Alpha-V-Beta 6 and Alpha-V-Beta 1 integrin inhibitors and their use

Abstract

Provided are alpha V beta6 and alpha V beta 1 integrin inhibitors, methods of making such alpha V beta6 and alpha V beta 1 integrin inhibitors, pharmaceutical compositions of alpha V beta6 and alpha V beta 1 integrin inhibitors and methods of treating and / or preventing various medical disorders in subjects in need of treatment by administration of alpha V beta6 and alpha V beta 1 integrin inhibitors.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims the benefits pursuant to U.S. Provisional Application 63 / 159,063 filed March 10, 2021, which are incorporated herein by reference in their entirety.

[0002] field Provided herein are αVβ6 and αVβ1 integrin inhibitors, methods for producing such αVβ6 and αVβ1 integrin inhibitors, pharmaceutical compositions of αVβ6 and αVβ1 integrin inhibitors, and methods for treating and / or preventing various medical disorders in subjects requiring treatment by administration of αVβ6 and αVβ1 integrin inhibitors. [Background technology]

[0003] background Integrins are α / β heterodimeric transmembrane proteins involved in cell adhesion to a wide range of extracellular matrix proteins, mediating cell-cell interactions, cell migration, cell proliferation, cell survival, and tissue integrity maintenance (Barczyk et al., Cell and Tissue Research 2010, 339, 269). Mammals have 24 α / β integrin heterodimers derived from combinations of 18 alpha and 8 beta subunits. Transforming growth factor β (TGFβ) plays a central role in driving several pathological processes underlying fibrosis, cell proliferation, and autoimmune diseases. Alpha V (αV) integrins, including αVβ1, αVβ3, αVβ5, αVβ6, and αVβ8, are involved in key pathways leading to the conversion of latent TGFβ into its active form (Henderson, NC; Sheppard, D. Biochim, Biophys. Acta 2013, 1832, 891). Therefore, the antagonistic effect of latent TGFβ on αV integrin-mediated activation provides a viable therapeutic approach to intervene in TGFβ-driven pathological conditions (Sheppard, D. Eur. Resp. Rev. 2008, 17, 157; Goodman, SL; Picard, M. Trends Pharmacol. Sciences 2012, 33(7), 405; Hinz, B., Nature Medicine 2013, 19(12), 1567; Pozzi, A.; Zent, ​​RJ Am. Soc. Nephrol. 2013, 24(7), 1034). The five αV integrins belong to a small subset (8 of 24) of integrins that recognize the arginine lysine aspartate (RGD) motif present in natural ligands such as fibronectin, vitronectin, and latent related peptide (LAP).

[0004] Integrins are expressed on the surface of most human cells. For example, αVβ6 and αVβ1 integrins are expressed at very low levels in epithelial cells in healthy tissue, but are significantly upregulated during inflammation and wound healing. Integrin pathology contributes to a diverse population of human diseases, including, for example, platelet disorders, atherosclerosis, cancer, osteoporosis, fibrosis, diabetic neuropathy of the kidney, macular degeneration, and various autoimmune and chronic inflammatory diseases. [Overview of the project] [Problems that the invention aims to solve]

[0005] Therefore, although αVβ6 and αVβ1 integrin inhibitors have been extensively tested, despite tremendous efforts, therapeutic success has been slow to be achieved. Accordingly, there is a need for αVβ6 and αVβ1 integrin inhibitors that, in some embodiments, can be delivered orally and can treat and / or prevent, for example, platelet disorders, atherosclerosis, cancer, osteoporosis, fibrosis, diabetic neuropathy of the kidney, macular degeneration, and various autoimmune and chronic inflammatory diseases. [Means for solving the problem]

[0006] overview In one aspect, formula (I) satisfies this and other requirements. [ka] [During the ceremony, Each R1 is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl or substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, halo, -C(O)NR8R9, -C(O)OR 10 、 -NR 11 C(O)OR 12 、 -NR 13 C(O)OR 14 、 -OC(O)OR 15 、 -CN, -CF3, -NR 16 SO2R 17 or -OR 18 ; m is 0, 1, 2 or 3; each R2 is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, halo, -C(O)NR 19 R 20, -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 n is 0, 1 or 2; each R3 is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, halo, -C(O)NR 30 R 31 , -C(O)OR 32 , -NR 33 C(O)OR 34 , -NR 35 C(O)OR 36 -OC(O)OR 37 -CN, -CF3, -NR 38 SO2R 39 OR 40And; q is 0, 1, 2 or 3; when q is 0, o is 0, 1 or 2; when q is 1, o is 0, 1, 2 or 3; when q is 2, o is 0, 1, 2, 3 or 4; when q is 3, o is 0, 1, 2, 3, 4 or 5; R4 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cyclo Substituting cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, -F, -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R4 and R5 are either -CN, -CF3, or R4 and R5, together with the atom to which they are bonded, form a C4-C8 cycloalkyl ring; E is -CH2- or -CH2Z-; Z is -NR 46 -, -S-, -SO2- or -O-; when E is -CH2-, D is -(CH2)2-, -(CH2)3-, -CH=CHCH2-, -C(O)-, -C≡CCH2-, phenyl, cyclohexyl or cyclopentyl; Z is NR 45 When D is -O-, D is -(CH2)2-, -(CH2)3-, -C(O)-, phenyl, cyclohexyl, or cyclopentyl; when Z is -SO2- or -S-, D is -(CH2)2-, -(CH2)3-, phenyl, cyclohexyl, or cyclopentyl; XY is -C(O)NR 46 -, -NR 47C(O)-, -C(O)O-, -CH2CH2-, -CH=CH-, -C≡C-, -NR 48 CH2-, -CH2NR 49 -, -O-CH2-, -CH2-O-, -SO2NR 50 -, -NR 51 SO2- or cyclopropyl; A is hydrogen, -OR 52 Alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted hetero -NR 53 R 54 , -OR 55 , -SR 56 or -SO2-R 57 And; R8~R 53 and R 58 ~R64 These are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, or substituted heteroarylalkynyl; 54 Alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, -C(O)R 58 , -C(O)OR 59 -C(O)NR 60 R 61 or -SO2R 62 and; R 55 ~R 57R5 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl or substituted heteroarylalkynyl; R5 is hydrogen or -F; R6 is hydrogen, -F or -OR 63 And R7 is hydrogen, -F or -OR 64 And; however, R4 is -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R5 is hydrogen when it is -CN; however, A is hydrogen, halo, or -OR when B is hydrogen or halo. 52 Rather; however, A is hydrogen, halo, or -OR 52 When B is not hydrogen or halo; however, if B is halo, -NR 53 R 54 , -OR 55 , -SR 56 or -SO2R 57 When R7 is hydrogen, R6 is -OR only when XY is -CH2CH2-, -CH=CH-, -C≡C- or cyclopropyl. 63 And; however, R6 is -OR 63 When A is -OR 52 [Not; and however, when R6 is -F, A is not -Cl, -Br, or -I.] Compounds thereof or pharmaceutically acceptable salts, hydrates, or solvates thereof are provided herein.

[0007] In other embodiments, derivatives comprising salts, esters, enol ethers, enol esters, solvates, hydrates, metabolites, and prodrugs of the compound of formula (I) described herein are provided. Further provided are pharmaceutical compositions comprising the compound of formula (I) provided herein and a pharmaceutically acceptable medium.

[0008] For example, methods for treating, preventing, or alleviating the symptoms of medical disorders such as platelet disorders, atherosclerosis, cancer, osteoporosis, fibrosis, diabetic neuropathy of the kidneys, macular degeneration, and various autoimmune diseases, as well as chronic inflammatory diseases, are provided herein. In carrying out this method, a therapeutically effective amount of the compound of formula (I) or a pharmaceutical composition thereof is administered to a patient having the disorder or condition.

[0009] A method for inhibiting αVβ6 integrin in a patient is described herein. In carrying out this method, a therapeutically effective amount of the compound of formula (I) or a pharmaceutical composition thereof is administered to the patient.

[0010] A method for inhibiting αVβ1 integrin in a patient is described herein. In carrying out this method, a therapeutically effective amount of the compound of formula (I) or a pharmaceutical composition thereof is administered to the patient.

[0011] A method for inhibiting TGFβ activation in cells is provided herein. In carrying out this method, an effective amount of the compound of formula (I) or a pharmaceutical composition thereof is administered to the cells.

[0012] In one aspect, formula (Ia) satisfies this and other requirements. [ka] {In the formula, q is 1, 2, or 3; R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11) 2, -C(O)N(R 11 ) 2, -C(O)OR 11 、=O, =S and -CN; m is selected from 0, 1, 2, 3, 4, 5 and 6; o is selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8; R 2 is independently in each case halogen, C 1-4 alkyl, C 1-4 haloalkyl, -OR 12 、-SR 12 、-N(R 12 ) 2, -CN and -NO2; n is 0, 1 or 2; R 4 and R 5 are each independently hydrogen, halogen, C 1-4 alkyl, C 1-4 haloalkyl, -OR 13 、-SR 13 、-N(R 13 ) 2 and -CN; or R 4 and R<00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2-, λ -C(R 15 )2O-, λ -SO2N(R 14 )-and λ -N(R 14 ) Selected from SO2-; Here, λ From XY [ka] It means a connection to; R 6 and R 7 Each of these is independently hydrogen, halogen, and C in each case. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 Selected from and -CN; A is (i) and (ii): (i) Hydrogen, halogens and -CN or A and R 6 They become one C 3-6 Forms a carbon ring or a 3- to 6-membered heteroring; (ii)-OR 17 , -SR 17 , -N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -S(O)R17 -S(O)2R 17 and -S(O)2N(R 17 )2; C 1-6 Alkyl (depending on the case) Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), -N3 and -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), substituted with one or more substituents independently selected from -N3 and -CN); and C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), -N3 and -CN; Depending on the situation, halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17)2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from; When A is selected from (ii), B is selected from (I) or When A is selected from (i), B is selected from (II): (I) Hydrogen, halogens and -CN or B and R 7 They become one C 3-6 Forms a carbon ring or a 3- to 6-membered heteroring; (II)-OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 and -S(O)2N(R 18 )2; C 1-6 Alkyl (depending on the case: Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3, -CN, C 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. Here, C 3-10 Carbon rings and 3-10 membered heterorings may contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18)2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), substituted with one or more substituents independently selected from -N3 and -CN); and C 3-12 Carbon rings and 3- to 12-membered heterorings [both depending on the case: Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3 and -CN; C 1-6 Alkyl (depending on the case: Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18, -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings [Substituted with one or more substituents independently selected from;] R 11 , R 12 , R 13 , R 14 and R 16 Each of them is independently hydrogen, C in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R 15 Independently, hydrogen, halogen, and C are used in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R 17 Each case is independent: hydrogen; Depending on the situation, halogen, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 -NO2, =O, =S, =N(R 21 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )C(O)OR 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(S)N(R 21 )2, -N(R 21 )S(O)2(R 21 ), -S(O)R 21 -S(O)2R 21 -S(O)2N(R 21 )2, -NO2, =O, =S, =N(R 21 ), C substituted with one or more substituents independently selected from -N3 and -CN 3-6 Carbon rings and 3- to 6-membered heterorings Selected from; R 18Each case is independent: hydrogen; C 1-6 Alkyl (depending on the case) Halogen, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 and -N(R 22 ) Substituted with one or more substituents independently selected from 2); and C 3-10 Carbon rings and 3- to 10-membered heterorings (both depending on the case): Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 , -N(R 22 )C(O)N(R 22 )2, -N(R 22 )C(S)N(R 22)2, -N(R 22 )S(O)2(R 22 ), -S(O)R 22 -S(O)2R 22 -S(O)2N(R 22 )2, -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 (Substituted with one or more substituents independently selected from the haloalkyl group.) Selected from; R 21 and R 22 Each is independent in its own case: hydrogen; Depending on the case, halogens, hydroxyls, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-4 Alkyl (where each C 3-6 Carbon rings and 3-6 membered heterorings are sometimes C 1-4 Alkyl, -N(R 23 )2 and -C(O)N(R 23 ) Substituted with one or more substituents independently selected from 2); and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 C substituted with one or more substituents independently selected from alkoxy and =O 3-6 Carbon rings and 3- to 12-membered heterorings Selected from; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups. Compounds or pharmaceutically acceptable salts thereof are provided.

[0013] In one embodiment, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable additive and a compound or salt of formula (Ia).

[0014] In one embodiment, the present invention provides a method for modulating alpha-V integrin in a subject requiring treatment, comprising administering to the subject a compound or salt of formula (Ia) or a pharmaceutical composition of formula (Ia).

[0015] In one embodiment, alpha-V integrin is alpha-V-beta-1 integrin.

[0016] In one embodiment, alpha-V integrin is alpha-V-beta-6 integrin.

[0017] In one embodiment, the present invention provides a method for treating a disease or condition, comprising administering a compound or salt of formula (Ia) or a pharmaceutical composition comprising a compound or salt of formula (Ia) to a subject in need thereof.

[0018] In one embodiment, the disease or condition is selected from idiopathic pulmonary fibrosis, systemic lupus erythematosus-associated interstitial lung disease, rheumatoid arthritis, diabetic nephropathy, focal segmental glomerulosclerosis, chronic kidney disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, solid tumors, hematological malignancies, organ transplantation, Alport syndrome, interstitial lung disease, radiation-induced fibrosis, bleomycin-induced fibrosis, asbestos-induced fibrosis, influenza-induced fibrosis, coagulation-induced fibrosis, vascular injury-induced fibrosis, aortic stenosis, and cardiac fibrosis. [Brief explanation of the drawing]

[0019] [Figure 1] Scheme 1, which shows the synthesis of intermediate 10, is shown.

[0020] [Figure 2] Scheme 2 shows the synthesis of the compound of formula (VII).

[0021] [Figure 3] Scheme 4 shows another synthesis of the compound of formula (VII).

[0022] [Figure 4] Scheme 6 shows the synthesis of the compound of formula (VIII).

[0023] [Figure 5] Scheme 10 shows another synthesis of the compound of formula (VIII).

[0024] [Figure 6] Scheme 12 shows the synthesis of the amide and sulfonamide of formula (VIII).

[0025] [Figure 7] Scheme 14 shows the synthesis of compounds in which the central piperidine ring is substituted and / or ED is not propyl. [Modes for carrying out the invention]

[0026] Inclusion by citation All publications, patents, and patent applications described herein are incorporated herein by reference to the same extent as each individual publication, patent, or patent application is specifically and individually incorporated herein by reference.

[0027] Detailed description of the invention definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this invention pertains. If multiple definitions exist for a single term, the definition in this section shall prevail unless otherwise specified.

[0028] As used herein and unless otherwise noted, the terms “about” and “approximately” when used in relation to the characteristics of a number or range of numbers may deviate to an extent that is reasonable to a person skilled in the art, while still describing certain properties. Specifically, when used in this context, the terms “about” and “approximately” indicate that a number or range of numbers may deviate from the stated value or range by 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1%.

[0029] "Alkyl" refers to a saturated, branched, or linear monovalent hydrocarbon radical derived from the removal of one hydrogen atom from a single carbon atom of a parent alkane, either by itself or as part of another substituent. Typical alkyl groups include, but are not limited to, methyl; ethyl; propyl (e.g., propan-1-yl, propan-2-yl); butyl (e.g., butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl, 2-methyl-propan-2-yl); and others. In some embodiments, an alkyl group consists of 1 to 20 carbon atoms (C1-C1). 20 Alkyl) is included. In other embodiments, the alkyl group is composed of 1 to 10 carbon atoms (C1-C 10 It contains alkyl. In yet another embodiment, the alkyl group contains 1 to 6 carbon atoms (C1-C6 alkyl).

[0030] "Alkenyl" refers to a branched or linear alkyl group having at least one carbon-carbon double bond, either by itself or as part of another substituent. The radical is derived from the removal of one hydrogen atom from a single carbon atom of the parent alkene. The group may be in either a cis or trans conformation with respect to the double bond. Typical alkenyl groups include, but are not limited to, ethenyl; propenyl such as prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl(allyl), prop-2-en-2-yl, cycloprop-1-en-1-yl; cycloprop-2-en-1-yl; butenyl such as but-1-en-1-yl, but-1-en-2-yl, 2-methylprop-1-en-1-yl, but-2-en-1-yl, but-2-en-1-yl, but-1,3-dien-1-yl, but-1,3-dien-2-yl, cyclobuto-1-en-1-yl, cyclobuto-1-en-3-yl, cyclobuta-1,3-dien-1-yl; and others. In one embodiment, the alkenyl group consists of 1 to 20 carbon atoms (C1-C 20 In other embodiments, the alkenyl group contains 1 to 10 carbon atoms (C1-C). 10 It contains an alkenyl group. In yet another embodiment, the alkenyl group contains 1 to 6 carbon atoms (C1-C6 alkenyl).

[0031] "Alkynyl" refers to a branched or linear alkyl group having at least one carbon-carbon triple bond, either by itself or as part of another substituent. The radical is derived from the removal of one hydrogen atom from a single carbon atom of the parent alkyne. Typical alkynyl groups include, but are not limited to, ethynyl; propynyl such as prop-1-in-1-yl, prop-2-in-1-yl; butynyl such as buto-1-in-1-yl, buto-1-in-3-yl, buto-3-in-1-yl; and so on. In some embodiments, the alkynyl group has 1 to 20 carbon atoms (C1-C 20 In other embodiments, the alkynyl group contains 1 to 10 carbon atoms (C1-C). 10It contains an alkynyl group. In yet another embodiment, the alkynyl group contains 1 to 6 carbon atoms (C1-C6 alkynyl).

[0032] "Aryl" means a monovalent aromatic hydrocarbon group derived from the removal of one hydrogen atom from a single carbon atom of an aromatic ring system, as defined herein, either by itself or as part of another substituent. Typical aryl groups include, but are not limited to, groups derived from acetantrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluorantene, fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene, indan, indene, naphthalene, octacene, octafen, octaene, ovalene, penta-2,4-diene, pentacene, pentalene, pentafen, perylene, phenalene, phenanthrene, picene, pleiaden, pyrene, pyranthrene, rubicene, triphenylene, and trinaphthalene. In some embodiments, the aryl group is derived from 6 to 20 carbon atoms (C6-C6). 20 In other embodiments, the aryl group contains 6 to 15 carbon atoms (C6-C). 15 In another embodiment, the aryl group contains 6 to 10 carbon atoms (C6-C). 10 Includes (Aryl).

[0033] "Arylalkyl" refers to a carbon atom, typically terminal or sp, as part of itself or other substituents. 3 An acyclic alkyl group is defined as one in which one hydrogen atom bonded to a carbon atom is substituted with an aryl group as described herein. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethane-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethane-1-yl, 2-naphthylethen-1-yl, naphthobenzyl, and 2-naphthophenylethane-1-yl. In one embodiment, the arylalkyl group is (C6-C 30 ) Arylalkyl, for example, the alkyl part of an arylalkyl group is (C1-C 10 ) is alkyl, and the aryl portion is (C6-C20 )aryl. In other embodiments, the arylalkyl group is (C6-C 20 ) Arylalkyl, for example, the alkyl portion of an arylalkyl group is (C1-C8) alkyl, and the aryl portion is (C6-C 12 )aryl. In yet another embodiment, the arylalkyl group is (C6-C 15 ) Arylalkyl, for example, the alkyl portion of an arylalkyl group is (C1-C5) alkyl, and the aryl portion is (C6-C 10 ) It is Ariel.

