine 8 (8.15 eq.). The reaction mixture was stirred at 80°C for 0.5 h. The reaction mixture was concentrated under reduced pressure to provide a residue to which potassium carbonate (1.04 eq.) was added. The reaction mixture was stirred again at 25°C for 0.5 h. The reaction mixture was filtered with ethyl acetate and the filtrate was concentrated under reduced pressure to provide a residue which was triturated with acetone and petroleum ether (1 / 10) at 25°C for 5 min to provide potassium trifluoro(aminomethyl)borate 9. General Procedure 6 11 12

[00207] To a solution of aldehyde 10 (1.00 eq.) and amine 11 (10.0 eq.) in methanol, NaBHsCN (3.00 eq.) and AcOH (1.00 eq.) or NaOAc (6.00 eq.) were added. The reaction mixture was stirred at 25°C for 1 h. The reaction mixture was filtered with MeOH and the filtrate was concentrated under reduced pressure to provide a residue that was purified by preparative TLC, column chromatography, preparative HPLC and / or preparative SFC to produce amine 12. Example 2. General Scheme - Synthesis of Intermediate A Petition 870250091144, dated 06 / 10 / 2025, pp. 138 / 263 130 / 184 Step 1 Step 3 NHCBZ Step 4 Step 5 NHCBZ Step 6 Step 7 Step 9 Step 10 Step 11 Intermediate A

[00208] As described in Example 2, A deA 0H(A-COOH) is a heterogeneous compound. (Petition 870250091144, dated 06 / 10 / 2025, p. 139 / 263) 131 / 184 optionally replaced 5 to 6 members, as defined in Formula (A) or Formula (I). In some embodiments, A 0H(A-COOH) is represented by: the HONo, and HO N~n. In some forms, A of Aoh, is represented by A of Formula (A) or the Formula (I). In some embodiments, A of A 0H, is selected from: (CR'R'')m (3- to 10-membered heterocycle), -(CR'R'')m (C3-10 carbocycle), -O(CR'R'')m (3- to 10-membered heterocycle) and -O-(CR'R'')m (C3-10 carbocycle), the 3- to 10-membered heterocycle and the C3-10 carbocycle are each optionally replaced by one or more substituents selected independently from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more substituents independently selected. Petition 870250091144, dated 06 / 10 / 2025, pp. 140 / 263 132 / 184 halogen-containing groups, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; each R' is selected from halogen, -OR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, NO2, -CN; and C1-6 alkyl optionally substituted with one or more halogens, -OR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -NO2, -CN; each R'' is selected from halogen, -OR19, -N(R19)2, -C(O)R19, -C(O)N(R19)2, NO2, -CN; and C1-6 alkyl optionally substituted with one or more halogens, -OR19, -N(R19)2, -C(O)R19, -C(O)N(R19)2, -NO2, -CN; R11, R18, and R19 are each independently selected in each occurrence of: hydrogen; C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; in is selected from 0 and 1

[00209] As described in Example 2, B is an optionally C3-10 carbocycle. Petition 870250091144, dated 06 / 10 / 2025, page 141 / 263 133 / 184 are replaced as defined in Formula (A) or (I). In some forms, AWAZVW WVVWUW í Õu Q B is represented by I, f, eff. In some embodiments, B is represented by B of Formula (A) or Formula (I). In some embodiments, B is selected from -C(H)(R5)2 and C3-10 carbocycle, where each C3-10 carbocycle is optionally replaced with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, N(R12)S(O)2R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN; C1-10 alkyl and C3-10 carbocycle, any of which is optionally substituted with one or more independently selected halogen substituents, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN, C3-10 carbocycle and heterocycle of 3 to 10 members; wherein the C3-10 carbocycle and heterocycle of 3 to 10 members are each optionally substituted with one or more substituents selected from: halogen, -OR12, -N(R12)2, -C(O)R12, C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -NO2, =O, =N(R12), and -CN; and each R5 is independently selected in each occurrence of (i), (ii), and (iii): (i) halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, - N(R13)C(O)R13, -N(R13)S(O)2R13,-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13,-NO2, -CN; (ii) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, Petition 870250091144, dated 06 / 10 / 2025, page 142 / 263 134 / 184 OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13,-NO2, =O, =S, =N(R13), -CN; and (iii) C3-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, NO2, =O, =S, =N(R13), -CN; and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​S(O)2R13, -NO2, =O, =S, =N(R13), and -CN; R12 and R13 are, each independently, selected in each occurrence of: hydrogen; C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN. Example 3: Summary of Intermediates 1 and 2 Petition 870250091144, dated 06 / 10 / 2025, pp. 143 / 263 135 / 184 SFC separation Intermediate 1 Intermediate 2 Petition 870250091144, dated 06 / 10 / 2025, pp. 144 / 263 136 / 184

[00210] A solution of methyl 4,6-dichloropyridazine-3-carboxylate (60.0 g, 290 mmol, 1.00 eq.) in dioxane (1000 mL) was added to diphenylmethanimine (52.5 g, 290 mmol, 48.6 mL, 1.00 eq.), CS2CO3 (189 g, 580 mmol, 2.00 eq.), Pd2(dba)3 (13.3 g, 14.5 mmol, 0.0500 eq.) and Xantfos (16.8 g, 29.0 mmol, 0.100 eq.) at room temperature. The reaction mixture was stirred at 90 °C for 16 h. The reaction mixture was diluted with DCM (1000 mL), then filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, PE: EtOAc = 5:1) to give methyl 4-chloro-6-((diphenylmethylene)amino)pyridazine-3-carboxylate (53.4 g, 152 mmol, 52.4% yield) as a yellow oil. LCMS [M+H]+ = 352.1 m / z.

[00211] To a solution of methyl 4-chloro-6-((diphenylmethylene)amino)pyridazine-3-carboxylate (53.4 g, 152 mmol, 1.00 eq.) in HCl / dioxane (4 M, 534 mL, 14.1 eq.) was added H2O (125 mL) at 0°C. The reaction mixture was stirred at 25°C for 12 h. The reaction mixture was treated with saturated aqueous NaHCO3 to pH around 8, then diluted with EtOAc (200 mL) and filtered. The filtrate was extracted with EtOAc (500 mL x 3). The filtered mass was stirred as a suspension with 150 mL of EtOAc:MeOH (10:1) and filtered. The combined organic layers were dried over anhydrous Na2SO4 and filtered. Petition 870250091144, dated 06 / 10 / 2025, pages 145 / 263 137 / 184 and concentrated under reduced pressure to provide a residue. The residue was purified by column chromatography (SiO2, PE: EtOAc 1:1) to provide methyl 6-amino-4-chloropyridazine-3-carboxylate (13.3 g, 70.9 mmol, yield of 46.7%) as a white solid. LCMS [M+ H]+= 188.0 m / z.

[00212] To a solution of methyl 6-amino-4-chloropyridazine-3-carboxylate (1.20 g, 6.40 mmol, 1.00 eq.) in THF (10.0 mL) was added benzyl (S)-(3-bromo-1(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate (2.07 g, 5.12 mmol, 0.800 eq.), B(OMe)3 (3.32 g, 32.0 mmol, 3.61 mL, 5.00 eq.) and DIEA (4.13 g, 32.0 mmol, 5.57 mL, 5.00 eq.) at room temperature. The reaction mixture was stirred at 70 °C for 2 h. The reaction mixture was diluted with EtOAc (50.0 mL), filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, PE: EtOAc, 3:1) to give (S)-2-((((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazine-6-carboxylate methyl (1.40 g, 2.84 mmol, yield of 44.4%) as a yellow oil. LCMS [M+H]+ = 493.2 m / z.

[00213] To a solution of (S)-2-((((benzyloxy)carbonyl)amino)(4,4-Petition 870250091144, dated 06 / 10 / 2025, page 146 / 263 138 / 184 difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazine-6-carboxylate methyl (1.40 g, 2.84 mmol, 1.00 eq.) in MeOH (20.0 mL) was added CaCl2 (946 mg, 8.52 mmol, 3.00 eq.) and NaBH4 (537 mg, 14.2 mmol, 5.00 eq.) at 0°C. The reaction mixture was stirred at room temperature for 50 min. The reaction mixture was quenched with 30.0 mL of saturated aqueous NH4Cl, then concentrated under reduced pressure to remove MeOH. The aqueous layer was extracted with 90.0 mL of EtOAc (30.0 mL x 3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give crude benzyl (S)-((7-chloro-6-(hydroxymethyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)carbamate (1.18 g, 2.54 mmol, 89.4% yield) as a yellow foam, which was used directly in the next step. LCMS [M+H]+ = 465.2 m / z.

[00214] To a solution of (S)-((7-chloro-6-(hydroxymethyl)imidazo[1,2b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)benzyl carbamate (1.18 g, 2.54 mmol, 1.00 eq.) in DCM (10.0 mL) was added SOCl2 (906 mg, 7.61 mmol, 553 μL, 3.00 eq.) at room temperature. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure to give crude benzyl (S)-((7-chloro-6-(chloromethyl)imidazo[1,2b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)carbamate (1.13 g, 2.34 mmol, 92.1% yield) as a yellow foam, which was used directly in the next step. LCMS [M+ H]+ = 483.1 m / z. Petition 870250091144, dated 06 / 10 / 2025, pp. 147 / 263 139 / 184

[00215] To a solution of (5R)-2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate of 1-(tert-butyl)3-methyl (626 mg, 1.92 mmol, 1.00 eq.) in THF (20.0 mL) was added CS2CO3 (2.51 g, 7.70 mmol, 4.00 eq.) at room temperature. The reaction mixture was stirred at room temperature for 1 h. To the reaction mixture was added (S)-((7-chloro-6-(chloromethyl)imidazo[1,2b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)benzyl carbamate (930 mg, 1.92 mmol, 1.00 eq.) at room temperature. The reaction mixture was stirred at 70 °C for 11 h. The reaction mixture was diluted with EtOAc (100 mL), filtered, and concentrated under reduced pressure to provide a residue.The residue was purified by column chromatography (SiO2, PE:EtOAc, 1:1) to give (5R)-3-((2-((S)-(((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate of 1-(tert-butyl)3-methyl (507 mg, 657 μmol, 34.1% yield) as a colorless gum. LCMS [M+ H]+= 772.4 m / z. Petition 870250091144, dated 06 / 10 / 2025, pp. 148 / 263 140 / 184

[00216] (5R)-3-((2-((S)-(((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5(trifluoromethyl)piperidine-1,3-dicarboxylate of 1-(tert-butyl)3-methyl (500 mg, 648 pmol, 1.00 eq.) was dissolved in HCl (12 M, 5.00 mL, 92.7 eq.) and AcOH (524 mg, 8.73 mmol, 0.500 mL, 13.5 eq.) at room temperature. The reaction mixture was stirred at 60°C for 1 h. The reaction mixture was treated with saturated aqueous NaHCO3 until the pH was around 8, then extracted with EtOAc (50.0 mL x 3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give crude methyl (5R)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (200 mg, 372 pmol, 57.4% yield) as a yellow gum, which was used directly in the next step. LCMS [M+ H]+ = 538.2 m / z.

[00217] To a solution of (5R)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5(trifluoromethyl)piperidine-3-carboxylate methyl (200 mg, 372 pmol, 1.00 eq.) in pyridine (2.00 mL) was added 1-ethyl-1H-pyrazole-5-carboxylic acid (52.1 mg, 372 pmol, 1.00 eq.) and EDCI (143 mg, 744 pmol, 2.00 eq.) at room temperature. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was treated with 1 M HCl until the pH was around 7, then extracted with EtOAc (10.0 mL x 3). The organic layers Petition 870250091144, dated 06 / 10 / 2025, pp. 149 / 263 141 / 184 combined samples were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide a residue. The residue was purified by preparative TLC (SiO2, PE: EtOAc, 1:1) to provide (5R)-3-((7-chloro2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazol-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5(trifluoromethyl)piperidine-3-carboxylate methyl (150 mg, 227 μmol, 61.1% yield) as a white foam. LCMS [M+ H]+ = 660.1 m / z.