[0034] An "arylalkenyl" is an acyclic alkenyl group in which one of the hydrogen atoms bonded to a carbon atom is replaced by an aryl group as defined herein, either by itself or as part of another substituent. In one embodiment, the arylalkenyl group is (C6-C 30 ) Aryl alkenyls, for example, the alkenyl portion of the aryl alkenyl group is (C1-C 10 ) is an alkenyl, and the aryl portion is (C6-C 20 ) is aryl. In other embodiments, the arylalkenyl group is (C6-C 20 ) Aryl alkenyls, for example, the alkenyl portion of the aryl alkenyl group is (C1-C8) alkenyl, and the aryl portion is (C6-C 12 )aryl. In yet another embodiment, the arylalkenyl group is (C6-C 15 ) Aryl alkenyls, for example, the alkenyl portion of the aryl alkenyl group is (C1-C5) alkenyl, and the aryl portion is (C6-C 10 ) It is Ariel.

[0035] "Arylalkynyl" refers to an acyclic alkynyl group in which one of the hydrogen atoms bonded to a carbon atom is replaced by an aryl group as defined herein, either by itself or as part of another substituent. In one embodiment, the arylalkynyl group is (C6-C 30 ) Arylalkynyl, for example, the alkynyl portion of the arylalkynyl group is (C1-C 10) is an alkynyl, and the aryl portion is (C6-C 20 ) is aryl. In another embodiment, the arylalkynyl group is (C6-C 20 ) Arylalkynyl, for example, the alkynyl portion of the arylalkynyl group is (C1-C8)alkynyl, and the aryl portion is (C6-C 12 ) is aryl. In yet another embodiment, the arylalkynyl group is (C6-C 15 ) Arylalkynyl, for example, the alkynyl portion of the arylalkynyl group is (C1-C5)alkynyl, and the aryl portion is (C6-C 10 ) It is Ariel.

[0036] As used herein, "carbocyclic ring" refers to a ring in which each atom is carbon, and which can be saturated, unsaturated, or aromatic. Carbocyclic rings include 3- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings. Each ring in a bicyclic carbocyclic ring may be selected from saturated, unsaturated, and aromatic rings. Bicyclic carbocyclic rings can be condensed, bridged, or spirocyclic systems. In some embodiments, the carbocyclic ring is aryl. In some embodiments, the carbocyclic ring is cycloalkyl. In some embodiments, the carbocyclic ring is cycloalkenyl. In exemplary embodiments, an aromatic ring, e.g., phenyl, may be condensed with a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of a carbocyclic ring, as far as valence allows. Examples of carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The carbon ring may be substituted with one or more substituents, such as those listed here.

[0037] "Cycloalkyl" refers to a saturated cyclic monovalent hydrocarbon radical derived from the removal of one hydrogen atom from a single carbon atom of a parent cycloalkane, either by itself or as part of another substituent. Typical cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentylcyclopentenyl, etc. In some embodiments, a cycloalkyl group consists of 3 to 15 carbon atoms (C3-C3). 15It contains a cycloalkyl group. In other embodiments, the cycloalkyl group has 3 to 10 carbon atoms (C3-C3). 10 This includes cycloalkyl groups. In further embodiments, the cycloalkyl group includes 3 to 8 carbon atoms (C3-C8 cycloalkyl). The term "cycloalkyl" also includes single radicals and polycyclic hydrocarbon ring systems having 5 to 15 carbon atoms. Examples of polycyclic cycloalkyl rings include crosslinked, condensed, and spirocycloalkyl ring systems, for example, norbolonyl, pinyl, and adamantyl.

[0038] A "cycloalkenyl" is an unsaturated cyclic monovalent hydrocarbon radical derived from the removal of one hydrogen atom from a single carbon atom of a parent cycloalkene, either by itself or as part of another substituent. Typical cycloalkenyl groups include, but are not limited to, cyclopropene, cyclobutene, cyclopentene, etc. In some embodiments, the cycloalkenyl group consists of 3 to 15 carbon atoms (C3-C3). 15 It contains a cycloalkenyl group. In other embodiments, the cycloalkenyl group has 3 to 10 carbon atoms (C3-C3). 10 This includes cycloalkenyl groups. In other embodiments, the cycloalkenyl group includes 3 to 8 carbon atoms (C3-C8 cycloalkenyl). The term "cycloalkenyl" also includes single radicals and polycyclic hydrocarbon ring systems having 5 to 15 carbon atoms and an alkenyl group.

[0039] A "cycloheteroalkyl" is a cycloalkyl group in which one or more carbon atoms (and optionally any associated hydrogen atoms) are substituted, either by themselves or as part of other substituents, with the same or different heteroatoms or heteroatomic groups as defined below. In some embodiments, a cycloheteroalkyl group has 3 to 15 carbon atoms (C3-C3). 15 It contains a cycloheteralkyl group. In other embodiments, the cycloheteralkyl group has 3 to 10 carbon atoms (C3-C3). 10This includes cycloheteralkyls. In further embodiments, the cycloheteralkyls include 3 to 8 carbon atoms (C3-C8 cycloheteralkyls). The term "cycloheteralkyl" also includes single radicals and polycyclic hydrocarbon ring systems having at least one heteroatom, having 5 to 15 carbon atoms.

[0040] A "cycloheteralkenyl" is a cycloalkenyl group in which one or more carbon atoms (and optionally any associated hydrogen atoms) are substituted, independently of each other, with the same or different heteroatoms or heteroatomic groups as defined below for "heteralkenyl". In some embodiments, the cycloheteralkenyl group has 3 to 15 carbon atoms (C3-C3). 15 It contains a cycloheteralkyl. In other embodiments, the cycloheteralkyl has 3 to 10 carbon atoms (C3-C3). 10 This includes cycloheteralkyls. In further embodiments, the cycloheteralkyl comprises 3 to 8 carbon atoms (C3-C8 cycloheteralkyl). The term "cycloheteralkyl" also includes a single radical and a polycyclic hydrocarbon ring system having at least one heteroatom and one alkenyl group, having 5 to 15 carbon atoms.

[0041] "Compound" means the compound contained in the structural formulas disclosed herein, and includes all specific compounds in these formulas whose structures are specifically disclosed herein. Compounds are identified by their chemical structure and / or chemical name. The compounds described herein may contain one or more chiral centers and / or double bonds, and therefore may exist as stereoisomers such as double bond isomers (i.e., geometric isomers), enantiomers, or diastereomers. Accordingly, the chemical structures described herein include the stereoisomerically pure form described in the structure (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure). The chemical structures described herein also include enantiomers and stereoisomeric derivatives of the compounds described. Enantiomers and stereoisomeric mixtures can be separated into component enantiomers or stereoisomers using separation techniques or chiral synthesis techniques well known to those skilled in the art. Compounds may also exist in polytautomeric forms, including enol forms, keto forms, and mixtures thereof. Accordingly, the chemical structures described herein include all possible tautomeric forms of the compounds described. The compounds described herein include isotope-labeled compounds in which one or more atoms have atomic masses different from those commonly found in nature. Examples of isotopes that may be incorporated into the compounds disclosed herein are: 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 18 O, 17 This includes, but is not limited to, O. Compounds can exist in solvated forms, including unsolvated and hydrated forms. Generally, compounds can be hydrated or solvated. Some compounds can exist in multiple crystalline or amorphous forms. Generally, all physical forms are intended to be equivalent for the applications contemplated herein and to be within the scope of the invention. Furthermore, when a substructure of a compound is described, a dashed line should be understood to indicate the bond point of that substructure to the rest of the molecule.

[0042] "Halo" refers to a radical -F, -Cl, -Br, or -I, either by itself or as part of another substituent.

[0043] A "heteroalkyl" is an alkyl group in which one or more carbon atoms (and optionally any associated hydrogen atoms) are substituted, independently of each other, by the same or different heteroatoms or heteroatomic groups, either by themselves or as part of other substituents. Typical heteroatoms or heteroatomic groups that can substitute carbon atoms include, but are not limited to, -O-, -S-, -N-, -Si-, -NH-, -S(O)-, -S(O)2-, -S(O)NH-, -S(O)2NH-, and combinations thereof. Heteroatoms or heteroatomic groups can be located at any internal position of the alkyl group. Typical heteroatomic groups that can be included in these groups are -O-, -S-, -OO-, -SS-, -OS-, -NR 501 R 502 ,=NN=,-N=N-,-N=N-NR 503 R 504 ,-PR 505 -, -P(O)2-, -POR 506 -, -OP(O)2-, -SO-, -SO2-, -SnR 507 R 508 This includes, but is not limited to, R 501 , R 502 , R 503 , R 504 , R 505 , R 506 , R 507 and R 508 These are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl and their substituted counterparts.

[0044] A "heteroalkenyl" is an alkenyl group in which one or more carbon atoms (and optionally any associated hydrogen atoms) are each independently substituted with the same or different heteroatoms or heteroatomic groups. Typical heteroatoms or heteroatomic groups that can substitute carbon atoms include, but are not limited to, -O-, -S-, -N-, -Si-, -NH-, -S(O)-, -S(O)2-, -S(O)NH-, -S(O)2NH-, etc., and combinations thereof. Heteroatoms or heteroatomic groups can be located at any internal position of the alkenyl group. Typical heteroatomic groups that can be included in these groups are -O-, -S-, -OO-, -SS-, -OS-, -NR 509 R 510 ,=NN=,-N=N-,-N=N-NR 511 R 512 ,-PR 514 -, -P(O)2-, -POR 514 -, -OP(O)2-, -SO-, -SO2-, -SnR 515 R 516 This includes, but is not limited to, R 509 , R 510 , R 511 , R 512 , R 513 , R 514 , R 515 and R 516 These are independently hydrogen, alkyl, aryl, substituted aryl, heteroalkyl, heteroaryl, or substituted heteroaryl.

[0045] A "heteroalkynyl" is an alkynyl group in which one or more carbon atoms (and optionally any associated hydrogen atoms) are substituted, independently of each other, with the same or different heteroatoms or heteroatomic groups, either by themselves or as part of other substituents. Typical heteroatoms or heteroatomic groups that can substitute carbon atoms include, but are not limited to, -O-, -S-, -N-, -Si-, -NH-, -S(O)-, -S(O)2-, -S(O)NH-, -S(O)2NH-, and combinations thereof. Heteroatoms or heteroatomic groups can be located at any internal position of the alkynyl group. Typical heteroatomic groups that can be included in these groups are -O-, -S-, -OO-, -SS-, -OS-, -NR 517 R 518 ,=NN=,-N=N-,-N=N-NR 519 R 520 ,-PR 521 -, -P(O)2-, -POR 52 2 -, -OP(O)2-, -SO-, -SO2-, -SnR 523 R 524 This includes, but is not limited to, R 517 , R 518 , R 519 , R 520 , R 521 , R 522 , R 523 and R 524 These are independently hydrogen, alkyl, aryl, substituted aryl, heteroalkyl, heteroaryl, or substituted heteroaryl.

[0046] A "heteroaryl" is a monovalent heteroaromatic radical derived from the removal of a single hydrogen atom from a single atom of a parent heteroaromatic ring system, as defined above, either by itself or as part of another substituent. Typical heteroaryl groups include, but are not limited to, groups derived from acridine, β-carbolin, chroman, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indidine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthoridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, quinazoline, quinoline, quinolidine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, and xanthene. In one embodiment, the heteroaryl group comprises 5 to 20 ring atoms (5 to 20-membered heteroaryl). In another embodiment, the heteroaryl group comprises 5 to 10 ring atoms (5 to 10-membered heteroaryl). Examples of heteroaryl groups include those derived from furan, thiophene, pyrrole, benzothiophene, benzofuran, benzimidazole, indole, pyridine, pyrazole, quinoline, imidazole, oxazole, isoxazole, and pyrazine.

[0047] "Heteroarylalkyl" is a group of atoms, either themselves or as part of other substituents, that consist of carbon atoms, typically terminal or sp. 3 An acyclic alkyl group is defined as one of the hydrogen atoms bonded to a carbon atom that is replaced by a heteroaryl group. In one embodiment, the heteroarylalkyl group is a 6-21 member heteroarylalkyl group, for example, the alkyl portion of the heteroarylalkyl group is (C1-C6) alkyl and the heteroaryl portion is a 5-15 member heteroaryl group. In another embodiment, the heteroarylalkyl group is a 6-13 member heteroarylalkyl group, for example, the heteroalkyl portion is (C1-C3) alkyl and the heteroaryl portion is a 5-10 member heteroaryl group.

[0048] A "heteroarylalkenyl" is an acyclic alkenyl group in which, either itself or as part of another substituent, one of the hydrogen atoms bonded to a carbon atom is replaced by a heteroaryl group. In one embodiment, the heteroarylalkenyl group is a 5-21 member heteroarylalkenyl, for example, the alkenyl portion of the heteroarylalkenyl is a (C2-C6) alkenyl and the heteroaryl portion is a 3-15 member heteroaryl. In another embodiment, the heteroarylalkenyl is a 6-13 member heteroarylalkenyl, for example, the alkenyl portion is a (C3) alkenyl and the heteroaryl portion is a 3-10 member heteroaryl.

[0049] A "heteroarylalkynyl" is an acyclic alkynyl group in which, either itself or as part of another substituent, one hydrogen atom bonded to a carbon atom is replaced by a heteroaryl group. In one embodiment, the heteroarylalkynyl group is a 5-21 member heteroarylalkynyl, for example, the alkynyl portion of the heteroarylalkynyl is a (C2-C6) alkynyl and the heteroaryl portion is a 3-15 member heteroaryl. In another embodiment, the heteroarylalkynyl is a 6-13 member heteroarylalkynyl, for example, the alkynyl portion is a (C3) alkynyl and the heteroaryl portion is a 3-10 member heteroaryl.

[0050] As used herein, "heterocycle" refers to a saturated, unsaturated, non-aromatic, or aromatic ring containing one or more heteroatoms. Heteroatoms include N, O, Si, P, B, and S atoms. Examples of heterocycles include 3- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings. Each ring in a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocycle may be bonded to the rest of the molecule via any atom of the heterocycle, such as a carbon or nitrogen atom of the heterocycle, as valence-permissible. In some embodiments, the heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl. Examples of heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl. Bicyclic heterocycles may be condensed, crosslinked, or spirocycle systems. In exemplary embodiments, a heterocycle, e.g., pyridyl, may be condensed to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Heterocycles may optionally be substituted with one or more substituents, such as those described herein.

[0051] "Hydrate" refers to the incorporation of water into the crystal lattice of the compounds described herein in stoichiometric ratios, resulting in the formation of adducts. The hydrated forms of the compounds described herein are also considered to be disclosed herein. Methods for producing hydrates include, but are not limited to, storage in a water vapor atmosphere, water-containing dosage forms, or common pharmaceutical processing steps such as crystallization (i.e., from water or a mixed aqueous solvent), freeze-drying, wet granulation, aqueous film coating, or spray-drying. Hydrates may be formed under certain conditions from crystalline solvates by exposure to water vapor or suspension of anhydrous substances in water. Hydrates may also crystallize into more than one form, resulting in hydrate polymorphisms. See, for example, (Guillory, K., Chapter 5, pp. 202205 in Polymorphism in Pharmaceutical Solids, (Brittain, H. ed.), Marcel Dekker, Inc., New York, NY, 1999). The above method for producing hydrates is well within the realm of those skilled in the art, entirely conventional, and requires no experiments beyond those typical in the art. Hydrates can be characterized and / or analyzed by methods well known to those skilled in the art, such as single-crystal X-ray diffraction, X-ray powder diffraction, polarized optical microscopy, thermal microscopy, thermogravimetric analysis, differential thermal analysis, differential scanning calorimetry, IR spectroscopy, Raman spectroscopy, and NMR spectroscopy. (Brittain, H., Chapter 6, pp. 205-208 in Polymorphism in Pharmaceutical Solids, (Brittain, H. ed.), Marcel Dekker, Inc. New York, 1999). Furthermore, many commercial companies, such as HOLODIAG, Pharmaparc II, Voie de l'Innovation, 27 100 Val de Reuil, France (http: / / www.holodiag.com), routinely offer services including the preparation and / or characterization of hydrates.

[0052] A "philophilic aromatic ring system" refers to an unsaturated cyclic or polycyclic ring system that has a conjugated π-electron system. Specifically, the definition of a "philophilic aromatic ring system" includes, for example, fluorene, indane, indene, and phenalene, which are condensed ring systems in which one or more rings are aromatic and one or more rings are saturated or unsaturated. Typical aromatic ring systems include, but are not limited to, acetantrylene, acetanaphthylene, acetphenantrylene, anthracene, azulene, benzene, chrysene, coronene, fluorantene, fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octafen, octalen, ovalen, penta-2,4-diene, pentacene, pentalene, pentafen, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, and trinaphthalene. Saturated ring systems may contain one or more heteroatoms.

[0053] A "hetero-aromatic ring system" is a ring system in which one or more carbon atoms (and optionally any associated hydrogen atoms) are independently substituted by the same or different heteroatoms. Typical heteroatoms that substitute carbon atoms include, but are not limited to, N, P, O, S, and Si. Specific examples of ring systems specifically included in the definition of "hetero-aromatic ring systems" are benzodioxane, benzofuran, chroman, chromene, indole, indoline, and xanthene, which are fused ring systems in which one or more rings are aromatic and one or more rings are saturated or unsaturated. Typical hetero-aromatic ring systems include, but are not limited to, arsindol, carbazole, β-carbolin, chroman, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indoridine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthoridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, quinazoline, quinoline, quinoridine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, and xanthene. Saturated ring systems may contain one or more heteroatoms.

[0054] "Pharmacologically acceptable salt" refers to a salt of a compound that has the desired pharmacological activity of the parent compound. Such salts are formed (1) with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or with acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4 (2) Acid addition salts formed with organic acids such as -methylbicyclo[2.2.2]-octo-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and muconic acid; or (2) formed when an acidic proton present in the parent compound is substituted with a metal ion, such as an alkali metal ion, an alkaline earth ion, or an aluminum ion; or include base addition salts that coordinate with organic bases such as ethanolamine, diethanolamine, triethanolamine, and N-methylglucamine.

[0055] "Prevention" or "prevention" refers to a reduction in the risk of acquiring a disease or disability (i.e., prevention of the progression of at least one clinical symptom of a disease in a patient who is exposed to or predisposed to the disease but has not yet experienced or shown symptoms of the disease). An application for the treatment of preventing or preventing a disease or disability is known as 'prevention'. In one embodiment, the compound provided herein provides excellent prevention due to its low long-term side effects over a long period.

[0056] A "protecting group" is a group of atoms that, when bonded to a reactive functional group in a molecule, masks, reduces, or inhibits the reactivity of that functional group in chemical synthesis. An example of a protecting group is found in Green et al., “Protective Groups in Organic Chemistry”, (Wiley, 2 nd This can be seen in (ed. 1991) and Harrison et al., “Compendium of Synthetic Organic Methods”, Vols. 18 (John Wiley and Sons, 1971-1996). Representative amino protecting groups include, but are not limited to, formyl, acetyl, trifluoroacetyl, benzyl, benzyloxycarbonyl ("CBZ"), tert-butoxycarbonyl ("Boc"), trimethylsilyl ("TMS"), 2-trimethylsilyl-ethanesulfonyl ("SES"), trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl ("FMOC"), and nitroveratryloxycarbonyl ("NVOC"). Representative hydroxy protecting groups include, but are not limited to, those in which the hydroxyl group is acylated or alkylated, such as benzyl and trityl ethers and alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers and allyl ethers.

[0057] A “solvate” refers to a solvent in the crystal lattice of the compound described herein in stoichiometric ratios that results in the formation of an adduct. Furthermore, the compounds described herein may exist in unsolvated forms and in solvated forms with pharmaceutically acceptable solvents such as water and ethanol. The solvated forms of the compounds shown herein are also considered to be disclosed herein. Methods for producing solvates include, but are not limited to, storage in a solvent-containing atmosphere, solvent-containing dosage forms, or routine pharmaceutical processing steps such as crystallization (i.e., from a solvent or mixed solvent) and vapor diffusion. Solvates may be formed, under certain circumstances, from other crystalline solvates or hydrates, by exposure to a solvent or suspension of a substance in a solvent. Solvates may also crystallize into more than one form, resulting in solvate polymorphism. See, for example, (Guillory, K., Chapter 5, pp. 205-208 in Polymorphism in Pharmaceutical Solids, (Brittain, H. ed.), Marcel Dekker, Inc., New York, NY, 1999). The above method for preparing solvates is well within the realm of the art, entirely conventional, and requires no experiments beyond those routine in the art. Solvates can be characterized and / or analyzed by methods well known to those skilled in the art, such as single-crystal X-ray diffraction, X-ray powder diffraction, polarized optical microscopy, thermal microscopy, thermogravimetric analysis, differential thermal analysis, differential scanning calorimetry, IR spectroscopy, Raman spectroscopy, and NMR spectroscopy. (Brittain, H., Chapter 6, pp. 205208 in Polymorphism in Pharmaceutical Solids, (Brittain, H. ed.), Marcel Dekker, Inc. New York, 1999). Furthermore, many commercial companies, such as HOLODIAG, Pharmaparc II, Voie de l'Innovation, 27 100 Val de Reuil, France (http: / / www.holodiag.com), routinely offer services including the preparation and / or characterization of solvates.

[0058] "Substitution" refers to the modification of a particular group or radical in which one or more hydrogen atoms of that particular group or radical are each independently substituted with the same or different substituents. Substituents useful for substituting saturated carbon atoms in the particular group or radical include R a Hello, -O - ,=O,-OR b , -SR b , -S - ,=S,-NR c R c ,=NR b 、=N-OR b , trihalomethyl, -CF3, -CN, -OCN, -SCN, -NO, -NO2, -N-OR b , -N-NR c R c , -NR b S(O)2R b , =N2, -N3, -S(O)2R b -S(O)2NR b R b -S(O)2O - -S(O)2OR b -OS(O)2R b -OS(O)2O - -OS(O)2OR b -OS(O)2NR c NR c ,-P(O)(O - )2, -P(O)(OR b )(O - ), -P(O)(OR b )(OR b ), -C(O)R b -C(O)NR b -OR b ,-C(S)R b -C(NR b )R b ,-C(O)O - , -C(O)OR b , -C(S)OR b -C(O)NR c R c -C(NR b )NR c R c -OC(O)R b,-OC(S)R b ,-OC(O)O - -OC(O)OR b -OC(O)NR c R c -OC(NCN)NR c R c , -OC(S)OR b , -NR b C(O)R b , -NR b C(S)R b , -NR b C(O)O - , -NR b C(O)OR b , -NR b C(NCN)OR b , -NR b S(O)2NR c R c , -NR b C(S)OR b , -NR b C(O)NR c R c , -NR b C(S)NR c R c , -NR b C(S)NR b C(O)R a , -NR b S(O)2OR b , -NR b S(O)2R b , -NR b C(NCN)NR c R c , -NR b C(NR b )R b and -NR b C(NR b )NR c R c This includes, where each R aEach R is independently an aryl, substituted aryl, aryl alkenyl, substituted aryl alkenyl, aryl alkynyl, substituted aryl alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroaryl alkynyl or substituted heteroaryl alkynyl; each R b R is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl or substituted heteroarylalkynyl; and each R c R is independent b or two R c These groups, together with the nitrogen atom to which they are bonded, form a cycloheteralkenyl condensed with a 4-membered, 5-membered, 6-membered, or 7-membered cycloheteralalkyl, substituted cycloheteralalkyl, cycloheteralkenyl, substituted cycloheteralkenyl, or cycloheteralalkyl or aryl group, which may optionally contain 1 to 4 further identical or different heteroatoms selected from the group consisting of O, N, and S. A specific example is -NR c R cThis is intended to include -NH2, -NH-alkyl, N-alkenyl, N-pyrrolidinyl, and N-morpholinyl. In other embodiments, substituents useful for substituting saturated carbon atoms in the particular group or radical are R a Hello, -OR b , -NR c R c , trihalomethyl, =N-OR b -CN, -NR b S(O)2R b , -C(O)R b , -C(O)OR b -C(O)NR c R c -OC(O)R b -OC(O)OR b -S(O)2R b -S(O)2NR c NR c -OC(O)NR c R c and -NR b C(O)OR b Including, here, R a , R b and R c This is as defined above.

[0059] Substituents useful for substituting unsaturated carbon atoms in the particular group or radical are -R a Hello, -O - , -OR b , -SR b , -S - , -NR c R c Trihalomethyl, -CF3, -CN, -OCN, -SCN, -NO, -NO2, -N3, -S(O)2O - -S(O)2OR b -OS(O)2R b -OS(O)2OR b -OS(O)2O - ,-P(O)(O - )2, -P(O)(OR b )(O - ), -P(O)(OR b )(OR b ), -C(O)Rb ,-C(S)R b -C(NR b )R b ,-C(O)O - , -C(O)OR b , -C(S)OR b -C(O)NR c R c -C(NR b )NR c R c -OC(O)R b ,-OC(S)R b ,-OC(O)O - -OC(O)OR b , -OC(S)OR b -OC(O)NR c R c -OS(O)2NR c NR c , -NR b C(O)R b , -NR b C(S)R b , -NR b C(O)O - , -NR b C(O)OR b , -NR b S(O)2OR a , -NR b S(O)2R a , -NR b C(S)OR b , -NR b C(O)NR c R c , -NR b C(NR b )R b and -NR b C(NR b )NR c R c Including, here, R a , R b and R c This is as previously defined. In other embodiments, substituents useful for substituting an unsaturated carbon atom in the particular group or radical are -R a Hello, -OR b , -SR b , -NR c R c, trihalomethyl, -CN, -S(O)2OR b , -C(O)R b , -C(O)OR b -C(O)NR c R c -OC(O)R b -OC(O)OR b -S(O)2NR c NR c , -NR b C(O)R b and -NR b C(O)OR b Including, here, R a , R b and R c This is as defined earlier.

[0060] Substituents useful for substituting nitrogen atoms in heteroalkyl and cycloheteralkyl groups are -R a , -O - , -OR b , -SR b , -S - , -NR c R c , trihalomethyl, -CF3, -CN, -NO, -NO2, -S(O)2R b -S(O)2O - -S(O)2OR b -OS(O)2R b -OS(O)2O - -OS(O)2OR b ,-P(O)(O - )2, -P(O)(OR b )(O - ), -P(O)(OR b )(OR b ), -C(O)R b ,-C(S)R b -C(NR b )R b , -C(O)OR b , -C(S)OR b -C(O)NR c R c -C(NR b )NR c R c -OC(O)R b,-OC(S)R b -OC(O)OR b , -OC(S)OR b , -NR b C(O)R b , -NR b C(S)R b , -NR b C(O)OR b , -NR b C(S)OR b , -NR b C(O)NR c R c , -NR b C(NR b )R b and -NR b C(NR b )NR c R c Including, here, R a , R b and R c The substituents are as previously defined in the first embodiment of the "substitution" described above. In one embodiment, substituents useful for substituting nitrogen atoms in heteroalkyl, heteroalkenyl, cycloheteralkyl, and cycloheteralkenyl groups are R a , -OR b , -NR c R c , trihalomethyl, -CN, -S(O)2OR b -OS(O)2R b -OS(O)2OR b , -C(O)R b -C(NR b )R b , -C(O)OR b -C(O)NR c R c -OC(O)R b -OC(O)OR b -OS(O)2NR c NR c , -NR b C(O)R b and -NR b C(O)OR b Including, here, R a , R b and R cis as previously defined in the first embodiment of the above "substitution".

[0061] In one embodiment, substituents useful for substitution of saturated carbon atoms in the particular group or radical are R a , halo, -OR b , -NR c R c , trihalomethyl, =N-OR b , -CN, -NR b S(O)2R b , -C(O)R b , -C(O)OR b , -C(O)NR c R c , -OC(O)R b , -OC(O)OR b , -S(O)2R b , -S(O)2NR c NR c , -OC(O)NR c R c and -NR b C(O)OR b and substituents useful for substitution of unsaturated carbon atoms in the particular group or radical are -R a , halo, -OR b , -SR b , -NR c R c , trihalomethyl, -CN, -S(O)2OR b , -C(O)R b , -C(O)OR b , -C(O)NR c R c , -OC(O)R b , -OC(O)OR b , -S(O)2NR c NR c , -NR b C(O)R b and -NR b C(O)OR b and substituents useful for substitution of nitrogen atoms in heteroalkenyl, cycloheteroalkyl or cycloheteroalkenyl groups are R a , -OR b , -NR c Rc , trihalomethyl, -CN, -S(O)2OR b -OS(O)2R b -OS(O)2OR b , -C(O)R b -C(NR b )R b , -C(O)OR b -C(O)NR c R c -OC(O)R b -OC(O)OR b -OS(O)2NR c NR c , -NR b C(O)R b and -NR b C(O)OR b This includes, where each R a R is independently an aryl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, or heteroarylalkynyl; b R is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, substituted heteroalkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, or heteroarylalkynyl, and each R c R is independent b or two R c These atoms, together with the nitrogen atom to which they are bonded, form a 4-membered, 5-membered, 6-membered, or 7-membered cycloheteralkyl or cycloheteralkenyl ring.

[0062] In one embodiment, the substituent used to substitute a particular group may be further substituted with one or more identical or different groups selected from the various groups typically identified above.

[0063] The terms "subject," "individual," or "patient" are used interchangeably here and refer to vertebrates, preferably mammals. Mammals include, but are not limited to, mice, rodents, apes, humans, livestock, sports animals, and pets.

[0064] In some embodiments, “to treat” or “treatment” any disease or disorder means improvement of the disease or disorder (i.e., stopping or reducing the progression of at least one of the disease or its clinical symptoms). Treatment may also be considered to include preemptive or prophylactic administration for improvement, stopping or preventing the progression of at least one of the disease or clinical symptoms. In further characteristics, treatment reduces the possibility of long-term side effects over several years. In other embodiments, “to treat” or “treatment” means improvement of at least one physical parameter that may not be recognizable by the patient. In yet another embodiment, “to treat” or “treatment” means prevention of the disease or disorder by physical means (e.g., stabilization of recognizable symptoms), physiological means (e.g., stabilization of physical parameters), or both. In yet another embodiment, “to treat” or “treatment” means delaying the onset of the disease or disorder.

[0065] The "therapeutic dose" refers to the amount of compound that is sufficient to treat a disease when administered to a patient for that purpose. The "therapeutic dose" varies depending on the compound, the disease and its severity, and the age, weight, absorption, distribution, metabolism, and excretion of the patient being treated.

[0066] The term "medium" refers to a diluent, additive, or carrier along with which the compound is administered to the target. In some embodiments, the medium is pharmaceutically acceptable.

[0067] compound The formula provided is (I) [ka] [During the ceremony, Each R1 is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, or substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, halo, -C(O)NR8R9, -C(O)OR 10 , -NR 11 C(O)OR 12 , -NR 13 C(O)OR 14 -OC(O)OR 15 -CN, -CF3, -NR 16 SO2R 17 OR 18 m is 0, 1, 2 or 3; each R2 is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, halo, -C(O)NR 19 R 20、 -C(O)OR 21 、 -NR 22 C(O)OR 23 、 -NR 24 C(O)OR 25 、 -OC(O)OR 26 、 -CN, -CF3, -NR 27 SO2R 28 or -OR 29 and n is 0, 1 or 2; each R3 is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, halo, -C(O)NR 30 R 31 、 -C(O)OR 32 、 -NR 33 C(O)OR 34 、 -NR 35 C(O)OR 36 、 -OC(O)OR 37 、 -CN, -CF3, -NR 38 SO2R 39 or -OR 40And; q is 0, 1, 2 or 3; when q is 0, o is 0, 1 or 2; when q is 1, o is 0, 1, 2 or 3; when q is 2, o is 0, 1, 2, 3 or 4; when q is 3, o is 0, 1, 2, 3, 4 or 5; R4 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cyclo Substituting cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, -F, -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R4 and R5 are either -CN, -CF3, or R4 and R5, together with the atom to which they are bonded, form a C4-C8 cycloalkyl ring; E is -CH2- or -CH2Z-; Z is -NR 46 -, -S-, -SO2- or -O-; when E is -CH2-, D is -(CH2)2-, -(CH2)3-, -CH=CHCH2-, -C(O)-, -C≡CCH2-, phenyl, cyclohexyl or cyclopentyl; Z is NR 45 When D is -O-, D is -(CH2)2-, -(CH2)3-, -C(O)-, phenyl, cyclohexyl, or cyclopentyl; when Z is -SO2- or -S-, D is -(CH2)2-, -(CH2)3-, phenyl, cyclohexyl, or cyclopentyl; XY is -C(O)NR 46 -, -NR 47C(O)-, -C(O)O-, -CH2CH2-, -CH=CH-, -C≡C-, -NR 48 CH2-, -CH2NR 49 -, -O-CH2-, -CH2-O-, -SO2NR 50 -, -NR 51 SO2- or cyclopropyl; A is hydrogen, -OR 52 Alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted hetero -NR 53 R 54 , -OR 55 , -SR 56 or -SO2-R 57 And; R8~R 53 and R 58 ~R64 These are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, or substituted heteroarylalkynyl; 54 Alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl, substituted heteroarylalkynyl, -C(O)R 58 , -C(O)OR 59 -C(O)NR 60 R 61 or -SO2R 62 and; R 55 ~R 57R5 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, substituted heteroalkenyl, heteroalkynyl, substituted heteroalkynyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, heteroarylalkynyl or substituted heteroarylalkynyl; R5 is hydrogen or -F; R6 is hydrogen, -F or -OR 63 And R7 is hydrogen, -F or -OR 64 And; however, R4 is -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R5 is hydrogen when it is -CN; however, A is hydrogen, halo, or -OR when B is hydrogen or halo. 52 Rather; however, A is hydrogen, halo, or -OR 52 When B is not hydrogen or halo; however, if B is halo, -NR 53 R 54 , -OR 55 , -SR 56 or -SO2R 57 When R7 is hydrogen, R6 is -OR only when XY is -CH2CH2-, -CH=CH-, -C≡C- or cyclopropyl. 63 And; however, R6 is -OR 63 When A is -OR 52 [Not; and however, when R6 is -F, A is not -Cl, -Br, or -I.] It is a compound of or a pharmaceutically acceptable salt, hydrate, or solvate of the compound.

[0068] In one embodiment, in the compound of formula (I), each R1 is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, halo, -C(O)NR8R9, -C(O)OR 10 , -NR 11 C(O)OR 12 , -NR 13 C(O)OR 14 -OC(O)OR 15 -CN, -CF3, -NR 16 SO2R 17 OR 18 m is 0, 1, 2 or 3; each R2 is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, halo, -C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29n is 0, 1 or 2; each R3 is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, halo, -C(O)NR 30 R 31 , -C(O)OR 32 , -NR 33 C(O)OR 34 , -NR 35 C(O)OR 36 -OC(O)OR 37 -CN, -CF3, -NR 38 SO2R 39 OR 40 And; q is 0, 1, 2 or 3; when q is 0, o is 0, 1 or 2; when q is 1, o is 0, 1, 2 or 3; when q is 2, o is 0, 1, 2, 3 or 4; when q is 3, o is 0, 1, 2, 3, 4 or 5; R4 is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, halo, -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R4 and R5 are either -CN, -CF3, or R4 and R5, together with the atom to which they are bonded, form a C4-C8 cycloalkyl ring; R5 is hydrogen, -F, -CF3, or alkyl; E is -CH2-, -CH2Z-, and Z is -NR 46 -, -S-, -SO2-, or -O-; E is -CH2-, -CH2Z, and Z is -NR 45-, -S-, -SO2- or -O-; when E is -CH2-, D is -(CH2)2-, -(CH2)3-, -CH=CHCH2-, -C(O)-, -C≡CCH2-, phenyl, cyclohexyl or cyclopentyl; Z is NR 45 When D is -O-, then D is -(CH2)2-, -(CH2)3-, -C(O)-, phenyl, cyclohexyl, or cyclopentyl; when Z is -SO2- or -S-, then D is -(CH2)2-, -(CH2)3-, phenyl, cyclohexyl, or cyclopentyl; XY is -C(O)NR 46 -, -NR 47 C(O)-, -C(O)O-, -CH2CH2-, -CH=CH-, -C≡C-, -NR 48 CH2-, -CH2NR 49 -, -O-CH2-, -CH2-O-, -SO2NR 50 -, -NR 51 SO2- or cyclopropyl; A is hydrogen, -OR 52 ,alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, or halo; B is hydrogen, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, halo, -NR 53 R 54 , -OR 55 , -SR 56 or -SO2-R 57 And; R8~R 53 and R 58 ~R 64These are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, -C(O)R 58 , -C(O)OR 59 -C(O)NR 60 R 61 or -SO2R 62 And; R 55 ~R 57 R5 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, or heteroarylalkynyl; R5 is hydrogen or fluoro; R6 is hydrogen, fluoro or -OR 63 And R7 is hydrogen, fluoro or -OR 64 That is the case.

[0069] In yet another embodiment, in the compound of formula (I), each R1 is independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR8R9, -C(O)OR 10 , -NR 11 C(O)OR 12 , -NR 13 C(O)OR 14 -OC(O)OR15 -CN, -CF3, -NR 16 SO2R 17 OR 18 m is either 0 or 1; each R2 is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 n is 0, 1 or 2; each R3 is independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR 30 R 31 , -C(O)OR 32 , -NR 33 C(O)OR 34 , -NR 35 C(O)OR 36 -OC(O)OR 37 -CN, -CF3, -NR 38 SO2R 39 OR 40And; q is 0, 1, 2 or 3; when q is 0, o is 0, 1 or 2; when q is 1, o is 0, 1, 2 or 3; when q is 2, o is 0, 1, 2, 3 or 4; when q is 3, o is 0, 1, 2, 3, 4 or 5; R4 is hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R4 and R5 are either -CN, -CF3, or R4 and R5, together with the atom to which they are bonded, form a C4-C8 cycloalkyl ring; R5 is hydrogen, -F, -CF3, or alkyl; E is -CH2-, -CH2Z-, and Z is -NR 46 -, -S-, -SO2-, or -O-; E is -CH2-, -CH2Z, and Z is -NR 45 -, -S-, -SO2- or -O-; when E is -CH2-, D is -(CH2)2-, -(CH2)3-, -CH=CHCH2-, -C(O)-, -C≡CCH2-, phenyl, cyclohexyl or cyclopentyl; Z is NR 45 When D is -O-, then D is -(CH2)2-, -(CH2)3-, -C(O)-, phenyl, cyclohexyl, or cyclopentyl; when Z is -SO2- or -S-, then D is -(CH2)2-, -(CH2)3-, phenyl, cyclohexyl, or cyclopentyl; XY is -C(O)NR 46 -, -NR 47 C(O)-, -C(O)O-, -CH2CH2-, -CH=CH-, -C≡C-, -NR 48 CH2-, -CH2NR 49 -, -O-CH2-, -CH2-O-, -SO2NR 50 -, -NR 51 SO2- or cyclopropyl; A is hydrogen, -OR 52,alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or halo; B is hydrogen, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -NR 53 R 54 , -OR 55 , -SR 56 or -SO2-R 57 And; R8~R 53 and R 58 ~R 64 These are independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, -C(O)R 58 , -C(O)OR 59 -C(O)NR 60 R 61 or -SO2R 62 And; R 55 ~R 57 R5 is alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl or heteroarylalkenyl; R5 is hydrogen or fluoro; R6 is hydrogen, fluoro or -OR 63And R7 is hydrogen, fluoro or -OR 64 That is the case.