[00218] To a solution of (5R)-3-((7-chloro-2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazol-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5(trifluoromethyl)piperidine-3-carboxylate methyl (150 mg, 227 μmol, 1.00 eq.) in THF (2.00 mL) and H2O (2.00 mL) was added LiOH-HaO (19.1 mg, 454 μmol, 2.00 eq.) at room temperature. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was treated with 1 M HCl until the pH was around 4, then extracted with EtOAc (5.00 mL x 3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give crude (5R)-3((7-chloro-2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazol-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5(trifluoromethyl)piperidine-3-carboxylic acid (130 mg, 201 pmol, 88.6% yield) as a white solid, which was used directly in the next step. LCMS [M+ H]+ = 646.1 m / z. Petition 870250091144, dated 06 / 10 / 2025, pages 150 / 263 142 / 184 Intermediate 1 Intermediate 2

[00219] To a solution of (5R)-3-((7-chloro-2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazol-5-carboxamido)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)2-oxo-5-(trifluoromethyl)piperidine-3-carboxylic acid (130 mg, 201 μmol, 1.00 eq.) in DMSO (1.00 mL) was added NaCl (11.8 mg, 201 μmol, 1.00 eq.) at 20°C. The reaction mixture was stirred at 110°C for 30 min. The reaction mixture was diluted with H2O (10.0 mL) and extracted with EtOAc (10.0 mL x 3). The organic layers were washed with brine (10.0 mL x 2) and H2O (10.0 mL x 2), dried over anhydrous Na2SO4 solution, filtered, and concentrated under reduced pressure to provide a residue.The residue was purified by preparative HPLC (condition FA, column: Phenomenex luna C18 150 * 25 mm * 10 pm; phase: [water (formic acid) - ACN]; B%: 42-72%) to give N-((1S)-(7chloro-6-(((5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (68.0 mg, 113 pmol, yield of 56.1%) as a white solid with dr = 64:36. The residue was purified by prep-SFC (column: REGIS (R, R) WHELK - O1 (250 mm x 25 mm, 10 µm); mobile phase: [0.1% NH3H2O ​​EtOH]; B%: 50%) to provide intermediate 1 (LCMS [M+H]+= 602.1 m / z.) as the first single stereoisomer eluent and intermediate 2 (LCMS [M+H]+= 602.2 m / z.) as the second single stereoisomer eluent. Example 4: Preparation for Intermediate Levels 3 and 4 Intermediate 3 Preparation Petition 870250091144, dated 06 / 10 / 2025, pp. 151 / 263 143 / 184

[00220] N-((1S)-(7-chloro-6-(((5R)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide was synthesized according to General Procedure 1, employing (5R)-3-((6-amino-4-chloropyridazin-3-yl)methyl)-5-methylpiperidin-2-one and (S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)benzyl carbamate, General Procedure 2, employing ((1S)-(7-chloro-6-(((5R)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)benzyl carbamate and General Procedure 4, employing (5R)-3((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-5-methylpiperidin-2-one and 1-ethyl-1H-pyrazol-5-carboxylic acid. Intermediate 4 Preparation

[00221] N-((1S)-(7-chloro-6-(((5S)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide was synthesized according to General Procedure 1, employing (5S)-3-((6-amino-4-chloropyridazin-3-yl)methyl)-5-methylpiperidin-2-one and (S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)benzyl carbamate, Petition 870250091144, dated 06 / 10 / 2025, pages 152 / 263 144 / 184 General Procedure 2, employing ((1S)-(7-chloro-6-(((5S)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)benzyl carbamate and General Procedure 4, employing (5S)-3((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-5-methylpiperidin-2-one and 1-ethyl-1H-pyrazol-5-carboxylic acid. Example 5: Synthesis of Compound 21

[00222] A mixture of intermediate 1 (80.0 mg, 133 μmol, 1.00 eq.), 2(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (558 mg, 2.66 mmol, 20 eq.), K3PO4 (84.6 mg, 399 μmol, 3.00 eq.) and Pd(dtbpf)Cl2 (8.66 mg, 13.29 μmol, 0.1 eq.) in dioxane (2.00 mL) and H2O (0.5 mL) was degassed and purged with N2 three times, and then the mixture was stirred at 90°C for 1 h under an N2 atmosphere. The reaction mixture was diluted with 50.0 mL of H2O and extracted with EtOAc (50.0 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a residue, which was purified by preparative TLC (SiO2, DCM:MeOH = 10:1) to provide N-((S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-pyran-4-yl)-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide (60.0 mg, 92.4 μmol, yield of 69.5%) as a yellow solid. LCMS [M+ H]+= 650.4 m / z. Petition 870250091144, dated 06 / 10 / 2025, pp. 153 / 263 145 / 184

[00223] For a solution of N-((S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2Hpyran-4-yl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2 b)pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (30.0 mg, 46.2 μmol, 1.00 eq.) in THF (5.00 mL) was added to Pd / C (20.0 mg, 18.8 pmol, 10% purity) under N2. The suspension was degassed under vacuum and purged with H2 several times. The reaction mixture was stirred under H2 (15 psi) at 15°C for 24 h. The reaction mixture was filtered. The filtrate was diluted with MeOH (50.0 mL) before being filtered again. The filtrate was concentrated under reduced pressure to provide a residue, which was purified by preparative TLC (SiO2, DCM: MeOH = 10:1) to provide N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)-7-(tetrahydro-2H-pyran-4yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (7.68 mg, 11.04 μmol, yield of 23.91%, purity of 93.7%) as a white solid. LCMS [M+ H]+= 652.5 m / z. Example 6: Synthesis of Compound 33 N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5 Petition 870250091144, dated 06 / 10 / 2025, pp. 154 / 263 146 / 184 (trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (50.0 mg, 83.0 μmol, 1.00 eq.) and (R)-2-methylmorpholine (84.0 mg, 830 μmol, 10.0 eq.) in dioxane (1.00 mL) were added to CS2CO3 (81.1 mg, 249 pmol, 3.00 eq.) and PEPPSI-Pd-iHept (8.08 mg, 8.31 μmol, 0.100 eq.) under N2. The reaction mixture was stirred at 90 °C for 12 h under N2. The reaction mixture was diluted with H2O (10.0 mL) and extracted with EtOAc (10.0 mL x 3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a residue.The residue was purified by preparative HPLC (column: Waters Xbridge 150 x 25 mm x 5 µm; mobile phase: [water (ammonium hydroxide v / v) - ACN]; gradient: 34% - 64%) to give N-((S)-(4,4-difluorocyclohexyl)(7-((R)-2-methylmorpholino)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (15.2 mg, 22.3 pmol, yield 26.9%, purity 98.1%) as a white solid. LCMS [M+H]+ = 667.4 m / z. Example 7: Preparation of Compound 111 ^bf3k —N -------► Pd(t-Bu3P)2, DIEA, dioxane, H2O

[00225] A solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (100 mg, 166 pmol, 1.00 eq.), potassium ((dimethylamino)methyl)trifluoroborate (prepared according to general procedure 5, 137 mg, 831 pmol, 5.00 eq.), Pd(t-Bu3P)2 (25.5 mg, 49.8 pmol, 0.30 eq.) and DIEA (64.4 mg, 498 pmol, 86.8 pL, 3.00 eq.) in dioxane Petition 870250091144, dated 06 / 10 / 2025, pages 155 / 263 147 / 184 (2.00 mL) was added to water (0.40 mL). The reaction mixture was heated to °C for 2 h in a sealed tube under microwave irradiation. The reaction mixture was filtered with MeOH (10.0 mL) and the filtrate was concentrated under reduced pressure to provide a residue that was purified by Prep-HPLC (column: Phenomenex luna C18 150 mm x 25 mm, 10 µm; mobile phase: [water (FA) - ACN]; gradient: 18% - 38% B over 10 min) and then purified by Prep-SFC (column: DAICEL CHIRALPAK AS (250 mm x 30 mm, 10 µm); Mobile phase: [CO2 - EtOH (0.1% NH3H2O)]; B%: 25%, isocratic elution mode) to provide N-((S)-(4,4-difluorocyclohexyl)(7-((dimethylamino)methyl)-6(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (42.36 mg, 67.8 μmol, production of 40.8%, 99.9% purity) as a white solid. LCMS [M+H]+ = 625.3 m / z. Example 8: Preparation of Compound 108 ^bf3k Pd(t-Bu3P)2, DIEA, dioxane, H2O

[00226] A solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (80.0 mg, 133 pmol, 1.00 eq.), potassium ((morpholino)methyl)trifluoroborate (prepared according to the general procedure 5, 138 mg, 664 μmol, 5.00 eq.), Pd(t-Bu3P)2 (20.4 mg, 39.9 pmol, 0.300 eq.) and DIEA (51.5 mg, 399 μmol, 69.4 pL, 3.00 eq.) in dioxane (2.00 mL) was added to water (0.40 mL). The reaction mixture was heated to 90°C for 2 h in a sealed tube under microwave irradiation. The mixture Petition 870250091144, dated 06 / 10 / 2025, pp. 156 / 263 148 / 184 of the reaction was filtered with MeOH (10.0 mL) and the filtrate was concentrated under reduced pressure to provide a residue that was purified by Prep-HPLC (column: Phenomenex luna C18 150 mm x 25 mm, 10 µm; mobile phase: [water (FA) - ACN]; gradient: 20% - 40% B over 10 min) to provide N-((S)(4,4-difluorocyclohexyl)(7-(morpholinomethyl)-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide (42.58 mg, 63.2 μmol, yield of 47.5%, purity of 98.9%) as a white solid. LCMS [M+ H]+ = 667.3 m / z. Example 9: Preparation of Compound 107

[00227] A solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (60.0 mg, 99.6 μmol, 1.00 eq.), potassium (piperidin-1-ylmethyl)trifluoroborate (prepared according to the general procedure 5, 102 mg, 498 pmol, 5.00 eq.), Pd(t-Bu3P)2 (15.2 mg, 29.90 μmol, 0.300 eq.) and DIEA (38.6 mg, 299 pmol, 52.0 pL) (3.00 eq.) in dioxane (2.00 mL) and water (0.40 mL) was added. The reaction mixture was heated to 90 °C for 2 h in a sealed tube under microwave irradiation. The reaction was cooled to room temperature, diluted with water, and an extraction was performed with ethyl acetate.The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to provide a residue that was purified by Prep-HPLC (column: Phenomenex luna C18 150 mm x 25 mm, 10 µm; mobile phase: [water (FA)] Petition 870250091144, dated 06 / 10 / 2025, p. 157 / 263. 149 / 184 ACN]; gradient: 15% to 45% B over 10 min) to give N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)-7(piperidin-1-ylmethyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (25.8 mg, 38.77 μmol, 38.90% yield, 99.89% purity) as a white solid. LCMS [M+H]+ = 665.4 m / z. Example 10: Preparation of Compound 106

[00228] A solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (100 mg, 166 μmol, 1.00 eq.), potassium (pyrrolidin-1-ylmethyl)trifluoroborate (prepared according to the general procedure 5, 159 mg, 831 μmol, 5.00 eq.), Pd(t-BuaP)2 (25.5 mg, 49.8 μmol, 0.300 eq.) and DIEA (64.4 mg, 498 μmol, 86.8 μL, 3.00 eq.) in dioxane (2.00 mL) was added to water (0.40 mL). The reaction mixture was heated to 90 °C for 2 h in a sealed tube under microwave irradiation.The reaction mixture was filtered with MeOH (10.0 mL) and the filtrate was concentrated under reduced pressure to provide a residue that was purified by Prep-HPLC (column: Phenomenex luna C18 150 mm x 25 mm, 10 µm; mobile phase: [water (FA) - ACN]; gradient: 23% - 41% B over 9 min) and then purified by Prep-SFC (column: REGIS (S, S) WHELK-O1 (250 mm x 25 mm, 10 µm); mobile phase: [CO2 - ACN / MeOH (0.1% NH3H2O)]; B%: 40%, isocratic elution mode) to provide N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R) )-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)-7-(pyrrolidin-1-ylmethyl)imidazo[1,2-b]pyridazin-2. Petition 870250091144, dated 06 / 10 / 2025, pages 158 / 263 150 / 184 yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (46.21 mg, 70.7 μmol, yield of 42.6%, purity of 99.6%) as a white solid. LCMS [M+H]+ = 651.2 m / z. Example 11: Preparation of Compound 115