[0070] In yet another embodiment, in the compound of formula (I), each R1 is independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR8R9, -C(O)OR 10 , -NR 11 C(O)OR 12 , -NR 13 C(O)OR 14 -OC(O)OR 15 -CN, -CF3, -NR 16 SO2R 17 OR 18 m is either 0 or 1; each R2 is independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 n is 0, 1 or 2; each R3 is independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR 30 R 31 , -C(O)OR32 , -NR 33 C(O)OR 34 , -NR 35 C(O)OR 36 -OC(O)OR 37 -CN, -CF3, -NR 38 SO2R 39 OR 40 And; q is 0, 1, 2 or 3; when q is 0, o is 0, 1 or 2; when q is 1, o is 0, 1, 2 or 3; when q is 2, o is 0, 1, 2, 3 or 4; when q is 3, o is 0, 1, 2, 3, 4 or 5; R4 is hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R4 and R5 are either -CN, -CF3, or R4 and R5, together with the atom to which they are bonded, form a C4-C8 cycloalkyl ring; R5 is hydrogen, -F, -CF3, or alkyl; E is -CH2-, -CH2Z-, and Z is -NR 46 -, -S-, -SO2-, or -O-; E is -CH2-, -CH2Z, and Z is -NR 45 -, -S-, -SO2- or -O-; when E is -CH2-, D is -(CH2)2-, -(CH2)3-, -CH=CHCH2-, -C(O)-, -C≡CCH2-, phenyl, cyclohexyl or cyclopentyl; Z is NR 45 When D is -O-, then D is -(CH2)2-, -(CH2)3-, -C(O)-, phenyl, cyclohexyl, or cyclopentyl; when Z is -SO2- or -S-, then D is -(CH2)2-, -(CH2)3-, phenyl, cyclohexyl, or cyclopentyl; XY is -C(O)NR 46 -, -NR 47C(O)-, -C(O)O-, -CH2CH2-, -CH=CH-, -C≡C-, -NR 48 CH2-, -CH2NR 49 -, -O-CH2-, -CH2-O-, -SO2NR 50 -, -NR 51 SO2- or cyclopropyl; A is hydrogen, -OR 52 ,alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or halo; B is hydrogen, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, halo, -NR 53 R 54 , -OR 55 , -SR 56 or -SO2-R 57 And; R8~R 53 and R 58 ~R 64 These are independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, -C(O)R 58 , -C(O)OR 59 -C(O)NR 60 R 61 or -SO2R 62 And; R 55 ~R 57R5 is alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl or heteroarylalkenyl; R5 is hydrogen or fluoro; R6 is hydrogen, fluoro or -OR 63 And R7 is hydrogen, fluoro or -OR 64 That is the case.

[0071] In yet another embodiment, in the compound of formula (I), each R1 is independently hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroalkyl, heteroaryl, halo, -C(O)NR8R9, -C(O)OR 10 , -NR 11 C(O)OR 12 , -NR 13 C(O)OR 14 -OC(O)OR 15 -CN, -CF3, -NR 16 SO2R 17 OR 18 m is either 0 or 1; each R2 is independently hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroalkyl, heteroaryl, heteroarylalkyl, halo, -C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 n is 0, 1 or 2; each R3 is independently hydrogen, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroalkyl, heteroalkynyl, heteroaryl, heteroarylalkyl, halo, -C(O)NR 30 R 31 , -C(O)OR32 , -NR 33 C(O)OR 34 , -NR 35 C(O)OR 36 -OC(O)OR 37 -CN, -CF3, -NR 38 SO2R 39 OR 40 And; q is 0, 1, 2 or 3; when q is 0, o is 0, 1 or 2; when q is 1, o is 0, 1, 2 or 3; when q is 2, o is 0, 1, 2, 3 or 4; when q is 3, o is 0, 1, 2, 3, 4 or 5; R4 is hydrogen, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, cycloheteroalkenyl, heteroalkyl, heteroaryl, heteroarylalkyl, halo, -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 R4 and R5 are either -CN, -CF3, or R4 and R5, together with the atom to which they are bonded, form a C4-C8 cycloalkyl ring; R5 is hydrogen, -F, -CF3, or alkyl; E is -CH2-, -CH2Z-, and Z is -NR 46 -, -S-, -SO2-, or -O-; E is -CH2-, -CH2Z, and Z is -NR 45 -, -S-, -SO2- or -O-; when E is -CH2-, D is -(CH2)2-, -(CH2)3-, -CH=CHCH2-, -C(O)-, -C≡CCH2-, phenyl, cyclohexyl or cyclopentyl; Z is NR 45 When D is -O-, then D is -(CH2)2-, -(CH2)3-, -C(O)-, phenyl, cyclohexyl, or cyclopentyl; when Z is -SO2- or -S-, then D is -(CH2)2-, -(CH2)3-, phenyl, cyclohexyl, or cyclopentyl; XY is -C(O)NR 46 -, -NR 47 C(O)-, -C(O)O-, -CH2CH2-, -CH=CH-, -C≡C-, -NR 48CH2-, -CH2NR 49 -, -O-CH2-, -CH2-O-, -SO2NR 50 -, -NR 51 SO2- or cyclopropyl; A is hydrogen, -OR 52 ,alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, heteroalkyl, heteroalkenyl, heteroaryl, heteroarylalkyl or halo; B is hydrogen, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroalkyl, heteroaryl, heteroarylalkyl, halo, -NR 53 R 54 , -OR 55 , -SR 56 or -SO2-R 57 And; R8~R 53 and R 58 ~R 64 These are independently hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroalkyl, heteroaryl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroalkyl, heteroaryl, heteroarylalkyl, -C(O)R 58 , -C(O)OR 59 -C(O)NR 60 R 61 or -SO2R 62 And; R 55 ~R 57 R5 is alkyl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroalkyl, heteroaryl, or heteroarylalkyl; R5 is hydrogen or fluoro; R6 is hydrogen, fluoro, or -OR 63 And R7 is hydrogen, fluoro or -OR 64 That is the case.

[0072] In one embodiment, equation (II) [ka] The compound is provided.

[0073] Other embodiments, formula (III) [ka] The compound is provided.

[0074] In another embodiment, formula (IV) [ka] The compound is provided.

[0075] In yet another embodiment, formula (V) [ka] The compound is provided.

[0076] In another embodiment, formula (VI) [ka] The compound is provided.

[0077] In some embodiments of the compounds of formula (I-VI), each R1 is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, phenyl, substituted phenyl, cycloalkyl, heteroalkyl, cycloheteroalkyl, -F, -C(O)NR8R9, -C(O)OR 10 -OC(O)OR 15 -CF3 or -OR 18 In other embodiments, each R1 is independently a (C1-C4) alkyl, a (C2-C4) alkenyl, a phenyl, a substituted phenyl, a (C5-C7) cycloalkyl, a (C5-C7) cycloheteroalkyl, -F, or -CF3.

[0078] In some embodiments of the compounds of formulas (I-VI), m is 0 or 1. In other embodiments, n is 0 or 1.

[0079] In some embodiments of the compounds of formula (I-VI), each R2 is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heteroalkyl, cycloheteroalkyl or cycloheteroalkenyl, halo, -C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 In other embodiments, each R2 can independently be (C1-C4) alkyl, (C2-C4) alkenyl, phenyl, substituted phenyl, (C5-C7) cycloalkyl, (C5-C7) cycloheteroalkyl, halo, or C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 That is the case.

[0080] In some embodiments of the compounds of formula (I-VI), each R3 is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, phenyl, substituted phenyl, cycloalkyl, heteroalkyl, cycloheteroalkyl, -F, -C(O)NR 30 R 31 , -C(O)OR 32 -OC(O)OR 37 -CF3 or -OR 40 That is 。In other embodiments, each R3 is independently a (C1-C4) alkyl, a (C2-C4) alkenyl, a phenyl, a substituted phenyl, a (C5-C7) cycloalkyl, a (C5-C7) cycloheteroalkyl, -F, or -CF3.

[0081] In one embodiment of the compounds of formula (I-VI), o is 0 or 1. In another embodiment, o is 0, 1, 2, or 3. In one embodiment, o is 1, 2, or 3. In one embodiment, o is 1 or 2.

[0082] In some embodiments of the compounds of formula (I-VI), R4 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, -F, -C(O)NR 41 R 42 , -C(O)R 43 , -C(O)OR 44 or -CF3. In other embodiments of the compounds of formula (I-VI), R4 is hydrogen, (C1-C4) alkyl, (C2-C4) alkenyl, -F, or -CF3.

[0083] In some embodiments of formulas (I-VI), R5 is hydrogen or -F.

[0084] In some embodiments of the compounds of formula (I-VI), R8-R 53 and R 58 ~R 64 R8~R 53 and R 58 ~R 64 These are independently hydrogen, (C1-C4) alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, cycloheteroalkyl, or substituted cycloheteroalkyl.

[0085] In some embodiments of compounds of formula (I-VI), R 55 ~R 57 R is independently alkyl, alkenyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl, heteroalkenyl, heteroaryl, substituted heteroaryl, cycloheteroalkyl, or substituted cycloheteroalkyl. In other embodiments, R 55 ~R 57 These are independently (C1-C4) alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, cycloheteroalkyl, or substituted cycloheteroalkyl.

[0086] In some embodiments of the compounds of formula (I-VI), each R1 is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, phenyl, substituted phenyl, cycloalkyl, heteroalkyl, cycloheteroalkyl, -F, -C(O)NR8R9, -C(O)OR 10 -OC(O)OR 15 -CF3 or -OR 18 There is m, and m is either 0 or 1, and each R2 is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heteroalkyl, cycloheteroalkyl, halo, -C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 There is a difference between n and 1, and each R3 is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, phenyl, substituted phenyl, cycloalkyl, heteroalkyl, cycloheteroalkyl, -F-C(O)NR 30 R 31, -C(O)OR 32 -OC(O)OR 37 -CF3 or -OR 40 Here, o is 0, 1, 2 or 3, and R4 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, -F, -C(O)NR 41 R 42 , -C(O)OR 43 , -C(O)OR 44 Or -CF3, R8~R 53 and R 58 ~R 64 R1 is independently hydrogen, alkyl, alkenyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl, heteroalkenyl, heteroaryl, substituted heteroaryl, cycloheteroalkyl, or substituted cycloheteroalkyl. In other embodiments, R1 is independently (C1-C4)alkyl, (C2-C4)alkenyl, phenyl, substituted phenyl, (C5-C7)cycloalkyl, (C5-C7)cycloheteroalkyl, -F, or -CF3, m is 0 or 1, and each R2 is independently (C1-C4)alkyl, (C2-C4)alkenyl, phenyl, substituted phenyl, (C5-C7)cycloalkyl, (C5-C7)cycloheteroalkyl, halo, C(O)NR 19 R 20 , -C(O)OR 21 , -NR 22 C(O)OR 23 , -NR 24 C(O)OR 25 -OC(O)OR 26 -CN, -CF3, -NR 27 SO2R 28 OR 29 R8~R 53 and R 58 ~R 64These are independently hydrogen, (C1-C4) alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, cycloheteroalkyl, or substituted cycloheteroalkyl.

[0087] In some embodiments of the compounds of formula (I, II, IV, and V), A is an aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, or substituted cycloheteroalkenyl. In other embodiments, A is an aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl. In yet another embodiment of the compounds of formula (I, II, IV, and V), A is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl.

[0088] In some embodiments of the compounds of formula (I, III, IV, and VI), B is aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkenyl, substituted heteroarylalkenyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloheteroalkenyl, or substituted cycloheteroalkenyl. In other embodiments, B is aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl. In yet another embodiment, B is aryl, substituted aryl, heteroaryl, or substituted heteroaryl. In yet another embodiment, B is -NR 53 R 54 In another embodiment, B is -NHR 54 , R 54 is aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl-C(O)R 58 , -C(O)OR 59 or -SO2R 62 In another embodiment, B is -NHR 54 and R 54 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, -C(O)R 58 , -C(O)OR 59 or -SO2R 62 That is so.

[0089] In some embodiments of the compounds of formulas (I) and (IV), A is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl, and B is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl. In other embodiments of formulas (I) and (IV), A is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl, and B is -NR53 R 54 Furthermore, in other embodiments of formulas (I) and (IV), A is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl, and B is -NHR 54 And R 54 is aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl-C(O)R 58 , -C(O)OR 59 or -SO2R 62 Furthermore, in other embodiments of formulas (I) and (IV), A is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl, and B is -NHR 54 And R 54 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, -C(O)R 58 , -C(O)OR 59 or -SO2R 62 That is the case.

[0090] In one embodiment, equation (VII) [ka] The compound is provided.

[0091] In one embodiment, A is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl. In another embodiment, A is an aryl, substituted phenyl, heteroaryl, or substituted heteroaryl.

[0092] In one embodiment, equation (VIIII) [ka] The compound is provided.

[0093] In one embodiment, B is an aryl, substituted aryl, heteroaryl, or substituted heteroaryl. In another embodiment, B is an aryl, substituted phenyl, heteroaryl, or substituted heteroaryl. In yet another embodiment, B is -NHR 54 And R 54 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, -C(O)R 58 , -C(O)OR 59 or -SO2R 62 That is the case.

[0094] In one embodiment, formula (IX) [ka] The compound is provided.

[0095] In one embodiment, A is phenyl or a substituted phenyl.

[0096] In one embodiment, equation (Ia) [ka] In the compound or a pharmaceutically acceptable salt thereof, q is 1, 2, or 3; R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -C(O)OR 11 Selected from ,=O,=S and -CN; m is selected from 0, 1, 2, 3, 4, 5, and 6; o is selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl, -OR12 , -SR 12 , -N(R 12 ) Selected from -CN and -NO2; n is 0, 1, or 2; R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 ) Selected from 2 and -CN; or R 4 and R 5 These are combined as =O, =S and =N(R 13 ) forms a double bond substituent selected from; D is selected from the bonds, -C(O)-, -C≡CCH2-, and -CH=CHCH2-; E is C 1-4 Selected from alkylenes and -(CH2)Z-, Here, Z is selected from -NH-, -S-, -SO2-, and -O-; XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(O)O-, λ -C(R 15 )2C(R 15 )2-, λ -CH=CH-, λ -C≡C-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2-, λ -C(R 15 )2O-, λ -SO2N(R 14 )-and λ -N(R14 ) Selected from SO2-; Here, λ From XY [ka] It means a connection to; R 6 and R 7 Each of these is independently hydrogen, halogen, and C in each case. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 Selected from and -CN; A is (i) and (ii): (i) Hydrogen, halogens and -CN or A and R 6 They become one C 3-6 Forms a carbon ring or a 3- to 6-membered heteroring; (ii)-OR 17 , -SR 17 , -N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -S(O)R 17 -S(O)2R 17 and -S(O)2N(R 17 )2; C 1-6 Alkyl (depending on the case: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), -N3 and -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17), substituted with one or more substituents independently selected from -N3 and -CN); and C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), -N3 and -CN; Depending on the situation, halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from; When A is selected from (ii), B is selected from (I), or when A is selected from (i), B is selected from (II): (I) Hydrogen, halogens and -CN or B and R 7 They become one C 3-6 Forms a carbon ring or a 3- to 6-membered heteroring; (II)-OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 and -S(O)2N(R 18 )2; C 1-6 Alkyl (depending on the case: Halogen, -OR18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3, -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 Carbon rings and 3-10 membered heterorings may contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), substituted with one or more substituents independently selected from -N3 and -CN); and C 3-12 Carbon rings and 3- to 12-membered heterorings [both depending on the case: C 3-6 Carbon rings and 3-6 membered heterorings (both can contain halogens, C) 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )C(O)OR 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(S)N(R 21 )2, -N(R 21 )S(O)2(R 21 ), -S(O)R 21 -S(O)2R 21 -S(O)2N(R 21 )2, -NO2, =O, =S, =N(R 21 (Substituted with one or more substituents independently selected from -N3 and -CN) [Substituted with one or more substituents independently selected from;] R 11 , R 12 , R 13 , R 14 and R 16 Each of them is independently hydrogen, C in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R 15Independently, hydrogen, halogen, and C are used in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R 17 Each case is independent: hydrogen; Depending on the situation, halogen, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 -NO2, =O, =S, =N(R 21 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )C(O)OR 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(S)N(R 21 )2, -N(R 21 )S(O)2(R 21 ), -S(O)R 21 -S(O)2R 21 -S(O)2N(R 21 )2, -NO2, =O, =S, =N(R 21 ), C substituted with one or more substituents independently selected from -N3 and -CN 3-6Carbon rings and 3- to 6-membered heterorings Selected from; R 18 Each case is independent: hydrogen; C 1-6 Alkyl (depending on the case: Halogen, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 and -N(R 22 ) Substituted with one or more substituents independently selected from 2); and C 3-10 Carbon rings and 3- to 10-membered heterorings (both depending on the case): Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 , -N(R 22 )C(O)N(R22 )2, -N(R 22 )C(S)N(R 22 )2, -N(R 22 )S(O)2(R 22 ), -S(O)R 22 -S(O)2R 22 -S(O)2N(R 22 )2, -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 (Substituted with one or more substituents independently selected from the haloalkyl group.) Selected from; R 21 and R 22 Each is independent in its own case: hydrogen; C 1-4 Alkyl (sometimes halogen, hydroxyl, C) 3-6 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocyclic rings, where each C 3-6 Carbon rings and 3-6 membered heterorings are sometimes C 1-4 Alkyl, -N(R 23 )2 and -C(O)N(R 23 ) Substituted with one or more substituents independently selected from 2); and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 C substituted with one or more substituents independently selected from alkoxy and =O 3-6 Carbon rings and 3- to 12-membered heterorings Selected from; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0097] In one embodiment, equation (IIa) [ka] A compound or a pharmaceutically acceptable salt thereof is provided, where, q is 1, 2, or 3; R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -C(O)OR 11 Selected from ,=O,=S and -CN; m is selected from 0, 1, 2, 3, 4, 5, and 6; o is selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 ) Selected from -CN and -NO2; n is 0, 1, or 2; R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 ) Selected from 2 and -CN; or R 4 and R 5 These are combined as =O, =S and =N(R 13 ) forms a double bond substituent selected from; D is selected from the bonds, -C(O)-, -C≡CCH2-, and -CH=CHCH2-; E is C 1-4 Selected from alkylenes and -(CH2)Z-, Here, Z is selected from -NH-, -S-, -SO2-, and -O-; XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(O)O-, λ -C(R 15 )2C(R 15 )2-, λ -CH=CH-, λ -C≡C-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2-, λ -C(R 15 )2O-, λ -SO2N(R 14 )-and λ -N(R 14 ) Selected from SO2-; Here, λ From XY [ka] It means a connection to; R 6 and R 7 Each of these is independently hydrogen, halogen, and C in each case. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 Selected from and -CN; A is -OR 17 , -SR 17 , -N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17)2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -S(O)R 17 -S(O)2R 17 and -S(O)2N(R 17 )2; C 1-6 Alkyl (depending on the case: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), -N3 and -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 17 , -SR 17 , -N(R17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2, -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), substituted with one or more substituents independently selected from -N3 and -CN); and C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17), -N3 and -CN; Depending on the situation, halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from; R 11 , R 12 , R 13 , R 14 and R 16 Each of them is independently hydrogen, C in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R 15 Independently, hydrogen, halogen, and C are used in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R17 Each case is independent: hydrogen; Depending on the situation, halogen, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 -NO2, =O, =S, =N(R 21 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )C(O)OR 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(S)N(R 21 )2, -N(R 21 )S(O)2(R 21 ), -S(O)R 21 -S(O)2R 21 -S(O)2N(R 21 )2, -NO2, =O, =S, =N(R 21 ), C substituted with one or more substituents independently selected from -N3 and -CN 3-6 Carbon rings and 3- to 6-membered heterorings Selected from; R 21 Each case is independent: hydrogen; Depending on the case, halogens, hydroxyls, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-4 Alkyl (where each C 3-6 Carbon rings and 3-6 membered heterorings are sometimes C 1-4 Alkyl, -N(R 23 )2 and -C(O)N(R 23 ) Substituted with one or more substituents independently selected from 2); and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 C substituted with one or more substituents independently selected from alkoxy and =O 3-6 Carbon rings and 3- to 12-membered heterorings Selected from; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0098] In other embodiments, formula (IIIa) [ka] A compound or a pharmaceutically acceptable salt thereof is provided, here: q is 1, 2, or 3; R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -C(O)OR 11 Selected from ,=O,=S and -CN; m is selected from 0, 1, 2, 3, 4, 5, and 6; o is selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8; R 2 Independently, halogen, C in each case1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 ) Selected from -CN and -NO2; n is 0, 1, or 2; R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 ) Selected from 2 and -CN; or R 4 and R 5 These are combined as =O, =S and =N(R 13 ) forms a double bond substituent selected from; D is selected from the bonds, -C(O)-, -C≡CCH2-, and -CH=CHCH2-; E is C 1-4 Selected from alkylenes and -(CH2)Z-, Here, Z is selected from -NH-, -S-, -SO2-, and -O-; XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(O)O-, λ -C(R 15 )2C(R 15 )2-, λ -CH=CH-, λ -C≡C-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2-, λ -C(R 15 )2O-, λ-SO2N(R 14 )-and λ -N(R 14 ) Selected from SO2-; Here, λ From XY [ka] It means a connection to; R 6 and R 7 Each of these is independently hydrogen, halogen, and C in each case. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 Selected from and -CN; B is: -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 and -S(O)2N(R 18 )2; C 1-6 Alkyl (depending on the case: Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3, -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 Carbon rings and 3-10 membered heterorings may contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), substituted with one or more substituents independently selected from -N3 and -CN); and C 3-12Carbon rings and 3- to 12-membered heterorings (both depending on the case): In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -SR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )C(O)OR 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(S)N(R 21 )2, -N(R 21 )S(O)2(R 21 ), -S(O)R 21 -S(O)2R 21 -S(O)2N(R 21 )2, -NO2, =O, =S, =N(R 21 ), C substituted with one or more substituents independently selected from -N3 and -CN 3-6 Carbon rings and 3- to 6-membered heterorings (Substituted with one or more substituents independently selected from) Selected from; R 11 , R 12 , R 13 , R 14 and R 16 Each of them is independently hydrogen, C in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R 15 Independently, hydrogen, halogen, and C are used in each case. 1-4 Alkyl and C 1-4 Selected from haloalkyl groups; R 18 Each case is independent: hydrogen; C 1-6Alkyl (depending on the case: Halogen, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 and -N(R 22 ) Substituted with one or more substituents independently selected from 2); and C 3-10 Carbon rings and 3- to 10-membered heterorings (both depending on the case): Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 , -N(R 22 )C(O)N(R 22 )2, -N(R 22 )C(S)N(R 22 )2, -N(R 22 )S(O)2(R 22 ), -S(O)R22 -S(O)2R 22 -S(O)2N(R 22 )2, -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 (Substituted with one or more substituents independently selected from the haloalkyl group.) Selected from; R 22 Each case is independent: hydrogen; C 1-4 Alkyl (sometimes halogen, hydroxyl, C) 3-6 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocyclic rings, where each C 3-6 Carbon rings and 3-6 membered heterorings are sometimes C 1-4 Alkyl, -N(R 23 )2 and -C(O)N(R 23 ) Substituted with one or more substituents independently selected from 2); and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 C substituted with one or more substituents independently selected from alkoxy and =O 3-6 Carbon rings and 3- to 12-membered heterorings Selected from; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0099] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), q is 1, 2, or 3. In one embodiment, q is selected from 1, 2, and 3. In one embodiment, q is selected from 1 and 2. In one embodiment, q is selected from 2 and 3. In one embodiment, q is 1. In one embodiment, q is 2. In one embodiment, q is 3.

[0100] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -C(O)OR 11 Selected from , =O and -CN. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -C(O)OR 11 And is selected from = O. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -C(O)OR 11 and -CN are selected. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11)2 and -C(O)OR 11 Selected from. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 ,-C(O)N(R 11 )2 and -C(O)OR 11 Selected from. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -C(O)N(R) 11 )2 and -C(O)OR 11 Selected from. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl and -C(O)N(R) 11 ) Selected from 2. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl, -C(O)N(R 11 )2 and -C(O)OR 11 Selected from. In one embodiment, R 1 and R 3 Each of them is independently halogen, C 1-4 Alkyl and -C(O)N(R) 11 ) Selected from 2.

[0101] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), m is selected from 0, 1, 2, 3, 4, 5, and 6. In one embodiment, m is selected from 0, 1, 2, 3, 4, and 5. In one embodiment, m is selected from 0, 1, 2, 3, and 4. In one embodiment, m is selected from 1, 2, 3, and 4. In one embodiment, m is selected from 0, 1, 2, and 3. In one embodiment, m is selected from 0, 1, and 2. In one embodiment, m is selected from 0 and 1. In one embodiment, m is 0. In one embodiment, m is 1. In one embodiment, m is 2. In one embodiment, m is 3. In one embodiment, m is 4. In one embodiment, m is 5. In one embodiment, m is 6.

[0102] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), o is selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8. In one embodiment, o is selected from 0, 1, 2, 3, 4, 5, 6, and 7. In one embodiment, o is selected from 0, 1, 2, 3, 4, 5, and 6. In one embodiment, o is selected from 0, 1, 2, 3, 4, and 5. In one embodiment, o is selected from 0, 1, 2, 3, and 4. In one embodiment, o is selected from 1, 2, 3, and 4. In one embodiment, o is selected from 0, 1, 2, and 3. In one embodiment, o is selected from 0, 1, and 2. In one embodiment, o is selected from 0 and 1. In one embodiment, o is 0. In one embodiment, o is 1. In one embodiment, o is 2. In one embodiment, o is 3. In one embodiment, o is 4. In one embodiment, o is 5. In one embodiment, o is 6. In one embodiment, o is 7. In one embodiment, o is 8.

[0103] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 2Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 ) Selected from 2 and -CN. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -N(R 12 ) Selected from 2 and -CN. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 and -CN are selected. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl, -N(R) 12 ) Selected from 2 and -CN. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 and -N(R 12 ) Selected from 2. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Selected from haloalkyl and -CN. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl and -N(R) 12 ) Selected from 2. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl, C 1-4 Haloalkyl and -OR 12 Selected from. In one embodiment, R 2 Independently, halogen, C in each case 1-4 Alkyl and C 1-4 Selected from haloalkyls. In one embodiment, R2 R is independently selected from halogens in each case. In one embodiment, R 2 Each case C is independent 1-4 Selected from alkyl groups. In one embodiment, R 2 Each case C is independent 1-4 Selected from haloalkyl groups.

[0104] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), n is 0, 1, or 2. In one embodiment, n is selected from 0, 1, and 2. In one embodiment, n is selected from 0 and 1. In one embodiment, n is selected from 1 and 2. In one embodiment, n is 0. In one embodiment, n is 1. In one embodiment, n is 2.

[0105] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 ) Selected from 2 and -CN; or R 4 and R 5 These are combined as =O, =S and =N(R 13 ) forms a double bond substituent selected from. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -N(R 13 ) Selected from 2 and -CN; or R 4 and R 5 These are combined into =O and =N(R 13 ) forms a double bond substituent selected from. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C.1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -N(R 13 ) Selected from 2 and -CN; or R 4 and R 5 They come together to form =O. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , and-N(R 13 ) Selected from 2; or R 4 and R 5 These are combined into =O and =N(R 13 ) forms a double bond substituent selected from. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , and-N(R 13 ) Selected from 2; or R 4 and R 5 They come together to form =O. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl and -OR 13 Selected from; or R 4 and R 5 They come together to form =O. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl and -N(R) 13 ) Selected from 2; or R 4 and R 5 They come together to form =O. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl and C 1-4Selected from haloalkyl groups; or R 4 and R 5 They come together to form =O. In one embodiment, R 4 and R 5 These are hydrogen, halogen, and C, respectively, independently. 1-4 Selected from alkyl; or R 4 and R 5 They come together to form =O.

[0106] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -SR 13 , -N(R 13 ) Selected from 2 and -CN. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 , -N(R 13 ) Selected from 2 and -CN. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 and -N(R 13 ) Selected from 2. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 13 and -CN are selected. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Haloalkyl, -N(R) 13 ) Selected from 2 and -CN. In one embodiment, R 4and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl, C 1-4 Selected from haloalkyl and -CN. In one embodiment, R 4 and R 5 Each of them independently consists of hydrogen, halogen, and C. 1-4 Alkyl and C 1-4 Selected from haloalkyls. In one embodiment, R 4 and R 5 These are hydrogen, halogen, and C, respectively, independently. 1-4 Selected from alkyl groups. In one embodiment, R 4 and R 5 Each is independently selected from hydrogen and halogen. In one embodiment, R 4 and R 5 Each of them is hydrogen.

[0107] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 4 and R 5 These are combined as =O, =S and =N(R 13 ) forms a double bond substituent selected from. In one embodiment, R 4 and R 5 These are combined into =O and =N(R 13 ) forms a double bond substituent selected from. In one embodiment, for a compound or salt of formula (I), R 4 and R 5 These together form a double bond substituent selected from =O and =S. In one embodiment, R 4 and R 5 They come together to form =O.

[0108] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), D is selected from a bond, -C(O)-, and -C≡CCH2-. In one embodiment, D is selected from a bond, -C(O)-, and -CH=CHCH2-. In one embodiment, D is selected from a bond and -C(O)-. In one embodiment, D is a bond. In one embodiment, D is -C(O)-.

[0109] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), E is C 1-4 Selected from alkylenes. In one embodiment, E is selected from -(CH2)Z-, where Z is selected from -NH-, -S-, -SO2- and -O-. In one embodiment, E is C 1-4 Selected from alkylene and -(CH2)Z-, where Z is selected from -NH-, -S-, and -O-. In one embodiment, E is C 1-4 Selected from alkylene and -(CH2)Z-, where Z is selected from -NH-, -SO2-, and -O-. In one embodiment, E is C 1-4 Selected from alkylene and -(CH2)Z-, where Z is selected from -NH- and -O-.

[0110] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), D is selected from a bond and -C(O)-; and E is C 1-4 Selected from alkylenes. In one embodiment, D is a bond; and E is C 1-4 Selected from alkylenes. In one embodiment, D is -C(O)- and E is C 1-4 Selected from alkylenes.

[0111] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), XY is: λ -C(O)N(R 14 )-, λ -N(R14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(O)O-, λ -C(R 15 )2C(R 15 )2-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2-, λ -C(R 15 )2O-, λ -SO2N(R 14 )-and λ -N(R 14 ) Selected from SO2-; here, λ From XY [ka] It means a union to. For one reason, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(O)O-, λ -C(R 15 )2C(R 15 )2-, λ -CH=CH-, λ -C≡C-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ-C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(R 15 )2C(R 15 )2-, λ -CH=CH-, λ -C≡C-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2-, λ -C(R 15 )2O-, λ -SO2N(R 14 )-and λ -N(R 14 ) Selected from SO2-. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(O)O-, λ -C(R 15 )2C(R 15 )2-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R14 )C(O)C(R 15 )2-, λ -C(R 15 )2C(R 15 )2-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2-, λ -C(R 15 )2O-, λ -SO2N(R 14 )-and λ -N(R 14 ) Selected from SO2-. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)C(R 15 )2-, λ -C(R 15 )2C(R 15 )2-, λ -CH=CH-, λ -C≡C-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2- and λ -C(R 15 ) Selected from 2O-.

[0112] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -C(R 15 )2C(R 15)2-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -O-, λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R14 )C(O)-, λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ -C(O)N(R 14 )-and λ -N(R 14 )C(O)- is selected. In one embodiment, XY is λ -OC(R 15 )2- and λ -C(R 15 )2O- is selected. In one embodiment, XY is λ -C(O)N(R 14 )- and in one embodiment, XY is λ -N(R 14 )C(O)-. In one embodiment, XY is λ -C(R 15 )2C(R 15 )2-. In one embodiment, XY is λ -N(R 14 )C(R 15 )2-. In one embodiment, XY is λ -C(R 15 )2N(R 14 )-. In one embodiment, XY is λ -O-. In one embodiment, XY is λ -OC(R 15 )2-. In one embodiment, XY is λ -C(R 15 It is 2O-.

[0113] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(O)CH2-, λ -CH2CH2-, λ -N(R14 )CH2-, λ -CH2N(R 14 )-, λ -O-, λ -OCH2- and λ Selected from -CH2O-; and R 14 In each case, hydrogen and C 1-4 Alkyl. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -N(R 14 )C(R 15 )2-, λ -C(R 15 )2N(R 14 )-, λ -OC(R 15 )2- and λ -C(R 15 ) Selected from 2O- and selected from; R 14 In each case, hydrogen and C 1-4 Selected from alkyl groups. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -OC(R 15 )2- and λ -C(R 15 ) Selected from 2O-; R 14 In each case, hydrogen and C 1-4 Selected from alkyl groups. In one embodiment, XY is λ -C(O)N(R 14 )-, λ -N(R 14 )C(O)-, λ -OC(R 15 )2- and λ -C(R 15 ) Selected from 2O-; R 14 In each case, hydrogen and C 1-4 Selected from alkyl groups. In one embodiment, XY is λ -C(O)N(R 14 )-and λ -N(R 14)C(O)- selected;R 14 In each case, hydrogen and C 1-4 Selected from alkyl groups.

[0114] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), XY is λ -C(O)N(H)-, λ -N(H)C(O)-, λ -CH2CH2-, λ -N(H)CH2-, λ -CH2N(H)-, λ -O-, λ -OCH2- and λ Selected from -CH2O-. In one embodiment, XY is λ -C(O)N(H)-, λ -N(H)C(O)-, λ -N(H)CH2-, λ -CH2N(H)-, λ -O-, λ -OCH2- and λ Selected from -CH2O-. In one embodiment, XY is λ -C(O)N(H)-, λ -N(H)C(O)-, λ -N(H)CH2-, λ -CH2N(H)-, λ -OCH2- and λ Selected from -CH2O-. In one embodiment, XY is λ -C(O)N(H)-, λ -N(H)C(O)-, λ -OCH2- and λ Selected from -CH2O-. In one embodiment, XY is λ -C(O)N(H)-, λ -N(H)C(O)-, λ -OCH2- and λ Selected from -CH2O-. In one embodiment, XY is λ -C(O)N(H)- and λ Selected from -N(H)C(O)-. In one embodiment, XY is λ -OCH2- andλ Selected from -CH2O-. In one embodiment, XY is λ It is -C(O)N(H)-. In one embodiment, XY is λ It is -N(H)C(O)-. In one embodiment, XY is λ It is -CH2CH2-. In one embodiment, XY is λ It is -N(H)CH2-. In one embodiment, XY is λ It is -CH2N(H)-. In one embodiment, XY is λ -O-. In one embodiment, XY is λ -OCH2-. In one embodiment, XY is λ It is -CH2O-.

[0115] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 6 and R 7 Each of these is independently hydrogen, halogen, and C in each case. 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 ) Selected from 2 and -CN. In one embodiment, R 6 and R 7 Each of these is independently hydrogen, halogen, and C in each case. 1-4 Alkyl, C 1-4 Haloalkyl and -OR 16 Selected from. In one embodiment, R 6 and R 7 Each of these is independently hydrogen, halogen, and C in each case. 1-4 Alkyl and -OR 16 Selected from. In one embodiment, R 6 and R 7 Each of these is independently hydrogen, halogen, and -OR in each case. 16 Selected from. In one embodiment, R 6 and R 7 Each is independently selected from hydrogen and halogen in each case. In one embodiment, R 6 and R 7Each of them independently contains hydrogen and -OR 16 Selected from. In one embodiment, R 6 and R 7 Each of them is hydrogen.

[0116] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is (i) and (ii): (i) Hydrogen, halogens and -CN or A and R 6 They become one C 3-6 Forming a carbon ring or a 3-6 membered heteroring; and (ii)C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), -N3 and -CN; Depending on the situation, halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 )2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from.

[0117] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is (i) and (ii): (i) hydrogen; and (ii)C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from.

[0118] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is (i) and (ii): (i) hydrogen; and (ii)C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen, -OR17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2(R 17 ), -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2(R 17 ), -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from.

[0119] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is (i) and (ii): (i) hydrogen; and (ii)C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen, -OR 17 , -N(R 17)2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from.

[0120] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is (i) and (ii): (i) hydrogen; and (ii)C 3-12 Carbon rings and 3-12 membered heterorings (both potentially halogenated;-OR) 17 ;C which may be substituted with one or more substituents selected independently of halogens. 1-6 Alkyl; and in both cases halogen, C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocyclic rings; where R 17 Independently, hydrogen and C are in each case. 1-6Alkyl, C 3-6 (Selected from carbocyclic and 3- to 6-membered heterocycles) Selected from.

[0121] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is selected from hydrogen, halogen, and -CN, or A and R 6 They become one C 3-6 It forms a carbon ring or a 3-6 membered heteroring. In one embodiment, A is selected from hydrogen and halogen or A and R 6 They become one C 3-6 It forms a carbon ring. In one embodiment, A is hydrogen or A and R 6 They become one C 3-6 A carbon ring is formed. In one embodiment, A is selected from hydrogen, halogen and -CN. In one embodiment, A is selected from hydrogen and halogen. In one embodiment, A is selected from hydrogen and -CN. In one embodiment, A is hydrogen. In one embodiment, A and R 6 They become one C 3-6 They form a carbon ring or a 3-6 membered heteroring. In one embodiment, A and R 6 They become one C 3-6 It forms a carbon ring.