[00229] N-((S )-(4,4-difluorocyclohexyl)(6-(((3R, 5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)-7-(((2,2,2-trifluoroethyl)amino)methyl)imidazo[1,2b]pyridazin-2-yl)methyl)-1-ethyl- 1H-pyrazole-5-carboxamide was synthesized following General Procedure 6 with N-((S )-(4,4-difluorocyclohexyl)(7-formyl-6-((( 3R, 5R)2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1ethyl- 1H-pyrazole-5-carboxamide (100 mg, 168 pmol, 1.00 eq.), 2,2,2-trifluoroethan-1-amine (166 mg, 1.68 mmol, 132 μL, 10.0 eq.) and was purified by Prep-HPLC (column: Waters Xbridge 150 mm x 25 mm, 5 μm; mobile phase: [water (ammonium hydroxide v / v)-ACN]; gradient: 39% - 69% B over 9 min) to provide N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)-7-(((2,2,2-trifluoroethyl)amino)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (28.39 mg, 40.7 μmol, 24.3% yield, 97.4% purity) as a white solid.LCMS [M+ H]+ = 679.3 m / z. Example 12: Preparation of Compound 109 Petition 870250091144, dated 06 / 10 / 2025, pp. 159 / 263 151 / 184

[00230] N-((S )-(7-((3,3-difluoroazetidin-1-yl)methyl)-6-(((3R, 5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl- 1H-pyrazole-5-carboxamide was synthesized following General Procedure 6 with N-((S)-(4,4-difluorocyclohexyl)(7-formyl-6-(((3R, 5R)-2oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl1H -pyrazole-5-carboxamide (70.0 mg, 118 μmol, 1.00 eq.), 3,3-difluoroazetidine (152 mg, 1.18 mmol, 10.0 eq., HCl salt) and was purified by preparative HPLC (column: Waters Xbridge 150 mm x 25 mm, 5 µm; mobile phase: [water (ammonium hydroxide v / v)-ACN]; gradient: 38% - 68% B over 9 min) to provide N-((S)-(7-((3,3-difluoroazetidin-1-yl)methyl)-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (39.3 mg, 57.7 μmol, yield of 49.1%, purity of 98.8%) as a whitish solid.LCMS [M+H]+ = 673.3 m / z. Example 13: Preparation of Compound 105 Petition 870250091144, dated 06 / 10 / 2025, pp. 160 / 263 152 / 184

[00231] N-((S )-(4,4-difluorocyclohexyl)(7-((3,3-difluoropyrrolidin-1-yl)methyl)-6(((3R, 5R )-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2yl)methyl)-1-ethyl- 1H-pyrazole-5-carboxamide was synthesized following General Procedure 6 with N-((S)-(4,4-difluorocyclohexyl)(7-formyl-6-(((3R, 5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl- 1Hpyrazole-5-carboxamide (70.0 mg, 118 μmol, 1.00 eq.), 3,3-difluoropyrrolidine (126 mg, 1.18 mmol, 10.0 eq., HCl salt) and was purified by Prep-HPLC (column: Waters Xbridge 150 mm x 25 mm, 5 µm; mobile phase: [water (ammonium hydroxide v / v)-ACN]; gradient: 32% - 62% B over 9 min) to provide N-((S)-(4,4-difluorocyclohexyl)(7-((3,3-difluoropyrrolidin-1-yl)methyl)-6-(((3R, 5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)1-ethyl-1H-pyrazol-5-carboxamide (44.8 mg, 65.2 μmol, 55.5% yield, 99.9% purity) as a brown solid. LCMS [M+H]+ = 687.4 m / z. Example 14: Preparation of Compound 112

[00232] N-((S )-(4,4-difluorocyclohexyl)(7-((methylamino)methyl)-6-(((3R, 5R)-2oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl1H-pyrazol-5-carboxamide was synthesized following the General Procedure 6 with N -((S )-(4,4-difluorocyclohexyl)(7-formyl-6-((( 3R, 5R )-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H pyrazol-5-carboxamide (70.0 mg, 118 μmol, 1.00 eq.), methanamine (79.4 mg, 1.18 mmol, 10.0 eq., HCl salt) and was purified by preparative HPLC (column: Waters Xbridge 150 mm x 25 mm, 5 µm; mobile phase: [water (ammonium hydroxide) Petition 870250091144, dated 06 / 10 / 2025, pp. 161 / 263 153 / 184 nia v / v)-ACN]; gradient: 42% - 72% B in 9 min) to provide N-((S)-(4,4-difluorocyclohexyl)(7-((methylamino)methyl)-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (37.17 mg, 56.4 μmol, yield of 48.0%, purity of 92.6%) as a whitish solid. LCMS [M+H]+ = 611.3 m / z. Example 15: Preparation of Compound 116

[00233] N-((S)-(4,4-difluorocyclohexyl)(7-((methyl(2,2,2-trifluoroethyl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide was synthesized following General Procedure 6 with N-((S)-(4,4-difluorocyclohexyl)(7-formyl-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (70.0 mg, 118 pmol, 1.00 eq.), 2,2,2-trifluoro-N-methylethan-1-amine (176 mg, 1.18 mmol, 10.0 eq., HCl salt) and was purified by preparative HPLC (column: Waters Xbridge 150 mm x 25 mm, 5 µm; mobile phase: [water (ammonium hydroxide v / v)-ACN]; gradient: 43% - 73% B over 9 min) to give N ((S)-(4,4-difluorocyclohexyl)(7-((methyl(2,2,2-trifluoroethyl)amino)methyl)-6(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (42.15 mg, 59.7 μmol, yield 50.8%, purity 98.1%) as a white solid. LCMS [M+H]+ = 693.3 m / z. Example 16: Preparation of Compound 113. Petition 870250091144, dated 06 / 10 / 2025, pp. 162 / 263 154 / 184 The synthesized following General Procedure 6 with N-((S)-(4,4-difluorocyclohexyl)(7-formyl-6-(((3R, 5R)-2oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl1H-pyrazol-5-carboxamide (80.0 mg, 134 μmol, 1.00 eq.), N-methylcyclopropanamine (145 mg, 1.34 mmol, 10.0 eq., HCl salt) was purified by PrepHPLC (column: Waters Xbridge 150 mm x 25 mm, 5 µm; mobile phase: [water (ammonium hydroxide v / v)-ACN]; gradient: 42% - 72% B over 9 min) to give N-((S)-(7-((cyclopropyl(methyl)amino)methyl)-6-(((3R,5R))-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (45.53 mg, 68.6 pmol, 51.1% yield, 98.0% purity) as a whitish solid.LCMS [M+H]+ = 651.3 m / z. Example 17: Preparation of Compound 114

[00235] N-((S)-(4,4-difluorocyclohexyl)(7-((methyl(oxetan-3-yl)amino)methyl)-6Petition 870250091144, of 10 / 06 / 2025, page 163 / 263 155 / 184 (((3R, 5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide was synthesized following General Procedure 6 with N-((S)-(4,4-difluorocyclohexyl)(7-formyl-6-(((3R, 5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (80.0 mg, 134 μmol, 1.00 eq.), N-methyloxetan-3-amine (117 mg, 1.34 mmol, 10.0 eq.) and was purified by Prep-HPLC (column: Waters Xbridge 150 mm x 25 mm, 5 µm; mobile phase: [water (ammonium hydroxide v / v)ACN]; gradient: 33% - 63% B over 9 min) to give N-((S)-(4,4-difluorocyclohexyl)(7-((methyl(oxetan-3-yl)amino)methyl)-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide (41.97 mg, 62.0 μmol, 46.1% yield, 98.4% purity) as a white solid. LCMS [M+H]+ = 667.3 m / z. Example 18: Preparation of Compound 117

[00236] N-((S )-(7-((cyclopropylamino)methyl)-6-(((3R, 5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide was synthesized following General Procedure 6 with N-((S)-(4,4-difluorocyclohexyl)(7-formyl-6-(((3R, 5R)-2oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl1H-pyrazol-5-carboxamide (100 mg, 168 pmol, 1.00 eq.), cyclopropylamine (95.9 mg, 1.68 mmol, 116 μL, 10.0 eq.) and was purified by preparative TLC (SiO2, petroleum ether: ethyl acetate = 0:1, Rf = 0.30) to give N-((S)(7-((cyclopropylamino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3 Petition 870250091144, dated 06 / 10 / 2025, pages 164 / 263 156 / 184 yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide (28.0 mg, 44.0 μmol, yield of 26.2%) as a white solid. LCMS [M+H]+ = 637.3 m / z.

[00237] To a solution of N-((S)-(7-((cyclopropylamino)methyl)-6-(((3R,5R)-2oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (28.0 mg, 44.0 μmol, 1.00 eq.) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (102 mg, 440 μmol, 10.0 eq.) in DMF (0.500 mL) was added DIEA (34.1 mg, 264 μmol, 46.0 μL, 6.00 eq.). The reaction mixture was stirred at 100°C for 12 hours.The reaction mixture was cooled to room temperature and filtered with MeOH (10.0 mL). The filtrate was concentrated under reduced pressure to provide a residue that was purified by Prep-HPLC (column: Waters Xbridge 150 mm x 25 mm, 10 µm; mobile phase: [water (ammonium hydroxide v / v) - ACN]; gradient: 47% 77% B over 9 min) to provide N-((S)-(7-((cyclopropyl(2,2,2-trifluoroethyl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (10.74 mg, 14.2 pmol, 32.4% yield, 95.3% purity) as a brown solid. LCMS [M+H]+ = 719.3 m / z. Example 19: Preparation of Compound 110 Petition 870250091144, dated 06 / 10 / 2025, pages 165 / 263 157 / 184 2) 2M HCl3)2°Al2' dioxane,MW

[00238] To a solution of N-((S )-(7-chloro-6-((( 3R,5R )-2-oxo-5 (trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl- 1H-pyrazol-5-carboxamide (0.28 g, 465 μmol, 1.00 eq.) in dioxane (1.00 mL) was added tributyl(1-ethoxyvinyl)estanane (335 mg, 930 μmol, 314 μL, 2.00 eq.) followed by Pd(PPh3)2Cl2 (32.6 mg, 46.5 μmol, 0.100 eq.). The reaction mixture was heated to 110°C for 6 h under microwave irradiation. The reaction mixture was quenched by the addition of a saturated aqueous solution of KF (10.0 mL) at 20°C. The reaction mixture was diluted with 2 M HCl (20.0 mL) and stirred again at 20°C for 2 h. The reaction mixture was then adjusted to pH = 7 with a saturated aqueous solution of NaHCl, filtered, and extracted with ethyl acetate (3 x 30.0 mL).The combined organic layers were washed with a saturated aqueous solution of NaCl (3 x 30.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide a residue that was purified by Prep-TLC (SiO2, Dichloromethane: Methanol = 10:1) to provide N-((S)-(7-acetyl6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (170 mg, 278 pmol, yield of 59.9%) as a white solid. Petition 870250091144, dated 06 / 10 / 2025, pages 166 / 263 158 / 184

[00239] To a solution of N-((S)-(7-acetyl-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (160 mg, 262 μmol, 1.00 eq.) in MeOH (2.00 mL) was added sodium borohydride (19.8 mg, 524 pmol, 2.00 eq.) at 0 °C under N2. The reaction mixture was stirred at 25 °C for 1 h. The reaction mixture was quenched by the addition of a saturated aqueous solution of NH4Cl (10 mL) at 0°C and then diluted with water (30.0 mL). An extraction was performed with ethyl acetate (3 x 30.0 mL) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give N-((1S)-(4,4-difluorocyclohexyl)(7-(1-hydroxyethyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (160 mg, 261 pmol, 99.6% yield) as a white solid. LCMS [M+H]+ = 612.4 m / z.

[00240] A solution of N-((1S)-(4,4-difluorocyclohexyl)(7-(1-hydroxyethyl)6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2 Petition 870250091144, dated 06 / 10 / 2025, pp. 167 / 263 159 / 184 yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (80.0 mg, 130 μmol, 1.00 eq.) in DCM (1.00 mL) was added thionyl chloride (46.6 mg, 392 pmol, 28.5 μL, 3.00 eq.) at 0°C. The reaction mixture was stirred at 25°C for 0.5 h. The reaction mixture was concentrated under reduced pressure to provide a residue which was purified by Prep-TLC (SiO2, Dichloromethane: Methanol = 10:1) to give N-((1S)-(7-(1-chloroethyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide (70.0 mg, 111 pmol, yield of 84.9%) as a white solid. LCMS [M+H]+ = 630.2 m / z.