[0122] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12 Selected from carbocyclic and 3- to 12-membered heterocycles, in either case: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17)C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), -N3 and -CN; Depending on the situation, halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )C(S)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O, =S, =N(R 17 ), C substituted with one or more substituents independently selected from -N3 and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0123] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12 Selected from carbocyclic and 3- to 12-membered heterocycles, in either case: Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0124] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12 Selected from carbocyclic and 3- to 12-membered heterocycles, in either case: Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0125] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12Selected from carbon rings and 3- to 12-membered heterorings, both of which may be halogens;-OR 17 ;C which may be substituted with one or more substituents selected independently of halogens. 1-6 Alkyl; and in both cases halogen, C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles.

[0126] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 17 Each case is independent: hydrogen; Depending on the situation, halogen, -OR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 C is substituted with one or more substituents independently selected from -NO2, =O and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-OC(O)N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )C(O)OR 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(S)N(R21 )2, -N(R 21 )S(O)2(R 21 ), -S(O)R 21 -S(O)2R 21 -S(O)2N(R 21 )C substituted with one or more substituents independently selected from -NO2, -O and -CN 3-6 Carbon rings and 3- to 6-membered heterorings Selected from.

[0127] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 17 Each case is independent: hydrogen; Depending on the situation, halogen, -OR 21 , -N(R 21 )2, -C(O)OR 21 -OC(O)R 21 ,-C(O)N(R 21 )2, -N(R 21 )C(O)R 21 C is substituted with one or more substituents independently selected from =O and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)OR 21 -OC(O)R 21 ,-C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )S(O)2(R 21 ), -S(O)2R 21 -S(O)2N(R 21 )2, C substituted with one or more substituents independently selected from =O and -CN 3-6 Carbon rings and 3- to 6-membered heterorings Selected from.

[0128] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 17 Independently, hydrogen in each case; depending on the case, halogen, -OR 21 , -N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 C is substituted with one or more substituents independently selected from =O and -CN. 1-6 alkyl; and halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -N(R 21 )2, -C(O)R 21 ,-C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , =O and -CNC 3-6 Selected from carbon rings and 3- to 6-membered heterorings. In one embodiment, R 17 Independently, hydrogen and C are in each case. 1-6 Alkyl, C 3-6 Selected from carbocyclic and 3- to 6-membered heterocycles.

[0129] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 21 Each case is independent: hydrogen; C 1-4 Alkyl (sometimes halogen, hydroxyl, C) 3-6 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocyclic rings, where each C 3-6 Carbon rings and 3- to 6-membered heterorings may contain halogens, C 1-4 Alkyl and -C(O)N(R) 23 ) Substituted with one or more substituents independently selected from 2); and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 C substituted with one or more substituents independently selected from alkoxy and =O3-6 Carbon rings and 3- to 12-membered heterorings Selected from; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0130] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 21 Independently, hydrogen and C are in each case. 1-4 Alkyl, C 3-6 Selected from carbocyclic and 3- to 6-membered heterocycles (where C 3-6 Carbon rings and 3-6 membered heterorings are each C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the alkoxy; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0131] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12 A is selected from a carbon ring and a 3- to 12-membered heteroring, both of which are optionally substituted with one or more substituents. In one embodiment, C of A 3-12 The carbon rings and 3- to 12-membered heterocycles are selected from phenyl; pyridine; indan; chroman; benzodioxole; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole, all of which may be substituted with one or more substituents.

[0132] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6The carbon rings and 3- to 7-membered monocyclic heterocycles are selected, and both are optionally substituted with one or more substituents. In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbon rings and 3- to 12-membered heterocycles are selected from phenyl, pyridine, and pyrazole, and each is optionally substituted with one or more substituents.

[0133] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3-12 membered heterorings are polycyclic C 7-12 The carbon rings and 7-12 membered monocyclic heterocycles are selected, and both are optionally substituted with one or more substituents. In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbon rings and 3- to 12-membered heterorings are selected from indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; and 2',3'-dihydrospiro[cyclopropane-1,1'-indene], all of which may be substituted with one or more substituents.

[0134] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), the substituent present in the case of one or more A is Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings Selected from.

[0135] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), the substituent present in the case of one or more A is Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings Selected from.

[0136] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), the substituents present by A in the case of one or more A are: Halogen, -OR 17 , N(R 17 )2, -C(O)R 17 , -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2(R 17 ), =O, =S and -CN; C 1-6 Alkyl (sometimes halogen, -OR) 17 , -N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2(R 17 ), -S(O)R 17 , substituted with one or more substituents independently selected from =O and -CN); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings Selected from.

[0137] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), if A is one or more substituents present are halogens, -OR 17 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon ring and the 3-10 membered heteroring are each C 1-4 Alkyl, C 1-4 Selected from haloalkyl and substituted with one or more substituents independently selected from =O.

[0138] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12 Selected from carbocyclic and 3- to 12-membered heterocycles, in either case Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents selected from the following.

[0139] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12 Selected from carbon rings and 3- to 12-membered heterorings, both of which may be halogens;-OR 17 ;C which may be substituted with one or more substituents selected independently of halogens. 1-6 Alkyl; and in both cases halogen, C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 It is substituted with one or more substituents selected from carbon rings and 3- to 10-membered heterorings. In one embodiment, A is C 3-12 Selected from carbon rings and 3- to 12-membered heterorings, both of which may contain halogens, -OR 17 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10The carbon ring and the 3-10 membered heteroring are each C 1-4 Alkyl, C 1-4 It is substituted with one or more substituents selected from haloalkyl and =O (which are independently selected from one or more substituents). In one embodiment, R 17 Independently, hydrogen in each case; depending on the case, halogen, -OR 21 , -N(R 21 )2, -C(O)N(R 21 )2, -N(R 21 )C(O)R 21 C is substituted with one or more substituents independently selected from =O and -CN. 1-6 alkyl; and halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 21 , -N(R 21 )2, -C(O)R 21 ,-C(O)N(R 21 )2, -N(R 21 )C(O)R 21 , =O and -CNC 3-6 Selected from carbon rings and 3- to 6-membered heterorings. In one embodiment, R 17 Independently, hydrogen and C are in each case. 1-6 Alkyl, C 3-6 Selected from carbocyclic and 3- to 6-membered heterocycles.

[0140] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12 Selected from carbocyclic and 3-12 membered heterocycles, each optionally containing halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents selected from the following.

[0141] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is C 3-12Selected from carbocyclic and 3-12 membered heterocycles, each optionally containing halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents selected from the following.

[0142] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is selected from phenyl; pyridine; indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole, in any case Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17)2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0143] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is selected from phenyl; pyridine; indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole, in any case Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0144] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is selected from phenyl; pyridine; indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole, all of which may be halogens;-OR 17 ;C which may be substituted with one or more substituents selected independently of halogens. 1-6 Alkyl; and in both cases halogen, C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0145] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is selected from phenyl; pyridine; indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole, all of which may optionally contain halogens, -OR 17 , C 1-6 Alkyl, C1-6 Haloalkyl, C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon ring and the 3-10 membered heteroring are each C 1-4 Alkyl, C 1-4 (Substituted with one or more substituents independently selected from haloalkyl and =O) It is substituted with one or more substituents independently selected from the given molecule.

[0146] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is selected from phenyl; pyridine; indan; chroman; benzodioxole; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole, all of which may optionally contain halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0147] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is selected from phenyl; pyridine; indan; chroman; benzodioxole; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole, all of which may optionally contain halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0148] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, in either case Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0149] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, in either case Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0150] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, both of which may contain halogens, -OR 17 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon ring and the 3-10 membered heteroring are each C 1-4 Alkyl, C 1-4 (substituted with one or more substituents independently selected from haloalkyl and =O)

[0151] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbocyclic and 3- to 7-membered monocyclic heterocyclic compounds, each optionally containing halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0152] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbocyclic and 3- to 12-membered heterocycles are selected from phenyl, pyridine, and pyrazole, and all are used in the case of Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17)2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0153] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12The carbocyclic and 3- to 12-membered heterocycles are selected from phenyl, pyridine, and pyrazole, and all are used in the case of Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0154] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbocyclic and 3- to 12-membered heterocycles are selected from phenyl, pyridine, and pyrazole, and each may have a halogen, -OR 17 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon ring and the 3-10 membered heteroring are each C 1-4 Alkyl, C 1-4 (Substituted with one or more substituents independently selected from haloalkyl and =O) It is substituted with one or more substituents independently selected from the given molecule.

[0155] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbocyclic and 3-12 membered heterocycles are selected from phenyl, pyridine, and pyrazole, and each may contain halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0156] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3-12 membered heterorings are polycyclic C 7-12 Selected from carbocyclic and 7-12 membered polycyclic heterocycles, in either case Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17, -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0157] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3-12 membered heterorings are polycyclic C 7-12 Selected from carbocyclic and 7-12 membered polycyclic heterocycles, in either case Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0158] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3-12 membered heterorings are polycyclic C 7-12 Selected from carbon rings and 7-12 membered polycyclic heterocycles, both of which may contain halogens, -OR 17 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon ring and the 3-10 membered heteroring are each C 1-4 Alkyl, C 1-4 (Substituted with one or more substituents independently selected from haloalkyl and =O) It is substituted with one or more substituents independently selected from the given molecule.

[0159] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 Carbon rings and 3-12 membered heterorings are polycyclic C 7-12 Selected from carbocyclic and 7-12 membered polycyclic heterocycles, each may contain halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0160] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbon rings and 3- to 12-membered heterocycles are selected from indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; and 2',3'-dihydrospiro[cyclopropane-1,1'-indene], all of which may be: Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17 )2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )2, -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-OC(O)N(R 17 ) 2、 -C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )C(O)OR 17 , -N(R 17 )C(O)N(R 17)2, -N(R 17 )S(O)2(R 17 ), -S(O)R 17 -S(O)2R 17 -S(O)2N(R 17 )C substituted with one or more substituents independently selected from 2, -NO2, =O, and -CN 1-6 alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0161] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbon rings and 3- to 12-membered heterocycles are selected from indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; and 2',3'-dihydrospiro[cyclopropane-1,1'-indene], all of which may be used in some cases. Halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 -NO2, =O and -CN; Depending on the situation, halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)OR 17 -OC(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 C is substituted with one or more substituents independently selected from -NO2, =O, and -CN. 1-6alkyl; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles.

[0162] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbon rings and 3- to 12-membered heterorings are selected from indan; chroman; benzodioxol; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; and 2',3'-dihydrospiro[cyclopropane-1,1'-indene], all of which may contain halogens, -OR 17 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon ring and the 3-10 membered heteroring are each C 1-4 Alkyl, C 1-4 (substituted with one or more substituents independently selected from haloalkyl and =O)

[0163] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A's C 3-12 The carbon rings and 3- to 12-membered heterocycles are selected from indan; chroman; benzodioxole; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; and 2',3'-dihydrospiro[cyclopropane-1,1'-indene], all of which may contain halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0164] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is [ka] [ka] Selected from.

[0165] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), A is [ka] [ka] Selected from.

[0166] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), when A is selected from (ii), B is selected from (I), or when A is selected from (i), B is selected from (II): (I) Hydrogen, halogens and -CN or B and R 7 They become one C 3-6 Forms a carbon ring or a 3- to 6-membered heteroring; (II)-OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 and -S(O)2N(R 18 )2; C 3-12 Carbon rings and 3-12 membered heterorings [both depending on the case] Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3 and -CN; C 1-6 Alkyl (depending on the case: Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings [Substituted with one or more substituents independently selected from the original compound.]

[0167] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), when A is selected from (ii), B is selected from (I), or when A is selected from (i), B is selected from (II): (I) Hydrogen, halogens and -CN or B and R 7 They become one C 3-6 Forms a carbon ring or a 3- to 6-membered heteroring; (II)-OR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18, -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)2R 18 and -S(O)2N(R 18 )2; C 3-12 Carbon rings and 3- to 12-membered heterorings [both depending on the case: Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, =O and -CN; C 1-6 Alkyl (depending on the case: Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18-S(O)2R 18 -S(O)2N(R 18 )2, =O-CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 [Substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles.]

[0168] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), when A is selected from (ii), B is selected from (I), or when A is selected from (i), B is selected from (II): (I) Hydrogen and halogens; (II)-N(R 18 )2, -C(O)R 18 , -C(O)OR 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )S(O)2(R 18 ); C 3-12 Carbon rings and 3- to 12-membered heterorings [both depending on the case: Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18,-C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )S(O)2(R 18 ), -S(O)2R 18 , =O and -CN; C 1-6 Alkyl (depending on the case: Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 ,-C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )S(O)2(R 18 ), -S(O)2R 18 ,=O,-CN, and optionally halogens, C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-6 Carbon ring Substituted with one or more substituents independently selected from; and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings [Substituted with one or more substituents independently selected from the original compound.]

[0169] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), when A is selected from (ii), B is selected from (I), or when A is selected from (i), B is selected from (II): (I) Hydrogen and halogens; (II)-N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18)C(O)N(R 18 )2, -N(R 18 )S(O)2(R 18 ); and C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 Alkyl; and in all cases halogen and C 1-4 C is substituted with one or more substituents independently selected from alkyl groups. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from the original molecule.)

[0170] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), when A is selected from (ii), B is selected from (I), or when A is selected from (i), B is selected from (II): (I) Hydrogen and halogens; (II)-N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ).

[0171] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), when A is selected from (ii), B is selected from (I), or when A is selected from (i), B is selected from (II): (I) Hydrogen and halogens; (II)C 3-12 Carbon rings and 3- to 12-membered heterorings (both depending on the case): Halogen;-OR 18; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 Alkyl; and in all cases halogen and C 1-4 C is substituted with one or more substituents independently selected from alkyl groups. 3-10 Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from the original molecule.)

[0172] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from hydrogen, halogen, and -CN, or B and R 7 They become one C 3-6 It forms a carbon ring or a 3-6 membered heteroring. In one embodiment, B is selected from hydrogen and halogen or B and R 7 They become one C 3-6 It forms a carbon ring or a 3-6 membered heteroring. In one embodiment, B is selected from hydrogen and halogen or B and R 7 They become one C 3-6 A carbon ring is formed. In one embodiment, B is selected from hydrogen, halogen and -CN. In one embodiment, B is selected from hydrogen and halogen. In one embodiment, B is selected from hydrogen and halogen. In one embodiment, B is selected from hydrogen. In one embodiment, B is selected from halogen. In one embodiment, B and R 7 They become one C 3-6 It forms a carbon ring.

[0173] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is C 3-12 They are selected from carbocyclic and 3- to 12-membered heterocycles, and in both cases, they are substituted with one or more substituents.

[0174] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C3-12 The carbon ring and the 3-12 membered heteroring are each in their respective cases. Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 and = O; Depending on the situation, halogen, -OR 18 , -N(R 18 )2, =O, -CN, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles.

[0175] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 The carbon rings and 3- to 12-membered heterorings are, respectively, halogens;- OR 18 ; Depending on the case, halogen, OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 A carbon ring and a 3- to 10-membered heteroring, where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 It is substituted with one or more substituents that are independently selected from the alkyl group.

[0176] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is C3-12 Selected from carbocyclic and 3- to 12-membered heterocycles, in either case Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 , =O and -CN; Depending on the situation, halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , =O, -CN, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0177] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is C 3-12 Selected from carbon rings and 3- to 12-membered heterorings, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl) and (substituted with one or more substituents independently selected from. In one embodiment, B is C3-12 Selected from carbon rings and 3- to 12-membered heterorings, both possibly halogens; possibly halogens and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (Substituted with one or more substituents independently selected from the alkyl group) It is substituted with one or more substituents independently selected from the given molecule.

[0178] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each case is independent: hydrogen; C 1-6 Alkyl (depending on the case: Halogen, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 and -N(R 22 ) Substituted with one or more substituents independently selected from 2); and In both cases, halogen or C 1-6Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 Carbon rings and 3- to 10-membered heterorings Selected from.

[0179] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 In each case, hydrogen is used independently; in each case, halogen and C are used independently. 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 Alkyl; and in both cases halogen, C 1-6 Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 Selected from carbocyclic and 3- to 10-membered heterocycles.

[0180] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 22 Each case is independent: hydrogen; C 1-4 Alkyl (sometimes halogen, hydroxyl, C) 3-6 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocyclic rings, where each C 3-6 Carbon rings and 3- to 6-membered heterorings may contain halogens, C 1-4 Alkyl and -C(O)N(R) 23 ) Substituted with one or more substituents independently selected from 2); and In both cases, halogen or C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 C substituted with one or more substituents independently selected from alkoxy and =O 3-6 Carbon rings and 3- to 12-membered heterorings Selected from; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0181] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 22 Independently, hydrogen and C are in each case. 1-4 Alkyl, C 3-6 Selected from carbocyclic and 3- to 6-membered heterocycles (where C 3-6 Carbon rings and 3-6 membered heterorings are each C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the alkoxy; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0182] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 The carbon rings and 3- to 12-membered heterocycles are selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may be substituted with one or more substituents.

[0183] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 The components are selected from carbocyclic and 3- to 7-membered monocyclic heterocycles, and are optionally substituted with one or more substituents. In one embodiment, B is selected from phenyl and pyridinyl, and is optionally substituted with one or more substituents.

[0184] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is a bicyclic C 6-12The carbon rings and bicyclic 6-12 membered bicyclic heterocycles are selected, and each is optionally substituted with one or more substituents. In one embodiment, B is selected from naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, and each is optionally substituted with one or more substituents.

[0185] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), the substituents present by one or more of B are independently: Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3 and -CN; C 1-6 Alkyl (depending on the case: Halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18, -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 -S(O)2N(R 18 )2, -NO2, =O, =S, =N(R 18 ), -N3, -CN, C 3-6 It is substituted with one or more substituents independently selected from carbon rings and 3- to 6-membered heterorings. Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Selected from carbocyclic and 3- to 10-membered heterocycles.

[0186] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), the substituents present by one or more of B are independently: Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 , =O and -CN; Depending on the situation, halogen, -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , =O, -CN, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings Selected from.

[0187] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), the substituents present by B in the case of one or more are independently Halogen and -OR 18 ; Depending on the situation, halogen, OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (Substituted with one or more substituents independently selected from the alkyl group) Selected from.

[0188] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is C 3-12 Selected from carbon rings and 3- to 12-membered heterorings, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocyclic rings, where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4It is substituted with one or more substituents independently selected from alkyl groups; where R 18 Independently, hydrogen and C are in each case. 1-6 Alkyl and optionally halogen, C 1-6 Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 Selected from the carbocyclic ring.

[0189] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is C 3-12 Selected from carbocyclic and 3- to 12-membered heterocycles, each optionally containing halogens, trifluoromethyl, cyclopropyl, phenyl, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0190] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is C 3-12 Selected from carbocyclic and 3- to 12-membered heterocycles, each optionally containing halogens, trifluoromethyl, cyclopropyl, phenyl, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0191] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may include: Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 and = O; Depending on the situation, halogen, -OR 18 , -N(R 18 )2, =O, -CN, C3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0192] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (Substituted with one or more substituents independently selected from the alkyl group) It is substituted with one or more substituents independently selected from the given molecule.

[0193] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may be halogens; and may be halogens and C 3-6A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (Substituted with one or more substituents independently selected from the alkyl group) It is substituted with one or more substituents independently selected from the given molecule.

[0194] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl) and (where R 18 Independently, hydrogen and C are in each case. 1-6 Alkyl and optionally halogen, C 1-6 Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 Selected from the carbocyclic ring.