[00241] To a solution of N-((1S)-(7-(1-chloroethyl)-6-(((3R, 5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (70.0 mg, 111 pmol, 1.00 eq.) and 2,2,2-trifluoroethan-1-amine (220 mg, 2.22 mmol, 174 pL, 20.0 eq.) in DMF (1.00 mL) was added DIEA (43.0 mg, 333 pmol, 58.0 pL, 3.00 eq.). The reaction mixture was stirred at 70°C for 10 h. The reaction mixture was diluted with water (30.0 mL) and extracted with ethyl acetate (3 x 30.0 mL).The combined organic layers were washed with brine (2 x 30.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide a residue that was purified by preparative TLC (SiO2, petroleum ether: ethyl acetate = 0:1) to provide N-((1S)-(4,4-difluorocyclohexyl)(6-(((3R,5R))-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)-7-(1-((2,2,2-trifluoroethyl)amino)ethyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5. Petition 870250091144, dated 06 / 10 / 2025, pp. 168 / 263 160 / 184 carboxamide (45.0 mg, 64.9 μmol, yield of 58.4%) as a white solid. LCMS [M+H]+ = 693.2 m / z.

[00242] To a solution of N-((1S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)-7-(1-((2,2,2-trifluoroethyl)amino)ethyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (45.0 mg, 64.9 μmol, 1.00 eq.), formaldehyde (527 mg, 6.50 mmol, 483 pL, 37.0% purity, 100 eq.), AcOH (3.90 mg, 64.9 pmol, 3.72 pL, 1.00 eq.) in MeOH (1.00 mL) was added NaBHaCN (12.2 mg, 194 pmol, 3.00 eq.). The reaction mixture was stirred at 25°C for 1 h.The reaction mixture was filtered to provide a residue which was purified by preparative HPLC (condition FA, column: Phenomenex luna C18 150 mm x 25 mm, 10 µm; mobile phase: [water (FA)-ACN]; gradient: 53% to 73% B over 10 min) to provide N-((1S)-(4,4-difluorocyclohexyl)(7-(1-(methyl(2,2,2-trifluoroethyl)amino)ethyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (40.0 mg, 56.6 pmol, yield of 87.1%) as a white solid. LCMS [M+ H]+ = 707.3 m / z.

[00243] Compound 110 was isolated as the second eluent single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AD (250 mm x 30 mm, 10 µm); mobile phase: [CO2-EtOH (0.1% NH3H2O)]; B%: 20%, isocratic elution mode); (10.21 mg, 14.3 pmol, 25.4% yield, 99.5% purity) and was obtained as a white solid. LCMS [M+ H]+= 707.3 m / z. Petition 870250091144, dated 06 / 10 / 2025, pp. 169 / 263 161 / 184 Example 20: Preparation of Compound 104 PEPPSI-Pd-iHept, Cs2CO3dioxane

[00244] To a solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (100 mg, 166 μmol, 1.00 eq.) and (S)-octahydropyrazino[2,1-c][1,4]oxazine (472 mg, 3.32 mmol, 20.0 eq.) in dioxane (2.00 mL) was added 1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-2H-imidazol-1-io-2-ide;3-chlorpyridine;dichloropalladium (1.62 mg, 1.66 pmol, 0.01 eq.) and CS2CO3 (162 mg, 498 pmol, 3.00 eq.). The reaction mixture was stirred at 100°C for 6 h under N2.The reaction mixture was diluted with water (15.0 mL) and extracted with ethyl acetate (3 x 15.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide a residue that was purified by Prep-HPLC (column: Phenomenex luna C18 150 mm x 25 mm, 10 µm; mobile phase: [water (FA) - ACN]; gradient: 25% - 45% B over 10 min) and subsequently purified by Prep-SFC (column: REGIS (S, S) WHELK-O1 (250 mm x 25 mm, 10 µm); mobile phase: [CO2-i-PrOH / ACN]; B%: 50%, isocratic elution mode) to provide N-((S)-(4,4-difluorocyclohexyl)(7-(( S )-hexa-hydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl)-6-(((3R,5R)-2-oxo5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide (20.49 mg, 28.7 pmol, yield 17.2%, purity 99.2%) as a white solid. LCMS [M+H]+= 708.3 m / z. Example 21: Preparation of Compound 99 Petition 870250091144, dated 06 / 10 / 2025, pp. 170 / 263 162 / 184 HN—v HN^ / CF3 0=^ / CF3 \=N / --\ \=N ci—ά N-^ —Xj-N Boc-N N—ά N-^ ^NN HL ') Boc-N NH ]l H 7 A NN—► N PEPPSI-Pd-iHept, Cs2CO3___J dioxane FFFF

[00245] To a solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (250 mg, 415 μmol, 1.00 eq.) and tert-butyl piperazine-1-carboxylate (1.55 g, 8.31 mmol, 20.0 eq.) in dioxane (3.00 mL) was added 1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-2-himidazol-1-io-2-ide; 3-chloropyridine; dichloropalladium (4.04 mg, 4.15 μmol, 0.0100 eq.) and Cs2CO3 (405 mg, 1.25 mmol, 3.00 eq.). The reaction mixture was stirred at 100°C for 10 h under N2.The reaction mixture was diluted with water (15.0 mL) and extracted with ethyl acetate (3 x 15.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide a residue that was purified by preparative HPLC (column: Waters Xbridge C18 150 mm x 50 mm, 10 µm; mobile phase: [water (NH4HCO3)-ACN]; gradient: 38% 68% B over 10 min) to provide 4-(2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazol-5-carboxamido)methyl)-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-7-yl)piperazine-1-carboxylate tert-butyl (60 mg, 79.8 μmol, yield of 19.2%) as a white solid. LCMS [M+H]+= 752.4 m / z. Petition 870250091144, dated 06 / 10 / 2025, pp. 171 / 263 163 / 184

[00246] To a solution of 4-(2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1Hpyrazol-5-carboxamido)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3yl)methyl)imidazo[1,2-b]pyridazin-7-yl)piperazine-1-carboxylate tert-butyl (55.0 mg, 73.1 μmol, 1.00 eq.) in DCM (0.500 mL) was added ZnBr2 (82.3 mg, 365 pmol, 18.3 μL, 5.00 eq.). The reaction mixture was stirred at 25°C for 6 h. The reaction mixture was diluted with water (10.0 mL) and the pH was adjusted to 8 with a saturated aqueous solution of NaHCO3, extracted with DCM (15.0 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give N-((S)(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)-7(piperazin-1-yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (45.0 mg, 69.0 μmol, 94.3% yield) as a yellow solid. LCMS [M+H]+ = 652.3 m / z.

[00247] To a solution of N-((S)-(4,4-difluorocyclohexyl)(6-(((3R, 5R)-2oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)-7-(piperazin-1-yl)imidazo[1,2b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (45.0 mg, 69.0 μmol, 1.00 eq.) and 1-bromo-2-methoxyethane (38.3 mg, 276 pmol, 25.9 μL, 4.00 eq.) in DMF (1.00 mL) was added DIEA (44.6 mg, 345 pmol, 60.1 pL, 5.00 eq.). The mixture was stirred at 25°C for 12 h. The reaction mixture was diluted with water (15.0 mL) and extracted with ethyl acetate (3 x 15.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide a residue that was purified by preparative TLC (SiO2, ethyl acetate). Petition 870250091144, dated 06 / 10 / 2025, pp. 172 / 263 164 / 184 la:methanol = 9:1) and subsequently purified by preparative HPLC (column: Phenomenex luna C18 150 mm x 25 mm, 10 μm; mobile phase: [water (FA) ACN]; gradient: 23% - 43% B over 10 min) to give N-((S)-(4,4-difluorocyclohexyl)(7-(4-(2-methoxyethyl)piperazin-1-yl)-6-(((3R,5R)-2-oxo-5(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1Hpyrazol-5-carboxamide (6.58 mg, 9.24 μmol, 13.3% yield, 99.7% purity) as a solid white. LCMS [M+H]+ = 710.3 m / z. Example 22: Preparation of Compounds 100 and 101

[00248] To a solution of N-((1S)-(7-chloro-6-(((5R)-5-methyl-2-oxopiperidin3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (220 mg, 401 μmol, 1.00 eq.) and 2-(3,6-dihydro-2H-pyran4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (169 mg, 803 μmol, 2.00 eq.) in dioxane (3.00 mL) and water (0.60 mL) were added Xphos-Pd-G3 (102 mg, 120 pmol, 0.300 eq.) and Cs2CO3 (262 mg, 803 μmol, 2.00 eq.) under a N2 atmosphere. The reaction mixture was stirred at 100 °C for 2 h. The reaction mixture was diluted with water (50.0 mL) and extracted with a mixture of dichloromethane and methanol (dichloromethane:methanol = 10:1).The combined organic layers were dried over anhydrous sodium sulfate and concentrated under pressure to provide a residue that was purified by Prep-TLC (SiO2, Dichloromethane: Methanol = 10:1) to provide N-((1S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro2H-pyran-4-yl)-6-(((5R)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (130 mg, 218 pmol, 54.4% of propional 870250091144, dated 06 / 10 / 2025, page 173 / 263. 165 / 184 duction) as a yellow solid. LCMS [M+H]+= 596.4 m / z.

[00249] To a solution of N-((1S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro2H-pyran-4-yl)-6-(((5R)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (130 mg, 218 μmol, 1.00 eq.) in THF (3.00 mL) was added Pd / C (230 mg, 216 μmol, 10.0% purity, 0.99 eq.) under a N2 atmosphere. The resulting suspension was degassed and purged with H2 three times. The reaction mixture was stirred under H2 (15 psi) at 25 °C for 2 h. The reaction mixture was filtered with THF (10.0 mL) and the filtrate was concentrated under reduced pressure to provide N-((1S)-(4,4-difluorocyclohexyl)(6-(((5R)-5-methyl-2-oxopiperidin-3-yl)methyl)-7-(tetrahydro-2H-pyran-4yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (120 mg, 201 μmol, 92.0% yield) as a white solid. LCMS [M+H]+= 598.3 m / z.

[00250] Compound 100 was isolated as the first eluent single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AD (250 mm x 30 mm, 10 µm); mobile phase: [CO2-i-PrOH (0.1% NH3 · H2O)]; B%: 25%, isocratic elution mode); (30.31 mg, 50.4 pmol, 25.1% yield, 99.4% purity) and was obtained as a white solid. LCMS [M+H]+= 598.2 m / z.

[00251] Compound 101 was isolated as the second eluent single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AD (250 mm x 30 mm, 10 µm); mobile phase: [CO2-i-PrOH (0.1% NH3 · H2O)]; B%: 25%, isocratic elution mode); (60.0 mg, 99.5 pmol, 49.5% yield, purity of Petition 870250091144, dated 06 / 10 / 2025, pp. 174 / 263 166 / 184 99.1%) and was obtained as a white solid. LCMS [M+H]+ = 598.2 m / z. Example 23: Preparation of Compounds 102 and 103

[00252] To a solution of N-((1S)-(7-chloro-6-(((5S)-5-methyl-2-oxopiperidin3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (166 mg, 302 μmol, 1.00 eq.) and 2-(3,6-dihydro-2H-pyran4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (190 mg, 908 μmol, 3.00 eq.) in dioxane (1.60 mL) and water (0.40 mL) was added Xphos-Pd-G3 (76.9 mg, 90.8 pmol, 0.300 eq.) and Cs2CO3 (197 mg, 605 μmol, 2.00 eq.) under a N2 atmosphere. The reaction mixture was stirred at 100°C for 2 h. The reaction mixture was diluted with water (40.0 mL) and extracted with ethyl acetate (3 x 40.0 mL).The combined organic layers were dried over anhydrous sodium sulfate and concentrated under pressure to provide a residue that was purified by Prep-TLC (SiO2, Dichloromethane: Methanol = 10:1) to give N-((1S)(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-pyran-4-yl)-6-(((5S)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (120 mg, 201.4 μmol, 66.5% yield) as a yellow solid. LCMS [M+H]+= 596.4 m / z. Petition 870250091144, dated 06 / 10 / 2025, pages 175 / 263 167 / 184

[00253] To a solution of N-((1S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro2H-pyran-4-yl)-6-(((5S)-5-methyl-2-oxopiperidin-3-yl)methyl)imidazo[1,2-b]pyridazin2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (120 mg, 201 μmol, 1.00 eq.) in THF (2.00 mL) was added Pd / C (214 mg, 201 pmol, 10% purity, 1.00 eq.) under a N2 atmosphere. The resulting suspension was degassed and purged with H2 three times. The reaction mixture was stirred under H2 (15 psi) at 25°C for 3 h. The reaction mixture was diluted with MeOH and filtered, the filtrate was concentrated under reduced pressure to provide N-((1S)-(4,4-difluorocyclohexyl)(6-(((5S)-5-methyl-2-oxopiperidin-3-yl)methyl)-7-(tetrahydro-2H-pyran-4yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (100 mg, 167 μmol, 83.0% yield) as a white solid. LCMS [M+ H]+= 598.4 m / z.