[0195] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may include halogen, trifluoromethyl, cyclopropyl, phenyl, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0196] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may include halogen, trifluoromethyl, cyclopropyl, phenyl, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0197] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, in either case Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 and = O; Depending on the situation, halogen, -OR 18 , -N(R 18 )2, =O, -CN, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0198] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0199] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbon rings and 3- to 7-membered monocyclic heterorings, both possibly halogens; and possibly halogens and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0200] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl) and (where R 18 Independently, hydrogen and C are in each case. 1-6 Alkyl and optionally halogen, C 1-6 Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 It is selected from the carbocyclic ring.

[0201] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B's C 3-12 Carbon rings and 3- to 12-membered heterorings are monocyclic C 3-6 Selected from carbocyclic and 3- to 7-membered monocyclic heterocyclic compounds, each optionally containing halogens, trifluoromethyl, cyclopropyl, phenyl, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0202] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl and pyridinyl, in either case Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 and = O; Depending on the situation, halogen, -OR 18 , -N(R 18 )2, =O, -CN, C3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0203] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl and pyridinyl, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0204] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl and pyridinyl, both of which may be halogens; and may be halogens and C. 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0205] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl and pyridinyl, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl) and (where R 18 Independently, hydrogen and C are in each case. 1-6 Alkyl and optionally halogen, C 1-6 Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 Selected from the carbocyclic ring.

[0206] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from phenyl and pyridinyl, and in each case, halogen, trifluoromethyl, cyclopropyl, phenyl [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0207] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is a bicyclic C 6-12Selected from carbocyclic and bicyclic 6-12 membered bicyclic heterocycles, in either case Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 and = O; Depending on the situation, halogen, -OR 18 , -N(R 18 )2, =O, -CN, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0208] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is a bicyclic C 6-12 Selected from carbon rings and bicyclic 6-12 membered bicyclic heterocycles, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0209] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is a bicyclic C 6-12 Selected from carbon rings and bicyclic 6-12 membered bicyclic heterocycles, both of which may be halogens; and may be halogens and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0210] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is a bicyclic C 6-12 Selected from carbon rings and bicyclic 6-12 membered bicyclic heterocycles, both of which may be halogens;-OR 18 ; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl) and substituted with one or more substituents independently selected from; where R 18 Independently, hydrogen and C are in each case. 1-6 Alkyl and optionally halogen, C 1-6 Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 Selected from the carbocyclic ring.

[0211] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is a bicyclic C 6-12Selected from carbocyclic and bicyclic 6-12 membered bicyclic heterocyclic compounds, each optionally containing halogens, trifluoromethyl, cyclopropyl, phenyl, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0212] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, in any case Halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 and = O; Depending on the situation, halogen, -OR 18 , -N(R 18 )2, =O, -CN, C 3-6 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles. 1-6 Alkyl (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl, C 1-4 Substituted with one or more substituents independently selected from haloalkyl and =O); and In both cases, halogen or C 1-4 Alkyl, C 1-4 C is substituted with one or more substituents independently selected from haloalkyl and =O. 3-10 Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from the given molecule.

[0213] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may be halogens;-OR 18; Depending on the case, halogen, -OR 18 and C 3-6 A carbon atom substituted with one or more substituents independently selected from the carbon ring. 1-6 alkyl; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0214] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which optionally contain halogens and C 3-6 Carbon ring; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl)

[0215] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman; each may be independently a halogen, -OR 18 and C 3-6 Carbon ring; and C 3-10 Carbon rings and 3-10 membered heterorings (where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-4 (substituted with one or more substituents independently selected from alkyl) and substituted with one or more substituents selected from; where R 18 Independently, hydrogen and C are in each case. 1-6 Alkyl and optionally halogen, C 1-6Alkyl, C 1-6 C is substituted with one or more substituents independently selected from haloalkyl groups. 3-10 Selected from the carbocyclic ring.

[0216] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is selected from naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, all of which may contain halogen, trifluoromethyl, cyclopropyl, phenyl, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0217] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is: [ka] Selected from.

[0218] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is [ka] Selected from.

[0219] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is -OR 18 , -SR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18, -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2, -N(R 18 )S(O)2(R 18 ), -S(O)R 18 -S(O)2R 18 and -S(O)2N(R 18 ) Selected from 2. In one embodiment, B is -OR 18 , -N(R 18 )2, -C(O)R 18 , -C(O)OR 18 -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ) is selected from. In one embodiment, B is -OR 18 , -N(R 18 )2, -OC(O)R 18 ,-OC(O)N(R 18 )2, -C(O)N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ) is selected from. In one embodiment, B is -OR 18 , -N(R 18 )2, -OC(O)R 18 ,-OC(O)N(R 18 )2, -N(R18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ) will be selected from.

[0220] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is -OR 18 , -N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ) is selected from. In one embodiment, B is -N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2, -N(R 18 )C(S)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ) is selected from. In one embodiment, B is -N(R 18 )2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)OR 18 , -N(R 18 )C(O)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ) is selected from. In one embodiment, B is -N(R 18)2, -N(R 18 )C(O)R 18 , -N(R 18 )C(O)N(R 18 )2 and -N(R 18 )S(O)2(R 18 ) is selected from. In one embodiment, B is -N(R 18 )2. In one embodiment, B is -N(R 18 )C(O)R 18 Therefore, in one embodiment, B is -N(R 18 )C(O)N(R 18 )2. In one embodiment, B is -N(R 18 )S(O)2(R 18 )

[0221] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each case is independent: hydrogen; C 1-6 Alkyl (depending on the case: Halogen, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 and -N(R 22 ) Substituted with one or more substituents independently selected from 2); and C 3-10 Carbon rings and 3- to 10-membered heterorings (both depending on the case): Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 , -N(R 22 )C(O)N(R 22 )2, -N(R 22 )C(S)N(R 22 )2, -N(R 22 )S(O)2(R 22 ), -S(O)R 22 -S(O)2R 22 -S(O)2N(R 22 )2, -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-6 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocyclic rings; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 (Substituted with one or more substituents independently selected from the haloalkyl group.) Selected from.

[0222] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Independently, hydrogen and C in each case 1-6 Alkyl (depending on the case: Halogen, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22, -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. Here, C 3-10 The carbon rings and 3- to 10-membered heterorings may each contain halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 and -N(R 22 Selected from (which are substituted with one or more substituents independently selected from 2).

[0223] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Independently, hydrogen in each case and halogen in each case, -OR 22 , -N(R 22 )2, =O, -CN, C 3-10 C is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocyclic rings. 1-6 Selected from alkyl groups; where C 3-10 The carbon rings and 3- to 10-membered heterorings are, respectively, halogens and C 1-6 It is substituted with one or more substituents independently selected from the alkyl group.

[0224] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 22 Each case is independent: hydrogen; C 1-4 Alkyl (sometimes halogen, hydroxyl, C) 3-6 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocyclic rings, where each C 3-6Carbon rings and 3- to 6-membered heterorings may contain halogens, C 1-4 Alkyl and -C(O)N(R) 23 ) Substituted with one or more substituents independently selected from 2); and C 3-6 Carbon rings and 3-12 member heterorings (both can contain halogens, C) 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 (Substituted with one or more substituents independently selected from alkoxy and =O) Selected from; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0225] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 22 Independently, hydrogen and C are in each case. 1-4 Alkyl, C 3-6 Selected from carbocyclic and 3- to 6-membered heterocycles, where C 3-6 Carbon rings and 3-6 membered heterorings are each C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the alkoxy; and R 23 Independently, hydrogen and C in each case 1-4 Selected from alkyl groups.

[0226] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Independently in each case: hydrogen, C 3-10 Selected from carbocyclic and 3- to 10-membered heterocycles, where R 18 Each C 3-10 The carbon rings and 3- to 10-membered heterorings are optionally substituted with one or more substituents. In one embodiment, R 18 Each C 3-10The carbocyclic and 3- to 10-membered heterocycles are independently each substituted with hydrogen; and selected from pyrrolidine, piperidine, phenyl, indoline, bicyclo[2.2.2]octane, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, thieno[2,3-d]pyrimidine oxide, and cyclopropyl, each optionally substituted with one or more substituents.

[0227] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3-10 membered heteroring are independently monocyclic C in each case. 3-6 A carbon ring and a 3- to 7-membered monocyclic heterocycle are selected, and both are optionally substituted with one or more substituents. In one embodiment, R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocyclic rings are independently selected in each case from pyrrolidine, piperidine, phenyl, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, and cyclopropyl, and each is optionally substituted with one or more substituents. In one embodiment, R 18 Each of these is independently hydrogen; and selected from pyrrolidine, piperidine, phenyl, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, and cyclopropyl, each of which is optionally substituted with one or more substituents.

[0228] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3- to 10-membered heteroring are independently bicyclic C in each case. 6-10 A carbon ring and a bicyclic 6-10 membered bicyclic heterocycle are selected, and both are optionally substituted with one or more substituents. In one embodiment, R 18 Each C 3-10The carbon ring and the 3- to 10-membered heteroring are independently selected in each case from indoline, bicyclo[2.2.2]octane, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indane, and thieno[2,3-d]pyrimidine oxide, each of which is optionally substituted with one or more substituents. In one embodiment, R 18 Each is independently hydrogen; and selected from indoline, bicyclo[2.2.2]octane, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indane, and thieno[2,3-d]pyrimidine oxide, each of which is optionally substituted with one or more substituents.

[0229] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 C 3-10 The carbon ring and the 3-10 membered heteroring each independently form a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -N(R 22 )2, -C(O)R 22 ,-C(O)N(R 22 )2, -N(R 22 )C(O)R 22 -S(O)2R 22 , =O, -CN, C 3-6 Carbon rings and 3-6 membered heterorings (where C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 (substituted with one or more substituents independently selected from haloalkyl) optionally substituted with one or more substituents selected from. In one embodiment, R 18 C 3-10 The carbon ring and the 3-10 membered heteroring each independently form a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -N(R) 22 )2, -C(O)R 22 ,-C(O)N(R 22)2, -S(O)2R 22 ,=O,C 3-6 Carbon rings and 3-6 membered heterorings (where C 3-6 The carbon rings and 3- to 6-membered heterorings are, respectively, halogens and C 1-4 (Optionally substituted with one or more substituents independently selected from haloalkyl)

[0230] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 C 3-10 The carbocyclic and 3-10 membered heterocycles are, in each case, independently halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, -NH2, =O, [ka] It is optionally substituted with one or more substituents selected from. In one embodiment, R 18 C 3-10 The carbocyclic and 3-10 membered heterocycles are, in each case, independently halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, -NH2, =O, [ka] It may be substituted with one or more substituents selected from the following.

[0231] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each case is independent: Hydrogen, C 3-10 Carbon rings and 3- to 10-membered heterorings Selected from, here, R 18 Each C 3-10 In each case, the carbocyclic and 3- to 10-membered heterocyclic rings are: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 , -N(R 22 )C(O)N(R 22 )2, -N(R 22 )C(S)N(R 22 )2, -N(R 22 )S(O)2(R 22 ), -S(O)R 22 -S(O)2R 22 -S(O)2N(R 22 )2, -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-6 Optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0232] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each case is independent: Hydrogen, C 3-10 Carbon rings and 3- to 10-membered heterorings Selected from, here, R 18 Each C 3-10 In each case, the carbocyclic and 3- to 10-membered heterocyclic rings are: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22)2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 -S(O)2R 22 -S(O)2N(R 22 )2, =O, -CN, C 3-6 Optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0233] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Independently in each case: hydrogen, C 3-10 Selected from carbocyclic and 3- to 10-membered heterocycles, where R 18 Each C 3-10 In each case, the carbocyclic and 3- to 10-membered heterocyclic rings are: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -N(R) 22 )2, -C(O)R 22 ,-C(O)N(R 22 )2, -S(O)2R 22 , C 3-6 Optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 6-membered heterocycles; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0234] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Independently in each case: hydrogen, C 3-10Selected from carbocyclic and 3- to 10-membered heterocycles, where R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocycles are selected from pyrrolidine, piperidine, phenyl, indoline, bicyclo[2.2.2]octane, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, thieno[2,3-d]pyrimidine oxide, and cyclopropyl, all of which may be used in some cases. Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -SR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 , -N(R 22 )C(O)N(R 22 )2, -N(R 22 )C(S)N(R 22 )2, -N(R 22 )S(O)2(R 22 ), -S(O)R 22 -S(O)2R 22 -S(O)2N(R 22 )2, -NO2, =O, =S, =N(R 22 ), -N3, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0235] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocycles are selected from pyrrolidine, piperidine, phenyl, indoline, bicyclo[2.2.2]octane, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, thieno[2,3-d]pyrimidine oxide, and cyclopropyl, all of which may be used in some cases. Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 -S(O)2R 22 -S(O)2N(R 22 )2, =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0236] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10The carbocyclic and 3- to 10-membered heterocycles are selected from pyrrolidine, piperidine, phenyl, indoline, bicyclo[2.2.2]octane, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, thieno[2,3-d]pyrimidine oxide, and cyclopropyl, all of which may be used in some cases. Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -N(R) 22 )2, -C(O)R 22 ,-C(O)N(R 22 )2, -S(O)2R 22 , C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0237] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocycles are selected from pyrrolidine, piperidine, phenyl, indoline, bicyclo[2.2.2]octane, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, thieno[2,3-d]pyrimidine oxide, and cyclopropyl, all of which may include halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, -NH2, =O, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0238] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3-10 membered heteroring are independently monocyclic C in each case. 3-6 Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, in each case Hydrogen, C 3-10 It is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles, where R 18 Each C 3-10 In each case, the carbocyclic and 3- to 10-membered heterocyclic rings are: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 -S(O)2R 22 -S(O)2N(R 22 )2, =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings Optionally substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0239] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3-10 membered heteroring are independently monocyclic C in each case. 3-6Selected from carbon rings and 3- to 7-membered monocyclic heterocycles, in each case Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -N(R) 22 )2, -C(O)R 22 ,-C(O)N(R 22 )2, -S(O)2R 22 , C 3-6 Carbon rings and 3- to 6-membered heterorings Optionally substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0240] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3-10 membered heteroring are independently monocyclic C in each case. 3-6 Selected from carbocyclic and 3- to 7-membered monocyclic heterocyclic compounds, each containing halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, -NH2, =O, in each case. [ka] It is optionally substituted with one or more substituents independently selected from the given molecule.

[0241] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocycles are independently selected in each case from pyrrolidine, piperidine, phenyl, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, and cyclopropyl, and each in each case Hydrogen, C 3-10 It is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles, where R 18Each C 3-10 In each case, the carbocyclic and 3- to 10-membered heterocyclic rings are: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 -S(O)2R 22 -S(O)2N(R 22 )2, =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings Optionally substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0242] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocycles are independently selected in each case from pyrrolidine, piperidine, phenyl, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, and cyclopropyl, and each in each case Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -N(R) 22 )2, -C(O)R 22 ,-C(O)N(R 22 )2, -S(O)2R 22 , C 3-6 Carbon rings and 3- to 6-membered heterorings Optionally substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0243] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3-10 membered heterocycles are independently selected in each case from pyrrolidine, piperidine, phenyl, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, and cyclopropyl, and in each case halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, -NH2, =O, [ka] It is optionally substituted with one or more substituents independently selected from the given molecule.

[0244] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3- to 10-membered heteroring are independently bicyclic C in each case. 6-10 Selected from carbon rings and bicyclic 6-10 membered bicyclic heterocycles, in each case Hydrogen, C 3-10 It is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles, where R 18 Each C 3-10 In each case, the carbocyclic and 3- to 10-membered heterocyclic rings are: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22)2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 -S(O)2R 22 -S(O)2N(R 22 )2, =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings Optionally substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0245] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3- to 10-membered heteroring are independently bicyclic C in each case. 6-10 Selected from carbon rings and bicyclic 6-10 membered bicyclic heterocycles, in each case Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -N(R) 22 )2, -C(O)R 22 ,-C(O)N(R 22 )2, -S(O)2R 22 , C 3-6 Carbon rings and 3- to 6-membered heterorings Optionally substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0246] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbon ring and the 3- to 10-membered heteroring are independently bicyclic C in each case.6-10 Selected from carbocyclic and bicyclic 6-10 membered bicyclic heterocyclic compounds, each containing halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, -NH2, =O, in each case. [ka] It is optionally substituted with one or more substituents independently selected from the given molecule.

[0247] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocycles are independently selected in each case from indoline, bicyclo[2.2.2]octane, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, and thieno[2,3-d]pyrimidine oxide, each in which case: Hydrogen, C 3-10 It is substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocyclic rings, where R 18 Each C 3-10 In each case, the carbocyclic and 3- to 10-membered heterocyclic rings are: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR 22 , -N(R 22 )2, -C(O)R 22 , -C(O)OR 22 -OC(O)R 22 ,-OC(O)N(R 22 )2, -C(O)N(R 22 )2, -N(R 22 )C(O)R 22 , -N(R 22 )C(O)OR 22 -S(O)2R 22 -S(O)2N(R 22 )2, =O, -CN, C 3-6 Carbon rings and 3- to 6-membered heterorings Optionally substituted with one or more substituents independently selected from; Here, C3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0248] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3- to 10-membered heterocycles are independently selected in each case from indoline, bicyclo[2.2.2]octane, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, and thieno[2,3-d]pyrimidine oxide, each in which case: Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -N(R) 22 )2, -C(O)R 22 ,-C(O)N(R 22 )2, -S(O)2R 22 , C 3-6 Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C 3-6 The carbon rings and 3- to 6-membered heterorings may each contain halogens, C 1-4 Alkyl and C 1-4 It is substituted with one or more substituents independently selected from the haloalkyl group.

[0249] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), R 18 Each C 3-10 The carbocyclic and 3-10 membered heterocycles are independently selected in each case from indoline, bicyclo[2.2.2]octane, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, and thieno[2,3-d]pyrimidine oxide, each depending on the case: halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, -NH2, =O, [ka] It is substituted with one or more substituents independently selected from the given molecule.

[0250] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is [ka] [ka] Selected from.

[0251] In one embodiment, for a compound or salt of formula (Ia), (IIa), or (IIIa), B is [ka] [ka] Selected from.

[0252] In one embodiment, the compound or salt of formula (I), (II), or (III) is selected from the compounds in Table 1 below. [Table 1] [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] Table 8 Table 9 Table 10 Table 11 Table 12 Table 13 Table 14 Table 15 Table 16 Table 17 Table 18 Table 19 Table 20 Table 21 Table 22 Table 23 Table 24

[0253] Synthesis method Figure 1 shows the synthesis of intermediate 10. Cyclic ester 3 is obtained by condensation of pyridylaldehyde 1 and ketoester 2 in the presence of pyrrolidine in sulfuric acid, and this is reduced under conventional conditions to obtain crude pyridyl ester 4. Boc derivative 5 is obtained by protection of the free amine, and this is reduced with lithium borohydride to obtain alcohol 6. Crude aldehyde 7 is obtained by Parik-Derling oxidation of alcohol 6, and this is condensed with amine 8 under reducing conditions to obtain 3-pyridyl ester 9. Crude lithium salt 10 is obtained by hydrolysis of ester 9.

[0254] Figure 2 shows the synthesis of the compound of formula (VII). Aldehyde 11 is condensed with malonic acid 12 in the presence of ammonium formate to obtain β-amino acid 13, which is then esterified to obtain β-aminoester 14. β-aminoester amide 15 is obtained by the reaction of β-aminoester 14 with compound 10, and this is deprotected to obtain the compound of formula (VII).