[00254] Compound 102 was isolated as the first eluent single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AS (250 mm x 30 mm, 10 µm); mobile phase: [CO2 - ACN / i-PrOH (0.1% NH3H2O)]; B%: 30%, isocratic elution mode); (56.84 mg, 92.9 pmol, 55.5% yield, 97.7% purity) and was obtained as a white solid. LCMS [M+H]+= 598.3 m / z.

[00255] Compound 103 was isolated as the second eluent single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AS (250 mm x 30 mm, 10 µm); mobile phase: [CO2 - ACN / i-PrOH (0.1% NH3H2O)]; B%: 30%, isocratic elution mode); (34.61 mg, 56.9 pmol, 34.0% yield, 98.4% purity) and was obtained as a white solid. LCMS [M+ H]+= 598.3 m / z. Petition 870250091144, dated 06 / 10 / 2025, pp. 176 / 263 168 / 184 Example 24. Preparation of Compound 118

[00256] A mixture of intermediate 1 (100.0 mg, 166 μmol, 1.00 eq.), 2(3,6-dihydro-2H-thiopyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (751 mg, 3.32 mmol, 20 eq.), K3PO4 (68.8 mg, 498 pmol, 3.00 eq.) and RuPhos Pd G3 (13.88 mg, 16.6 pmol, 0.1 eq.) in dioxane (2.00 mL) and H2O (0.5 mL) was degassed and purged with N2 three times, and then the mixture was stirred at 100°C for 2 h under microwave irradiation. The reaction mixture was diluted with 50.0 mL of H2O and extracted with EtOAc (50.0 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a residue, which was purified by preparative TLC (SiO2, DCM:MeOH = 10:1) to provide N-((S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-thiopyran-4-yl)-6(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (90.0 mg, 135.2 pmol, yield of 81.4%).

[00257] N-((S )-(4,4-difluorocyclohexyl) 1H-pyrazole-5-carboxamide was synthesized through Petition 870250091144, dated 06 / 10 / 2025, pp. 177 / 263 169 / 184 of the oxidation of N-((S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-thiopyran-4-yl)6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (70.0 mg, 105.2 μmol, 1.00 eq.) with m-chloroperoxybenzoic acid (39.9 mg, 231.4 μmol, 2.20 eq.) followed by olefin reduction of N-((S)-(4,4-difluorocyclohexyl) pyrazol-5-carboxamide with Pd / C under H2. The resulting residue was purified by Prep-HPLC to give N-((S)-(4,4-difluorocyclohexyl)(7-(1,1-dioxytetrahydro-2H-thiopyran-4-yl)-6(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidin-3-yl)methyl)imidazo[1,2-b]pyridazin-2yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (48.8 mg, 95.2% purity) as a white solid. LCMS [M+H]+ = 700.3 m / z. Example 25: Synthesis of selected IL-17 modulators

[00258] The compounds in Table 1 were synthesized analogously according to Examples 1 to 24.

[00259] In some respects, the present invention provides a compound of Formula (A) or Formula (I) selected from Table 1, or a pharmaceutically acceptable salt thereof. The compounds in Table 1 each represent a single isomer with known and labeled stereocenters. The absolute stereochemistry is unknown for the single isomers in Table 1 containing unlabeled stereocenters.

[00260] Table 1. Spectroscopy and structures for IL-17A modulators Petition 870250091144, dated 06 / 10 / 2025, pp. 178 / 263 170 / 184 No LCMS Structure 2 χ o / y X^^ hnX XXXo Xb fF F h 652.2 3 ,N. N XN / No Structure LCMS 7 ,N 0 / by XX\^ hnX nx» XX FFF ​​652.2 8 _N. X f1 íx 'kX\^\ HNX Jk .n, / X 0 x N / —\ o^^X \ / γχ '—4 hn^X^fff Xf F 645,5 9 N XN br Ϊ Ν<ΧΧχ\^Ν hnX 73⁄4. ,N......Xh\ 0 XN / —\ O.> / \ \ / 7 X '—k hnXX^f F Xf F 646,4 10 l\L °x ^Np Χ'-χ-',^Ν HN^\ Jk 0 x N / —\ XX —s HN^X^ 1 N Xp, 38 Xf XX^Í\^N ΗΙ\ΐχ TX z>—( 0 X> ,nX íX_ XN / —\ o^X \ / XX —k hnXL^fff Xf F 638,2 Petition 870250091144, dated 06 / 10 / 2025, p. 179 / 263 171 / 184 In the LCMS structure 12 ,Ν. 0. / N k HN^ T / )—( O ^k ,N^ ÍSA_ 1 N / \ 0>.J\ \ / HN^^FF TF 652,2 13 HN^ 1 T / )—( o ,N^Z ísA__ IN / --\ 0^ \ k F / F kkk^—4 N. / —n' k ° 1 HN=^ ,N-..7pk ° i N / —\ O<;Ã \_) hn^Pf F f kF F 653,0 15 O^| \=N hn^ JL .NkPP, 0 i N / —\ \__ / hn^L^fff kF F 667,3 16 o ] >n HN^ 1 . / )—( o 1 N / \ kkRk '—k hn^L^f F f kF F 667.4 No Structure LCMS 17 9^^ V=N hn^ / k ,n^ m_ = N / —\ o^^k \ / —k HN^^FFF kF F 667,4 18 N. .. / ~nk hN^ Jk ,N^^~rsA 0 i N / —\ k>Jk\ | \ / '—k HN^l FFF kF F 651,5 19 Ak '''P -^N'^ hn-^ / L ,Ν-kPp 0 f N / --\ k>k. \ / VRk '—k HN^L^F |LF kF F 687,3 20 N. \ ζ~·ν k N . fin^ T ( O / k ,N^Z k\_ i N / —\ Ck \ / kkRk '—k HN^k^FFF kF F 666,4 21 O, HN^ / 1. / )—( o / k Jk / s;\__ i N / —\ O>,j\ \ / kiRn F '^^F HN Petition 870250091144, dated 06 / 10 / 2025, p. 180 / 263 172 / 184 No LCMS Structure 22 N„ CP Η NPT ' / )—( o A, ísj\__ i N / —\ O, A \ / T <Rn '—s hC^C-F F F Af F 637,4 23 c CF | \ ))—( o A. ÍS}\__ 1 N / \ CA. Á. \ / Ym '—s HN^^F F F Yf F 623,2 24 ,N. 0 Cp HN—4 JL AÁCa ° 4 N / --\ 0., / ,. \ / Vs / ] '—s HN^^F F F T~F F 623,4 25 o y x ° f N / Vf θ<^ / \ \ / 'F hn..CF<f Pf F 653,4 26 o cP hn—4 A. ,naW 0 f N / VF \ / ^F \— / r hnCF^f Tf 653,2 No Structure LCMS 27 V 'Á, or cP hn^ x yyy^0 f N ^VF \ / F hnCCF / F Pf F 667.3 28 V 'Á, or cP A. ,ná <w7l0 f N / VF \ / F ^pRpi \ / r HN^C / F Ff F 667,3 29 ty c \ / \ / ^~ó 667,3 30 9^C pN F CáCw^ 0 f N / y^ 0<s^P\ \ / 'F ywp \— / r ΗΝ^Ρ,Ρ Pf F 667,2 31 NL ° y C^n..^\^ hnP ,nPcF ° i n / —\ θ<Ρ\ \ / vRn '—s HN^C^F |L F Τ> F 667.4 Petition 870250091144, dated 06 / 10 / 2025, p. 181 / 263 173 / 184 No Structure LCMS 32 N. / Z^n' η 0 aZvAaN HN^ 1 / )—( O ,N^ / AA__ i N / —\ ca_A \ / aarZ '—s FF af F 667,3 33 1 'Na, °A HN—( 1 T , IN / )—\ o . 7 íR / 1 '—< HN^^FF Zf F 667,4 34 1 -na ó Cz a / N-^ HN—( 1 . / )—( o 93⁄4 .NA AA_ i N / —\ 0. \ / HN^i^FFF TF 667,4 'ax^n 1— 7 ,na / aa__ i N / —\ \ / vRn '—< hn^^f F f Zf F 665,3 36 N / —Ν' y ^ααα,Ν HN A 1 ' / )—( o Ja j. / AA_ I n / \ O,.J\ \ / AARAi '—4 hn^60 No Estrutura LCMS 37 l\L ^n' a 0 1 W \ ΓΖΖ Xo Ja ,N^7 ísA__ IN / —\ Oa>a \ / AARA ' 4 HN^A / FF AF F 653,5 38 ^=n aN-.A'vN HN^ 1 । / )—( o >A ,N^A 1SA__ IN / \ OaZa \ / Vkn \—Z HN . Z·. / FFFKF 667,3 39 _ / ^N'o \=n JL ° = N / —\ \ / aAsa \— / HN <^·. FFF Zf F 667,3 40 F. 9 f-Và >=n hn^ I / >—( 0 >A . Petition 870250091144, of 06 / 10 / 2025, page. 182 / 263 174 / 184 No Estrutura LCMS 42 o-, AC Up AN hn^ ,νΑΑΧ 0 1 N / \ \ / vR / 1 '— hn.Af f F Af F 679,4 43 N. o-^ HN < T \ / )—( Ο Af ,N^ / SA_ 1 N / \ 0^ \ / Ym '—s ην< / f f Tf 665,3 44 A--pN'O Pp > N \FxA\n HN^f | Γ —ro A- ,n A mi N / —\ \ / Ym '—s ΑρΑγ |LF Af F 652,4 45 Py )=n 1 ϊ P—( o A- ,ny m_ i N / —\ OJ \ / Ym '—κ FXvf F f Af F 652,4 46 N. Y ΑχζΤ'χ.,Ν ΗΝ^ T ' / )—( o A Υ / / SÃ_ IN / —\ \ / AC λ—s HN^FFF Af F 636,5 No LCMS Structure 47 .0, ,N. Oh A FY.YY hn < 1 1 / ) o xN^ ísà_ 1 N / —\ J\ \ / 7 ^Γί \—h hnA> / FF f Tf F 693,5 48 λ. N. OA / ~~~NA HN^ T h- / >—( O f N / —\ CaO\ \ / Wn x—4 hnAAf ff Pf F 693,6 49 N. A CF 1 . / )—( o A ,nA A_ i N / —\ o<.A. \ / AC x—s hnA\ <f f f Af F 679,4 50 N, , N Α'Ν' / \ / Oji / F <on>^\r^N HNA TA ,)—( o A- A i N / —\ o<.A. \ / TiRi 1 '—s hn^cL / F ff Tf 679,4 51 N. ^N' p °zF W hnA \ T / AA o A- ,nA A_ i N / —\ o. A.\ A. \ F / 4 hn A / F hn A_ ff Tf 679,4 51 N. ^N' p °zF W hnA \ T / AA o A- ,nA A_ i N / —\ o. 665.4 Petition 870250091144, of 06 / 10 / 2025, p. 183 / 263 175 / 184 No LCMS Structure 52 HN— 1 . / )—( o A, ,NA ÍSA__ f N / —\ O. 1 \ / Vm '—k FF kF F 665,3 53 N. k 0 1 Z \k\kAN HN^ 1 ' / )—( 0 Aí kl fs;\__ IN / —\ ΟλΛ \ / x—k hnJ^ F F 65 fF 65 kF Z^N'O ? 1 / \ / \^k\^;N HN— 1 Ϊ / )---( o ,nA m_ IN / \ ο,Λ \ / hn^^Zf F f kp F 666,6 55 ci cP HN^, A. .LcCí5) 0 fn / F \γ γ γ / r HN^C^ kF F 652.4 56 o. CA / 'yN HN—( X. ,νΖζΖ ° f N ZZF \ / ^F HN^üC / FT^FF 652.3 No Structure LCMS 57 C^N'o \=N Cs- ,N^kd\k ° 1 N < VF \ / ^F HNdk.F kF F 666,3 58 N. °c ^Np \^C^í\^N HN^ TF / )—( O ,N^ / L N i—\\__ <Rk '—k hn,. / Lf F TF 636,4 59 C^N'o \=N C^\^ FIN^ A. ° f N / Vf \ / ^F ^ρκΛι / r HN1Í1C / F kF F 666,5 60 N. \ / \ Z^N η N 1 HnZ Γ F o Zk ,N-< / ÍSA__ i N / \ CZ J\ \ / 7 m x—< hnC^f F f Pf F 665,5 61 N. / -n' k HN^ / k ,νΖΖ 0 1 N / —\ \ / 7 ÍRki '—k hnHZf F f kF F 651,4 Petition 870250091144, dated 06 / 10 / 2025, p. 184 / 263 176 / 184 No Structure LCMS 62 N / ^~N' —N 1 / HN 4 TF / )—( 0 ,N.# ÍS;\__ IN / —\ \ / HN^k / FFF Af F 651,4 63 ,N. 0 / N y / HN2^ A >A f N. / F ^AF h6 A \—A 0. A \A\ hnA A ,nÀ fnn F 0<^X\ \ / 'F Ym x / rhN.A <F Af F 652,3 65 XXo X < X- J TX ζη M U. Le o / Az \— / 1 652,2 66 CXo X C ktO Z X KzZ . Xz λΧΧ o >A 2 \— / j T 652.3 No Estrutura LCMS 67 N. °Ί ZA xA\y\^ hn^ A ,νААА_° f N kXF θ<^Χ\ \ / 'F FIN^A / F Af F 638,6 68 CA° A ( k AJ z X AzZ u. Xz / X^Xk X OX 638,4 69 / °AX^ hnA A. ,N'...AAs / ° f N < VF θ<^Χ\ \ / Xf XX / r HN AA <F Af F 652,5 70 AVo hnA A- ,n^A\w ° 1 N / Vf θ<^Χ\ \ / 'F hnAxf Af F 652,3 71 zX A° kXvA -A X) Ή X z Xi \ i A f / x°A 638,5 Petition 870250091144, de 06 / 10 / 2025, pág. 185 / 263 177 / 184 No Estrutura LCMS 72 N. °Ι ΑΑχ^χ^Ν HN— X- ,nXX_ 0 1 N Οχ / \ \ / 'F xx / p \— / r HN^X / F Xf F 638,4 73 / \ N„ Ρη An Xxkx ,N HN^ X ,ΧΧΧι'β; ° f N - vF \ / ^F XXRp x / r HN^XF Xf F 652,5 74 P~Z uu W1 652,3 75 \ N àn' X 0 1 ρΡ xPyA^N HN— 1 Γ / )—( 0 Αχ ,N·^ (S)\__ f N / —\ Οχ J\ \ / n λ—4 ΗνΑ / F Tf f 666,4 76 a cp \Αχ^ HNX 1 ' / )—( 0 A. ,n^zmi N / —\ 0, X \ / VR / 1 '—s Hn Af FF Xf F 650.5 No Structure LCMS 77 N. / -NX hn— T / )—( o / 1⁄4 ísA__ í N / —\ O- J\ \ / VRX] —K hn^L^f FT^FF 667,4 78 N. / ^N / °PPN\^\\^N HnA 1 ^ J '_ / )—( Οχ Jx \ / hnXXf ff Xf F 667,3 79 N. / °^ / O HN^ T ' / )— / O ,N^Z m_ IN / \ Οχ X \ / VR / 1 '—k hnX^fff Xf H-N f 653,3— XX N 80 A Z Nx ,ΝχΧ7 ÍS)\__ í N / —\ Οχ j\ \ / X 1 —X HN,XF FFFF 692,3 81 V ,N cxp ''xN-.^-xN HN AT ' / )—( oi N / —\ f —χ / XfΧA7χ 679.3 Petition 870250091144, dated 06 / 10 / 2025, p. 186 / 263 178 / 184 No Structure LCMS 82 V Ύ ^NP Jk ° i N / —\ o>.Y \ / YY '—s HN^Y^FFF Yf F 692,4 83 l\L 7 z \=J HN^ ,Ν^Ζ (Υ__ N / —\ \,8 Y. vRn^ —8 F 3 k hnY / ~n' 7 i° W 1\^Y^xxn HN^ JL ,Ν^. / Υ7·, ° IN / \ o^Y\ \ / γζγ '—k HN^Y^FF Yf F 652,4 85 FL ^n' 7 Γ 0 w Y— N.^;Y_ / hnY / —\ O^Y\ \ / 7<Ύ '—k HN^Y^FF TF 652.5 86 CY° f7 / Γ I γ \ > M - ο γγ 630.5 No Estrutura LCMS 87 N. / ^N 7 ° 1 —hn^ IN / \ \ / 7iR / 1 '—k hn^Y^fff YF F 680,4 88 N Λ~Ν' 7 ° 1 γ= / HN 4 1 ' / )—( 0 Y^ ,n^ / Y,_ i N / —\ ck \ / YíRl | '—k hn^Y^ff F l^FF 680.4 89 N. OY Yn HnY X yyy γ Y. ,nY m_ f N / —\ \ / ΗΝ,,γY^ρ ff Yf F 653.5 90 \ N\ / ~N 7 o Y \=N HN—( TY ,)—( o Y. ,nY m_ ι N / —\ 0. \ / YíRn '—k ηn<7 F f Yf F 667.4 91 / \ N. 7 0 i \.Y\^ hn—{ 1 Y / )—( o ,νΥ <Υ_ ι N / —\ \ / hn^L^fff Yf F 664,5 Petition 870250091144, de 06 / 10 / 2025, pág. 187 / 263 179 / 184 No Estrutura LCMS 92 ζ3γ° pZ Λ Z^ / LJ Ζ A Μ - Ο h 700.4 93 ι / ? Γ°\ z-—\ \ / ζρ m Η F Ζ Π rr '' °Ay 700.4 94 Ν. ^ν' η [ 0 W °·ΧΑ\^ ΗΝ^ Τ / )—( ο ,ν.# m ι ​​Ν / —\ 0. Jx \ / T <Rn '—κ F F TF 654,4 95 Π p Ο zA m fA F z 654,4 96 ,N. fr hn^ Ãí ,ν^ΑΑ ° f N / —\ Ο, / χ \ / ZZspi '—K hn^L^f f f Zf F 667,3 No Structure LCMS 97 / X. / ZN / 0 HnA T ' / )—( O ,n^Z m_ N / —\ HN^k / F ff Zf F 667,3 98 N7, h°^ ^Nx^x^N HN^ í Ϊ / )—( O / Z ,n^z m_ 1 N / \ o>'—ÍFFR P H1 \ / T 639.3 99 −N <x n. / X / X / ~~N 7 ^χχΝχ^#^\^Ν HN^ 1 F z)—( o ,J ,Ν-^Z \__ I N / --\ \__) ΗΝχ / χχΡ F F TF 710,3 100 x A r°\ ( ) / zM 7 A F· 598,2 101 Nx / N Z 0 i AA\xZ\^N HN^ Λ ΧΖΛ 0 O.;x / \ \__) f F 598,2 Petition 870250091144, dated 06 / 10 / 2025, p. 188 / 263 180 / 184 No Structure LCMS 102 [Λ ΗνΥ í k 598.3 103 N. 7 yJJ k / Y\ / HN^ T / )—( 0 ,nx \_ - N / —\ \__) HN^ / k, FF N 598,3 104 HNγo F νΥΛ θ 708.3 105 Y fYj Y k-YP 0 - N / —\ A.0 \_) F . c. ΥνΗ FFXF 687,4 106 N / —N' ΛνΧΑΑ H,NY YY -nYL 0N / —\ A.0 \_) K ,.k^NH FFF^' ​​F 651,2 No Estrutura LCMS 107 z n H,Nkf 1 1 / >—( O N )---\ \__) F\ .-'k / F F F^l F 665,4 108 kP cço>rf ^^0 \_ / K„.Ynh F f F 667,3 109 N. / —Ν' y r-N^r^A H?A fX / 1 / )—\ o F / ^7 Α,.νΧ \_s F í N ) \ \__) F . F F F^ F 673,3 110 F t, N Z \=J xk^\^N HnY A ΧΖΛ 0N / —\ \__ / F^,.-^^NH F F f7 F 707,3 111 ftH' Á 625,3 Petição 870250091144, de 06 / 10 / 2025, pág. 189 / 263 181 / 184 No. Estrutura LCMS 112 n . / — n' η NH z \=J HnA W \__) R ,.Ι^ΝΗ F F A F 611,3 113 A- HNA Mã \__ / F F F^ F 651,3 114 ,N N z vA hnA 1 T ( 0 A'N^A A.0 \_ / R ,.Ι^ΝΗ F F A 667,3 115 FtF NH ' \=J HN — A AV f N / —\ A.0 \_) F^.- k^NH F F A F 679,3 Exemplo 26. Ensaio de células HEK-Blue IL-17A / A No. Estrutura LCMS 116 Ftí N Z \=J A^^-N hnA r T / W Xo N / —\ ) F\ ..· ·'^ F F A F 693,3 117 FTF Δ ηνΑ* í 1 / )---( O = N / —\ ) ρ,,. Ι^^ΝΗ F F A F 719,3 118 J ‘i _ yA o A. / ω ’ °p) A 700,3

[00261] The HEK-Blue IL-17A reporter cell line (Fisher No. NC1408637) was used for cell-based IL-17A / A inhibition assays. Cells were cultured and prepared for the assays according to the manufacturer's instructions. This cell line consists of HEK 293 cells that were engineered to express IL-17RA, IL-17RC, and the adaptor molecule Act1, whose combination, when stimulated by IL-17A / A or IL-17A / F, activates an NFkB promoter and drives the expression of the recombi gene. Petition 870250091144, dated 06 / 10 / 2025, page 190 / 263 182 / 184 of Secreted Alkaline Phosphatase (SEAP). The cell medium is then added to a development reagent (Quanti-Blue substrate, Fisher No. NC9711613) and read at A630.

[00262] The compounds were dispensed in DMSO to an empty, transparent 384-well tissue culture plate at a titration ranging from 10 μM to 27 pM, with DMSO added to each well to a final concentration of 0.1%. Cells were then added to the plate (45 pL / well at a concentration of 280,000 cells / mL). IL17A / A (Genscript #Z03228) or IL17A / F (R&D Systems) was added to the plate to a final concentration of 5 ng / mL and a final well volume of 50 pL. The cells, the compound, and IL-17A / A or IL17A / F were then incubated for 20 hours before removal from the medium for SEAP analysis. The resulting inhibition curve was then analyzed using Dotmatics' integrated 4-parameter tuning screening protocol to provide IC50 values.

[00263] Table 2 includes IC50 values ​​for IL-17A / A inhibition of selected compounds; with compounds having an IC50 of A <100 nM; B 100 to 1000 nM; and C >1000 nM. Table 2: IL-17 A / A inhibition data for selected compounds Compound No. IC50 of AA 1 A 2 B 3 B 4 B 5 A 6 A 7 B 8 B Compound No. IC50 of AA 9 C 10 B 11 B 12 A 13 A 14 A 15 A 16 A Compound No. IC50 of AA 17 B 18 A 19 A 20 A 21 A 22 A 23 A 24 C Petition 870250091144, dated 06 / 10 / 2025, pp. 191 / 263 183 / 184 Compound No. IC50 of AA 25 A 26 A 27 A 28 A 29 A 30 A 31 A 32 B 33 A 34 A 35 A 36 A 37 A 38 A 39 C 40 B 41 B 42 B 43 B 44 A 45 A 46 A 47 A 48 A 49 A 50 A 51 A 52A Compound No. IC50 of AA 53 A 54 A 55 A 56 A 57 A 58 B 59 A 60 B 61 B 62 B 63 A 64 A 65 A 66 A 67 A 68 A 69 A 70 A 71 A 72 A 73 A 74 A 75 A 76 A 77 A 78 A 79 A 80A Compound No. IC50 of AA 81 A 82 A 83 A 84 A 85 A 86 A 87 A 88 A 89 B 90 A 91 A 92 B 93 A 94 B 95 A 96 C 97 A 98 B 99 A 100 B 101 A 102 B 103 A 104 A 105 A 106 A 107 A 108 A Petition 870250091144, dated 06 / 10 / 2025, pp. 192 / 263 184 / 184 Compound No. IC50 of AA 109 A 110 A 111 A 112 A Compound No. IC50 of AA 113 A 114 A 115 A 116 A Compound No. IC50 of AA 117 A 118 A< / on>

Claims

1. Compound, characterized in that it is represented by the structure of Formula (A): (R1)P (A), or a pharmaceutically acceptable salt thereof wherein: X is selected from N or CR2; A is selected from (a) and (b): (a) C1-10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11A, -SR11A, -N(R11A)2, C(O)R11A, -C(O)N(R11A)2, -N(R11A)C(O)R11A, -C(O)OR11A, -OC(O)R11A, S(O)R11A, -S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN; (b) -(CR'R”)m(3- to 10-membered heterocycle), -(CR'R'')m(C3-10 carbocycle), -O(CR'R”)m(3- to 10-membered heterocycle), and -O-(CR'R'')m(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, -CN;C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents. Petition 870250091144, dated 06 / 10 / 2025, page. 224 / 263 2 / 29 selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), -CN, and C1-10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11A, -SR11A, -N(R11A)2, -C(O)R11A, C(O)N(R11A)2, -N(R11A)C(O)R11A, -C(O)OR11A, -OC(O)R11A, -S(O)R11A, S(O)2R11A, -NO2, =O, =S, =N(R11A), and -CN;and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN; and C1. 10 optionally substituted alkyl with one or more substituents independently selected from: halogen, -OR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; each R' is selected from hydrogen, halogen, -OR18, -N(R18)2, -C(O)R18, C(O)N(R18)2, -NO2, -CN; and C1-6 optionally substituted alkyl with one or more halogens, -OR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -NO2, and -CN; each R'' is selected from hydrogen, halogen, -OR19, -N(R19)2, -C(O)R19, C(O)N(R19)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more of halogen, -OR19, -N(R19)2, -C(O)R19, -C(O)N(R19)2, -NO2, and -CN;B is selected from -C(R5)3 and C3-10 carbocycle, wherein the C3-10 carbocycle is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2R12, -C(O)OR12, -OC(O)R12, S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN; C1-10 alkyl and C3-10 carbocycle, any of which is optionally substituted with one or more substituents independently selected from Petition 870250091144, dated 06 / 10 / 2025, p. 225 / 263 3 / 29 selected halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN, C3-10 carbocycle and heterocycle of 3 to 10 members; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -NO2, =O, =N(R12), and -CN;each R5 is independently selected in each occurrence of (i), (ii), and (iii): (iv) hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​S(O)R13, ​​-S(O)2R13, -NO2, -CN; (v) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), -CN; and (vi) C3-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), -CN;and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​S(O)2R13, -NO2, =O, =S, =N(R13), and -CN; each R1 is independently selected in each occurrence of: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, Petition 870250091144, dated 06 / 10 / 2025, page. 226 / 263 4 / 29 C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2R14, -C(O)OR14, -OC(O)R14, S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle;The C3-10 carbocycle and heterocycle of 3 to 10 members are each optionally substituted with one or more substituents selected from: halogen, -OR14A, -SR14A, -N(R14A)2, -C(O)R14A, -C(O)N(R14A)2, -N(R14A)C(O)R14A, -C(O)OR14A, OC(O)R14A, -S(O)R14A, -S(O)2R14A, -NO2, =O, =S, =N(R14A), and -CN; or two R1 substituents can link to form a C3-6 carbocycle or 3- to 6-membered carbocycle, wherein the C3-6 carbocycle and 3- to 6-membered carbocycle are each independently substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1-10 alkyl and C3-10 carbocycle, the C1-10 alkyl and C3-10 carbocycle are each independently substituted with one or more independently selected halogen substituents, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN;R2 is selected from: hydrogen, halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, N(R15)C(O)R15, -N(R15)S(O)2R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR15, -SR15, -N(R15)2, -C(O)R15, C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, =O, =S, =N(R15), and -CN; Petition 870250091144, dated 06 / 10 / 2025, p. 227 / 263 5 / 29 or R2 and an R1 can link to form a 3- to 6-membered carbocycle, in which the 3- to 6-membered carbocycle is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR20, -N(R10)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), and -CN;Each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, N(R16)S(O)2R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR16, -SR16, -N(R16)2, -C(O)R16, C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, NO2, =O, =S, =N(R16), and -CN; L is selected from a linkage, -O-, and C1-6 alkylene optionally substituted with one or more independently selected halogen substituents, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, CN;Ring D is selected from C3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, Petition 870250091144, dated 06 / 10 / 2025, p. 228 / 263 6 / 29 S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle;and C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and optionally substituted C1-6 alkyl with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; R11, R11A, R12, R13, R14, R14A, R15, R16, R17, R18, R19, R20, and R21 are each independently selected at each occurrence of: hydrogen;C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; m is selected from 0, 1, and 2; z is selected from 1 and 2; n is selected from 1, 2, and 3; ep is selected from 0, 1, 2, 3, 4, 5, and 6.

2. Compound or salt, according to claim 1, characterized by the fact that L is selected from a C1-6 alkylene bond optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, or -CN.

3. Compound or salt, according to claim 2, characterized in that L is C1-6 alkylene optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, O-C1-6 haloalkyl, -NH2, -NO2, =O, or -CN.

4. Compound or salt, according to claim 3, characterized in that L is C1-3 alkylene optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, O-C1-6 haloalkyl.

5. Compound or salt, according to claim 4, characterized in that L is selected from methylene and ethylene, each of which is optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl.

6. Compound or salt, according to claim 5, characterized in that L is methylene.

7. Compound or salt, according to any one of claims 1 to 6, characterized in that ring D is a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN, C3-10 carbocycle and heterocycle Petition 870250091144, dated 06 / 10 / 2025, p. 230 / 263 8 / 29 of 3 to 10 members.

8. Compound or salt, according to claim 7, characterized in that ring D is a saturated 4- to 7-membered heterocycle optionally substituted with one or more independently selected halogen, C1-6 alkyl, and C1-6 haloalkyl substituents.

9. A compound or salt, according to any one of claims 1 to 9, is selected from:

10. Compound or salt, according to claim 1, characterized in that L is a bond.

11. Compound or salt, according to claim 1 or 10, characterized in that Formula (A) is represented by the structure of or a pharmaceutically acceptable salt thereof, wherein: A is selected from -(CR'R")m(3- to 10-membered heterocycle), -(CR'R'')m(C3-10 carbocycle), -O-(CR'R")m(3- to 10-membered heterocycle), and -O-(CR'R")m(C3-10 carbocycle), the 3- to 10-membered heterocycle and C3-10 carbocycle being each independently substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, Petition 870250091144, of 06 / 10 / 2025, page.C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11,N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN;and C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN; each R' is selected from hydrogen, halogen, -OR18, -N(R18)2, -C(O)R18, C(O)N(R18)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more halogen, -OR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -NO2, and -CN; each R'' is selected from hydrogen, halogen, -OR19, -N(R19)2, -C(O)R19, C(O)N(R19)2, -NO2, -CN; and C1-6 alkyl optionally substituted with one or more of halogen, -OR19, -N(R19)2, -C(O)R19, -C(O)N(R19)2, -NO2, and -CN;B is selected from -C(H)(R5)2 and C3-10 carbocycle, where the C3-10 carbocycle is optionally replaced with one or more substituents selected independently from: Petition 870250091144, 06 / 10 / 2025, p. 232 / 263 10 / 29 halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, N(R12)C(O)R12, -N(R12)S(O)2R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN; C1-10 alkyl and C3-10 carbocycle, any of which is optionally substituted with one or more independently selected halogen substituents, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -S(O)R12, -S(O)2R12, -NO2, =O, =S, =N(R12), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR12, -N(R12)2, -C(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -C(O)OR12, -OC(O)R12, -NO2, =O, =N(R12), and -CN;each R5 is independently selected in each occurrence of (i), (ii), and (iii): (iv) halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, -CN; (v) C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, =N(R13), -CN; and (vi) C3-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, ​​-C(O)N(R13)2, N(R13)C(O)R13, ​​-N(R13)S(O)2R13, -C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​-S(O)2R13, -NO2, =O, =S, Petition 870250091144, dated 06 / 10 / 2025, page 233 / 263 11 / 29 =N(R13), -CN;and C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR13, -SR13, -N(R13)2, C(O)R13, ​​-C(O)N(R13)2, -N(R13)C(O)R13, ​​-C(O)OR13, -OC(O)R13, ​​-S(O)R13, ​​S(O)2R13, -NO2, =O, =S, =N(R13), and -CN; Each R1 is independently selected on each occurrence of: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, N(R14)C(O)R14, -N(R14)S(O)2R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, NO2, =O, =S, =N(R14), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -S(O)R14, -S(O)2R14, -NO2, =O, =S, =N(R14), and -CN;or two R1 substituents may link to form a 3- to 6-membered carbocycle, in which the 3- to 6-membered carbocycle is optionally substituted with one or more substituents independently selected from: halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, =S, =N(R20), and -CN; R2 is selected from hydrogen, halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, C(O)N(R15)2, -N(R15)C(O)R15, -N(R15)S(O)2R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, NO2, -CN; and C1-6 alkyl optionally substituted with one or more independently selected halogen substituents, -OR15, -SR15, -N(R15)2, C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -S(O)R15, -S(O)2R15, -NO2, =O, =S, =N(R15), and -CN;or Petition 870250091144, dated 06 / 10 / 2025, p. 234 / 263 12 / 29 R2 and R1 can link to form a 3- to 6-membered carbocycle, in which the 3- to 6-membered carbocycle is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), -CN; C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR20, -N(R10)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, =S, =N(R21), and -CN; each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, N(R16)S(O)2R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, -NO2, -CN;and optionally substituted C1-6 alkyl with one or more independently selected halogen substituents, -OR16, -SR16, -N(R16)2, -C(O)R16, C(O)N(R16)2, -N(R16)C(O)R16, -C(O)OR16, -OC(O)R16, -S(O)R16, -S(O)2R16, -NO2, =O, =S, =N(R16), and -CN; Ring D is selected from C3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle;and optionally substituted 3- to 10-membered carbocycle and heterocycle Petition 870250091144, 06 / 10 / 2025, p. 235 / 263 13 / 29 with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), -CN; and optionally substituted C1-6 alkyl with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, -N(R17)S(O)2R17, -C(O)OR17, OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, =O, =S, =N(R17), and -CN; R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, and R21 are each independently selected at each occurrence of: hydrogen;C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6 alkyl, -O-C1-6 haloalkyl, -NH2, -NO2, =O, and -CN; m is selected from 0, 1, and 2; n is selected from 1 and 2; ep is selected from 0, 1, 2, 3, 4, 5, and 6.

12. Compound or salt, according to claim 11, characterized in that n is 1.

13. Compound or salt, according to claim 11 or 12, characterized in that Formula (I) is represented by the structure of Formula (Ia): Petition 870250091144, dated 06 / 10 / 2025, p. 236 / 263 14 / 29 (Ia).

14. Compound or salt, according to claim 11, characterized in that n is 2.

15. Compound or salt, according to claim 11 or 4, characterized in that Formula (I) is represented by the structure of Formula (Ib): ( D ) X—B R3 IJ o R3tVN^ / HN^ °V\2 AHN^J (r1)p (Ib).

16. Compound or salt, according to any one of claims 11 to 0, characterized in that m is 1.

17. Compound or salt, according to any one of claims 11 to 0, characterized in that R' and R'' are each independently selected from hydrogen, halogen, -OR18, -N(R18)2, -CN, C1-3 alkyl, and C1-3 haloalkyl.

18. Compound or salt, according to claim 0, characterized in that R' and R'' are each independently selected from hydrogen, halogen, C1-3 alkyl, and C1-3 haloalkyl.

19. Compound or salt, according to claim 0, characterized in that R' and R'' are each independently selected from hydrogen and halogen.

20. Compound or salt, according to any one of claims 11 to 0, characterized in that m is 0. Petition 870250091144, dated 06 / 10 / 2025, pp. 237 / 263 15 / 29 21. Compound or salt, according to any one of claims 11 to 0, characterized in that A is a 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, -CN; C1-10 alkyl optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, NO2, =O, =S, =N(R11), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -NO2, =O, =N(R11), and -CN;and C3-10 carbocycle and heterocycle of 3 to 10 members, each of which is optionally substituted with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.; 22. Compound or salt, according to any one of claims 0 to 0, characterized in that A is a 5-membered heteroaryl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, Petition 870250091144, dated 06 / 10 / 2025, p. 238 / 263 16 / 29 -NO2, -CN; and optionally substituted C1-6 alkyl with one or more independently selected halogen substituents, -OR11, -SR11, -N(R11)2, C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents selected from: -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, and -CN.

23. Compound or salt, according to claim 0, characterized in that A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any of which is optionally substituted with one or more C1-6 alkyls optionally substituted with one or more substituents independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -C(O)OR11, -OC(O)R11, -NO2, and -CN.

24. Compound or salt, according to claim 0, characterized in that A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -NO2, and -CN.

25. Compound or salt, according to claim 0, characterized in that A is selected from pyrazolyl optionally substituted with methyl, ethyl, isopropyl or propyl.

26. Compound or salt, according to claim 0, characterized in that A is selected from: N and Petition 870250091144, dated 06 / 10 / 2025, page 239 / 263 17 / 29 27. Compound or salt, according to any one of claims 10 to 0, characterized in that A is a 5-membered heteroaryl optionally substituted with a C3-10 carbocycle optionally substituted with one or more independently selected halogen substituents, OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, OC(O)R11, -S(O)R11, -S(O)2R11, -NO2, =O, =S, =N(R11), -CN; and optionally substituted C1-6 alkyl with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -NO2, =O, =N(R11), and -CN.

28. Compound or salt, according to claim 0, characterized in that A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any of which is optionally substituted with a saturated C3-6 carbocycle optionally substituted with one or more substituents independently selected from halogen, OR11, -N(R11)2, -C(O)R11, -NO2, -CN, C^alkyl, and C^haloalkyl.

29. Compound or salt, according to claim 0, characterized in that A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl are each optionally substituted with halogen, C1-6 alkyl, and C1-6 haloalkyl.

30. Compound or salt, according to claim 0, characterized by the fact that A is selected from v, 0, and FF.

31. Compound or salt, according to any one of claims 1 to 0, characterized in that B is -C(H)(R5)2. Petition 870250091144, dated 06 / 10 / 2025, pp. 240 / 263 18 / 29 32. Compound or salt, according to claim 0, characterized in that each R5 of -C(H)(R5)2 is independently selected from: halogen, -OR13, -N(R13)2, -C(O)R13, ​​-C(O)OR13, -NO2, -CN; C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR13, -N(R13)2, -C(O)R13, ​​-C(O)OR13, -NO2, =O, =S, =N(R13), and -CN; and C3-10 carbocycle optionally substituted with one or more independently selected halogen substituents, -OR13, -N(R13)2, -C(O)R13, ​​-C(O)OR13, -NO2, =O, =S, =N(R13), -CN, C1-6 alkyl, and C1-6 haloalkyl.

33. Compound or salt, according to claim 0, characterized in that each R5 of -C(H)(R5)2 is independently selected from C3-6 carbocycle optionally substituted with one or more independently selected substituents of halogen, -OR13, -N(R13)2, -C(O)R13, ​​-C(O)OR13, -NO2, =O, =S, =N(R13), -CN, C1-6 alkyl, and C1-6 haloalkyl.

34. Compound or salt, according to any one of claims 11 to 0, characterized in that B is C6-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR12, N(R12)2, -C(O)R12, -NO2, =O, =S, =N(R12), -CN, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, N(R12)2, -C(O)R12, -NO2, =O, =S, =N(R12), and -CN.

35. Compound or salt, according to claim 0, characterized in that B is selected from cyclohexyl and cycloheptyl, or each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, N(R12)2, -NO2, -CN, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, N(R12)2, -C(O)R12, -NO2, =O, Petition 870250091144, 06 / 10 / 2025, p. 241 / 263 19 / 29 =S, =N(R12), and -CN.

36. Compound or salt, according to claim 0, characterized in that B is selected from: l, f, eff.

37. Compound or salt, according to any one of claims 11 to 0, characterized in that ring D is a C3-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN.

38. Compound or salt, according to claim 0, characterized in that ring D is a saturated C3-6 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl.

39. Compound or salt, according to claim 0, characterized in that ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, each of which is optionally substituted with halogen, C1-6 alkyl, and C1-6 haloalkyl.

40. Compound or salt, according to claim 0, characterized in that ring D is selected from: , , and 41. Compound or salt, according to any of the claims 11 to 0, characterized in that ring D is a 3 to 10 membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-10 alkyl and C3-10 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN.

42. Compound or salt, according to claim 0, characterized in that ring D is selected from a 3- to 7-membered monocyclic heterocycle and a 5- to 10-membered bicyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN; and C1-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more independently selected halogen substituents, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, and -CN.

43. Compound or salt, according to claim 0, characterized in that ring D is a 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR17, -SR17, -N(R17)2, -C(O)R17, -C(O)N(R17)2, -N(R17)C(O)R17, N(R17)S(O)2R17, -C(O)OR17, -OC(O)R17, -S(O)R17, -S(O)2R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl.

44. Compound or salt, according to claim 0, characterized in that ring D is selected from pyridinyl and pyrimidinyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl.

45. Compound or salt, according to claim 0, characterized in that ring D is selected from 46. ​​Compound or salt, according to claim 0, characterized in that ring D is selected from a saturated 3- to 6-membered heterocycle and an unsaturated 3- to 6-membered heterocycle, either of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-6 alkyl, C1-6 haloalkyl, and C3-6 carbocycle.

47. Compound or salt, according to claim 0, characterized in that ring D is an optionally substituted 3- to 6-membered unsaturated heterocycle with one or more independently selected halogen, C1-6 haloalkyl, and C3-6 carbocycle substituents.

48. Compound or salt, according to claim 0, characterized in that ring D is selected from 2,5-dihydrofuranyl and 3,6-dihydro-2H-pyranyl.

49. Compound or salt, according to claim 0, characterized in that ring D is selected from e'.

50. Compound or salt, according to claim 0, characterized in that ring D is a 3- to 6-membered heterocycloalkyl optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocyclo. Petition 870250091144, dated 06 / 10 / 2025, pp. 244 / 263 22 / 29 51. Compound or salt, according to claim 0, characterized in that ring D is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyran, dioxanyl, morpholinyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl and C3-6 carbocycle; and R17 is selected from hydrogen, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle.

52. Compound or salt, according to claim 0, characterized in that ring D is selected from 53. Compound or salt, according to claim 0, characterized in that ring D is selected 54. Compound or salt, according to claim 0, characterized by the fact that ring D is selected —N Petition 870250091144, dated 06 / 10 / 2025, pp. 245 / 263 23 / 29 55. Compound or salt, according to claim 0, characterized in that ring D is a 5- to 10-membered bicyclic heterocycle selected from a 5- to 10-membered fused heterocycle, a 5- to 10-membered bridging heterocycle, and a 5- to 10-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from halogen, -OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle.

56. Compound or salt, according to claim 0, characterized in that ring D is a 5- to 10-membered bicyclic heterocycle selected from a 5- to 10-membered bridging heterocycle and a 5- to 10-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from halogen, OR17, -N(R17)2, -C(O)R17, -NO2, -CN, C1-3 alkyl, C1-3 haloalkyl, and C3-6 carbocycle.

57. Compound or salt, according to claim 0, characterized in that ring D is a 5- to 10-membered bridging heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR17, C1-3 alkyl, and C1-3 haloalkyl.

58. Compound or salt, according to claim 0, characterized in that ring D is selected from 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, and 8-oxa-3-azabicyclo[3.2.1]octanyl, each of which is optionally substituted with one or more substituents independently selected from halogen, OR17, C1-3 alkyl, and C1-3 haloalkyl.

59. Compound or salt, according to claim 0, characterized by the fact that ring D is selected from ' , ' , θ 60. Compound or salt, according to claim 0, characterized in that ring D is a 5- to 10-membered spirocyclic heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR17, C1-3 alkyl, and C1-3 haloalkyl.

61. Compound or salt, according to claim 0, characterized in that ring D is selected from 2-oxa-6-azaespiro[3.3]heptanyl, 6-oxa-2-azaespiro[3.5]nonanyl, 7-oxa-2-azaespiro[3.5]nonanyl, 2-oxa-6azaespiro[3.4]octanyl, 4-oxa-7-azaespiro[2.5]octanyl, and 4-methyl-4,7diazaespiro[2.5]octanyl, each of which is optionally substituted with one or more substituents independently selected from halogen, OR17, C1-3 alkyl, and C1-3 haloalkyl.

62. Compound or salt, according to claim 0, characterized in that ring D is selected from 63. Compound or salt, according to claim 0, characterized in that ring D is a 5- to 10-membered fused heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR17, C1-3 alkyl, and C1-3 haloalkyl.

64. Compound or salt, according to claim 63, characterized by the fact that ring D is... (Petition 870250091144, dated 06 / 10 / 2025, pages 247 / 263 25 / 29) 65. Compound or salt, according to any one of claims 11 to 0, characterized in that ring D is selected 66. Compound or salt, according to any one of claims 11 to 0, characterized in that ring D is selected from Petition 870250091144, dated 06 / 10 / 2025, pp. 248 / 263 26 / 29 67. Compound or salt, according to any one of claims 11 to 0, characterized in that each R3 is independently selected in each occurrence of hydrogen, halogen, -OR16, -N(R16)2, -NO2, -CN, C1-3 alkyl, and C1-3 haloalkyl.

68. Compound or salt, according to claim 0, characterized in that each R3 is hydrogen.

69. Compound or salt, according to any one of claims 11 to 0, characterized in that R2 is hydrogen.

70. Compound or salt, according to any one of claims 11 to 0, characterized in that p is selected from 0, 1, 2, 3, and 4.

71. Compound or salt, according to any of the claims 11 to 0, characterized in that each R1 is independently selected in each occurrence of halogen, -OR14, -N(R14)2, -NO2, -CN, C1-6 alkyl, and C1-6 haloalkyl.

72. Compound or salt, according to claim 0, characterized in that each R1 is independently selected at each occurrence of halogen and -CF3.

73. Compound or salt, according to claim 11, characterized in that Formula (I) is selected from a compound in Table 1 or a pharmaceutically acceptable salt thereof.

74. Compound, characterized in that it is selected from the group consisting of: Petition 870250091144, dated 06 / 10 / 2025, pages 250 / 263 28 / 29 or a pharmaceutically acceptable salt of any of them.

75. Pharmaceutical composition, characterized in that it comprises a compound or salt, as defined in any one of claims 1 to 74, and a pharmaceutically acceptable excipient.

76. A method for modulating IL-17A in an individual in need thereof, characterized in that it comprises administering to the individual a compound or salt, as defined in any one of claims 1 to 0, or a pharmaceutical composition, as defined in claim 0.

77. A method for treating an inflammatory condition or disease, characterized in that it comprises administering to an individual in need thereof a compound or salt, as defined in any one of claims 1 to 0, or a pharmaceutical composition, as defined in claim 0.

78. Method, according to claim 0, characterized in that the inflammatory disease or condition is selected from platelet psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis and non-infectious uveitis.

79. Method of treating psoriasis, characterized by the fact that Petition 870250091144, dated 06 / 10 / 2025, pp. 251 / 263 29 / 29 comprises administering to an individual in need thereof a compound or salt, as defined in any of claims 1 to 0, or a pharmaceutical composition, as defined in claim 0.

80. A method for treating psoriatic arthritis, characterized in that it comprises administering to an individual in need thereof a compound or salt, as defined in any one of claims 1 to 0, or a pharmaceutical composition, as defined in claim 0.

81. A method for treating ankylosing spondylitis, characterized in that it comprises administering to an individual in need thereof a compound or salt, as defined in any one of claims 1 to 0, or a pharmaceutical composition, as defined in claim 0.

82. Use of a compound or salt as defined in any of claims 1 to 74, or of a pharmaceutical composition as defined in claim 75, characterized in that it is for the manufacture of a medicament for use in therapy.