[0255] Figure 3 shows the separate synthesis of the compound of formula (VII). Compound 21 is obtained by cross-coupling of an aryl halide and a transition metal compound, and after acid deprotection, it is reacted with compound 10 to obtain esteramide 22, which is then deprotected overall to obtain the compound of formula (VII).

[0256] Figure 4 shows the synthesis of the compound of formula (VIII). Nitrile 28 is reacted with dimethyl carbonate 29 to obtain ester 30. Reduction of the nitrile and protection of the amine yield β-aminoester 31, which is then deprotected to obtain amine salt 32. Reaction of amine salt 32 with compound 10 yields esteramide 33, which is then deprotected to obtain the compound of formula (VIII).

[0257] Figure 5 shows the separate synthesis of the compound of formula (VIII). Compound 43 is obtained by cross-coupling of aryl halide 42 with a transition metal compound, and this is deprotected to obtain compound 44. Compound 44 is obtained by reaction of compound 44 with compound 10 to obtain esteramide 45, which is then deprotected overall to obtain the compound of formula (VIII).

[0258] Figure 6 shows the synthesis of amides and sulfonamides of formula (VIII). By using the reaction of free amine 51 under various conditions, amines, amides, urea, or sulfonamides 52 can be obtained, which are then deprotected to obtain the amine salt 53. The reaction of the amine salt 53 with compound 10 yields the esteramide 45, which is then deprotected to obtain the compound of formula (VIII).

[0259] Next, as shown in Figure 7, compound 62 is acylated or reductively alkylated with substituted piperidinyl ester 63 to obtain compound 64. Hydrolysis of compound 64 yields lithium salt 65, which is then reacted with ester 66 to obtain compound 67, and this is deprotected as a whole to obtain compound 68.

[0260] Those skilled in the art will recognize that many other synthetic routes can be employed to provide compounds of formulas (I)–(VIII) and (Ia)–(IIIa). Therefore, the methods described in Figures 1–7 should be considered representative, not comprehensive.

[0261] How to use Methods are provided for the treatment, prevention, or symptom relief of medical disorders in patients requiring treatment, such as idiopathic pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, myositis-associated interstitial lung disease, systemic lupus erythematosus-associated interstitial lung disease, rheumatoid arthritis, associated interstitial lung disease, diabetic nephropathy, focal segmental glomerulosclerosis, chronic kidney disease, non-alcoholic fatty liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, solid tumors, hematological malignancies, organ transplantation, Alport syndrome, interstitial lung disease, radiation-induced fibrosis, bleomycin-induced fibrosis, asbestos-induced fibrosis, influenza-induced fibrosis, coagulation-induced fibrosis, vascular injury-induced fibrosis, aortic stenosis, and cardiac fibrosis. In carrying out this method, a therapeutically effective amount of the compound of formula (I) and / or its pharmaceutical composition is administered to the patient having the disorder or condition.

[0262] Examples of solid tumors (e.g., sarcomas, carcinomas, and lymphomas) that can be treated with the compound of formula (I) and its pharmaceutical compositions include, for example, Ewing's sarcoma, rhabdomyosarcoma, osteosarcoma, myelosarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, soft tissue sarcoma, non-small cell lung cancer, small cell lung cancer, bronchial cancer, prostate cancer, breast cancer, pancreatic cancer, gastrointestinal cancer, colon cancer, rectal cancer, colon carcinoma, colorectal adenoma, thyroid cancer, liver cancer, intrahepatic cholangiocarcinoma, hepatocellular carcinoma, adrenal cancer, gastric cancer, gastric cancer, glioma (e.g., adult, pediatric brainstem, pediatric astrocytoma, pediatric optic tract and hypothalamus), glioblastoma, endometrial cancer, melanoma, kidney cancer, renal pelvis cancer, bladder cancer, uterine cancer, cervical cancer, vaginal cancer, ovarian cancer, multiple myeloma, esophageal cancer, and brain cancer (e.g., brainstem glioma, cerebellar astrocytoma). Cytoplasm, cerebral astrocytoma / malignant glioma, ependymoma, medulloblastoma, supratentorial cerebellar primitive neuroectodermal tumor, optic tract and hypothalamic glioma), lip and oral cavity and pharynx, larynx, small intestine, melanoma, choriocolonic adenoma, neoplasms, epithelial neoplasms, lymphoma (e.g., AIDS-related, Burkitt, cutaneous T-cell, Hodgkin, non-Hodgkin and primary central nervous system), breast cancer, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, tumor diseases including solid tumors, head and neck tumors, polycythemia vera, essential thrombocythemia, myelofibrosis with myelogenesis, Waldenström macroglobulinemia, adrenal cortical carcinoma, AIDS-related cancer, pediatric cerebellar astrocytoma, pediatric cerebellar astrocytoma, basal cell carcinoma, extrahepatic cholangiocarcinoma, malignant fibrous histiocytomaBone cancer, bronchial adenoma / carcinoid, carcinoid tumor, gastrointestinal carcinoid tumor, primary central nervous system, cerebellar astrocytoma, childhood cancer, ependymoma, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic cholangiocarcinoma, intraocular melanoma, retinoblastoma, gallbladder cancer, gastrointestinal carcinoid tumor, germ cell tumor (e.g., extracranial, extragonadal, and ovarian), pregnancy trophoblastoma, hepatocellular carcinoma, hypopharyngeal cancer, hypothalamic and optic nerve glioma, islet cell carcinoma (endocrine pancreas), laryngeal cancer, malignant fibrous histiocytoma / osteosarcoma of bone, medulloblastoma, mesothelioma, metastasis of unknown primary origin This includes squamous cell carcinoma of the neck, multiple endocrine neoplasia syndrome, multiple myeloma / plasmacytic neoplasm, mycosis fungoides, nasal and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, oral cancer, oropharyngeal cancer, ovarian epithelial carcinoma, ovarian germ cell tumor, low-grade ovarian tumor, islet cell pancreatic cancer, parathyroid cancer, pheochromocytoma, pineoblastoma, pituitary tumor, pleuropulmonary blastoma, ureteral transitional cell carcinoma, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, Sézary syndrome, non-melanoma skin cancer, Merkel cell carcinoma, squamous cell carcinoma, testicular cancer, thymoma, pregnancy trophoblastoma, and Wilms' tumor.

[0263] Examples of hematological malignancies (e.g., sarcomas, carcinomas, and lymphomas) that can be treated with compounds of formula (I) and their pharmaceutical compositions include, for example, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphoblastic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma.

[0264] Also provided herein is a method for inhibiting αVβ6 integrin in a patient. In carrying out this method, a therapeutically effective amount of the compound of formula (I) or a pharmaceutical composition thereof is administered to a patient having the disorder or condition.

[0265] Also provided herein is a method for inhibiting αVβ1 integrin in a patient. In carrying out this method, a therapeutically effective amount of the compound of formula (I) or a pharmaceutical composition thereof is administered to a patient having the disorder or condition.

[0266] Also provided herein is a method for inhibiting TGFβ activation in cells. In carrying out this method, an effective amount of the compound or formula (I) or its pharmaceutical composition is administered to a patient having the disorder or condition.

[0267] Composition and administration method The compositions provided herein comprise one or more therapeutically effective amounts of the compounds provided herein and a medium useful for treating, preventing, or alleviating the symptoms of one or more of the diseases or disorders described herein. The medium suitable for administering the compounds provided herein includes any carrier known to those skilled in the art to be suitable for a particular method of administration. Furthermore, the compounds may be formulated as sole active ingredients in the composition or in combination with other active ingredients.

[0268] The composition comprises one or more of the compounds provided herein. In some embodiments, the compounds are formulated into solutions, suspensions, tablets, disintegrating tablets, pills, capsules, powders, sustained-release formulations or elixirs for oral administration, or sterile solutions or suspensions for non-enteral administration, as well as suitable formulations for topical administration, transdermal administration, and oral inhalation via nebulizers, pressurized metered-dose inhalers and dry powder inhalers. In some embodiments, the compounds are formulated into compositions using techniques and methods well known in the art (see, for example, Ansel, Introduction to Pharmaceutical Dosage Forms, Seventh Edition (1999)).

[0269] In a composition, one or more compounds or derivatives thereof at an effective concentration are mixed with a suitable medium. The compounds may be derivatized before formulation as described above to the corresponding salts, esters, enol ethers or esters, acetals, ketals, orthoesters, hemiacetals, hemiketals, acids, bases, solvates, ion pairs, hydrates, or prodrugs. The concentration of the compounds in the composition is effective for delivering an amount that, upon administration, treats, prevents, or alleviates one or more symptoms of the disease or disorder described herein. In some embodiments, the composition is formulated for a single dose. To formulate the composition, a weight fraction of the compounds is dissolved, suspended, dispersed, or otherwise mixed in a selected medium at an effective concentration that alleviates, prevents, or reduces one or more symptoms of the treated condition.

[0270] The active compound is included in the medium in an amount sufficient to exert a therapeutically beneficial effect without causing undesirable side effects in the treated patient. The therapeutically effective concentration can be empirically predicted by testing the compound in in vitro and in vivo systems well known to those skilled in the art, and then the dose for humans is extrapolated therefrom. The human dose is then typically fine-tuned in clinical trials and titrated for response.

[0271] The concentration of the active compound in the composition depends on the absorption, inactivation, and excretion rates of the active compound, the physicochemical characteristics of the compound, the administration schedule and dosage, and other factors known to those skilled in the art. For example, the amount delivered is sufficient to alleviate one or more symptoms of the disease or disorder described herein.

[0272] When the solubility of a compound is insufficient, methods for solubilizing the compound can be used, such as liposomes, prodrugs, complex formation / chelation, nanoparticles or emulsions or tertiary template formation. Such methods are known to those skilled in the art, and include the use of cosolvents such as dimethyl sulfoxide (DMSO) and tween. (登録商標)This includes, but is not limited to, the use of surfactants or surface modifiers, complexing agents such as cyclodextrins, or dissolution by ionization enhancement (i.e., dissolution in aqueous sodium bicarbonate). Derivatives of compounds, such as prodrugs of compounds, may also be used in the formulation of effective compositions.

[0273] After mixing or adding compounds, the resulting mixture may be a solution, suspension, emulsion, or the like. The form of the resulting mixture depends on several factors, including the intended method of administration and the solubility of the compound in the chosen medium. The effective concentration, which is sufficient to alleviate the symptoms of the disease, disorder, or condition being treated, can be determined empirically.

[0274] The compositions are provided for administration to humans and animals in dosage forms appropriate to the indication, including dry powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), nebulizers, tablets, capsules, pills, sublingual tapes / biodegradable strips, tablets or capsules, powders, granules, lozenges, lotions, ointments, suppositories, fast melts, transdermal patches or other transdermal application devices / formulations, sterile non-enteral solutions or suspensions, and oral solutions or suspensions and oil-water emulsions, containing appropriate amounts of the compound or its derivatives. In some embodiments, the therapeutically active compounds and their derivatives are formulated and administered in unit or multi-dosage forms. As used herein, unit dose forms refer to physically separated units that are suitable for human and animal subjects and individually packaged, as known in the art. Each unit dose contains a predetermined amount of the therapeutically active compound sufficient to produce the desired therapeutic effect, along with the necessary medium. Examples of unit dose forms include ampoules and syringes and individually packaged tablets or capsules. A unit dose form may be administered in part or in parts. A multiple dose form is multiple identical unit dosage forms packaged in a single container, administered in separate unit dose forms. Examples of multiple dose forms include vials, bottles of tablets or capsules, or pints or gallons. Thus, a multiple dose form is multiple unit doses that are not packaged separately.

[0275] Liquid compositions can be prepared by dissolving, dispersing, or otherwise mixing the specified active compounds and any adjuvants in a medium such as water, saline solution, aqueous dextrose, glycerol, glycol, or ethanol, thereby forming solutions or suspensions, colloidal dispersions, emulsions, or liposome formulations. Optionally, the administered composition may also contain trace amounts of non-toxic auxiliary substances such as wetting agents, emulsifiers, solubilizers, pH buffers, etc., such as acetate, sodium citrate, cyclodextrin derivatives, sorbitan monolaurate, sodium triethanolamine acetate, triethanolamine oleate, and other such agents.

[0276] The actual methods for preparing such dosage forms are known or obvious to those skilled in the art; see, for example, Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa., 15th Edition, 1975 or any subsequent edition.

[0277] Dosage forms or compositions can be prepared in which the active ingredient is present in an amount ranging from 0.005% to 100%, with the remainder being a medium or carrier. Methods for preparing these compositions are known to those skilled in the art. The intended compositions may contain the active ingredient in an amount ranging from 0.001% to 100%, in one embodiment from 0.1% to 95%, and in other embodiments from 0.4% to 10%.

[0278] In one embodiment, the composition is a lactose-free composition containing additives well known in the art and described, for example, in the United States Pharmacopeia (USP) 25-NF20 (2002). Generally, lactose-free compositions contain equal amounts of the active ingredient, binders / fillers, and lubricants. Specific lactose-free dosage forms contain the active ingredient, microcrystalline cellulose, alpha-starch, and magnesium stearate.

[0279] Furthermore, anhydrous compositions and dosage forms containing active ingredients are provided, as water can accelerate the decomposition of certain compounds. For example, the addition of water (e.g., 5%) is widely accepted as a means of mimicking long-term storage to determine characteristics such as shelf life or the stability of a formulation over time. See, for example, Jens T. Carstensen, Drug Stability: Principles & Practice, 2d. Ed., Marcel Dekker, NY, NY, 1995, pp. 379-80. In effect, water and heat accelerate the decomposition of certain compounds. Therefore, the effect of water on a formulation can be significantly influenced, as moisture and / or humidity are commonly encountered during the manufacture, handling, packaging, storage, transport, and use of the formulation.

[0280] The anhydrous compositions and dosage forms provided herein may be manufactured using anhydrous or low-moisture-containing components and low-moisture or low-humidity conditions.

[0281] Anhydrous compositions are prepared and stored in such a way that their anhydrous properties are maintained. Therefore, anhydrous compositions are packaged using substances known to prevent exposure to water, so that they may be included in suitable formulation kits. Examples of suitable packaging include, but are not limited to, sealed foil, plastic, unit dose containers (e.g., vials), blister packs, and strip packs.

[0282] Oral dosage forms are solid, gel, or liquid. Solid dosage forms include tablets, capsules, granules, and powders. Types of oral tablets include compressed, chewable lozenges, and tablets, which may be enteric coated, sugar coated, or film coated. Capsules may be hard or soft gelatin capsules, while granules and powders may be in non-foaming or effervescent forms combined with other components known to those skilled in the art.

[0283] In one embodiment, the formulation is a solid dosage form, such as a capsule or tablet. Tablets, pills, capsules, lozenges, etc., may contain one or more of the following components or compounds of similar properties: binders; lubricants; diluents; flow enhancers; disintegrants; colorants; sweeteners; flavorings; wetting agents; enteric coatings; film coatings and release modifiers. Examples of binders include microcrystalline cellulose, methylparaben, polyalkylene oxides, tragacanth gum, glucose solution, gum arabic viscosa, gelatin solution, sugar solution, polyvinylpyrrolidine, povidone, crospovidone, sucrose, and starch and starch derivatives. Lubricants include talc, starch, magnesium / calcium stearate, clubmoss, and stearic acid. Diluents include, for example, lactose, sucrose, trehalose, lysine, leucine, lecithin, starch, kaolin, salts, mannitol, and dicalcium phosphate. Flow enhancers include, but are not limited to, colloidal silicon dioxide. Disintegrants include croscarmellose sodium, starch glycolate sodium, alginic acid, corn starch, potato starch, bentonite, methylcellulose, agar, and carboxymethylcellulose. Colorants include, for example, approved and certified water-soluble FD and C dyes, mixtures thereof; and water-insoluble FD and C dyes suspended in alumina hydrate and high-performance coloring or anti-counterfeiting color / milky white additives known to those skilled in the art. Sweeteners include artificial sweeteners such as sucrose, lactose, mannitol, and saccharin, and several spray-dried flavorings. Flavorings include natural flavorings extracted from plants such as fruits, and synthetic blends of compounds that produce pleasant sensations or mask unpleasant tastes, such as, but are not limited to, peppermint and methyl salicylate. Humectants include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate, and polyoxyethylene lauryl ether. The enteric coating contains fatty acids, fats, waxes, shellac, ammonia-treated shellac, and cellulose phthalate acetate. The film coating contains hydroxyethylcellulose, sodium carboxymethylcellulose, polyethylene glycol 4000, and cellulose phthalate acetate.The release modifier is Eudragit. (登録商標) This includes polymers such as series and cellulose esters.

[0284] The compound or its derivatives may be provided in a composition that protects against the acidic environment of the stomach. For example, the composition can be formulated into an enteric coating that retains the entire compound in the stomach and releases the active compound in the intestines. The composition may also be formulated in combination with acid-fast or other such components.

[0285] When the unit dosage form is a capsule, in addition to the above-mentioned type of substance, it may contain a liquid carrier such as fatty oil. Furthermore, the unit dosage form may contain various other substances that modify the physical form of the administration unit, such as sugar coatings and other enteric coatings. The compound may also be administered as an ingredient in elixirs, suspensions, syrups, wafers, sprinkles, chewing gums, etc. In addition to the active compound, the syrup may contain sucrose as a sweetener, preservatives, pigments and colorants, and flavorings.

[0286] The active substance may be mixed with other active substances that do not interfere with the desired effect, or substances that complement the desired effect, such as acid fasteners, H2 blockers, and diuretics. The active ingredient is the compound or its derivatives described herein. High concentrations of the active ingredient up to approximately 98% by weight may be present.

[0287] In all embodiments, tablet and capsule formulations may be coated as is known to those skilled in the art to modify or prolong the dissolution of the active ingredient. For example, they may be coated with conventional enteric digestible coatings such as phenyl salicylate, wax, and cellulose phthalate acetate.

[0288] Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions reconstituted from non-effervescent granules, and / or effervescent formulations reconstituted from suspensions and effervescent granules. Aqueous solutions include, for example, elixirs and syrups. Emulsions are oil-in-water or water-in-oil.

[0289] Elixirs are clear, sweet-tasting hydroalcoholic preparations. The media used in elixirs include a solvent. Syrups are concentrated aqueous solutions of sugars, such as sucrose, and may contain preservatives. Emulsions are two-phase systems in which one liquid is dispersed in the other liquid in the form of small spheres. The carriers used in emulsions are non-aqueous liquids, emulsifiers, and preservatives. Suspensions use suspending agents and preservatives. Permitted substances used in non-foaming granules converted into liquid oral dosage forms include diluents, sweeteners, and wetting agents. Permitted substances used in foaming granules converted into liquid oral dosage forms include organic acids and carbon dioxide sources. Colorants and flavorings are used in all of the above dosage forms.

[0290] Solvents include glycerin, sorbitol, ethyl alcohol, and syrup. Examples of preservatives include glycerin, methyl and propylparabens, benzoic acid, sodium benzoate, and alcohol. Examples of non-aqueous liquids used in emulsions include mineral oil and cottonseed oil. Examples of emulsifiers include gelatin, acacia, tragacanth, bentonite, and surfactants, such as polyoxyethylene sorbitan monooleate. Suspensioning agents include sodium carboxymethylcellulose, pectin, tragacanth, veegum, and acacia. Sweeteners include sucrose, syrup, glycerin, and artificial sweeteners such as saccharin. Humectants include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate, and polyoxyethylene lauryl ether. Organic acids include citric acid and tartaric acid. Carbon dioxide sources include sodium bicarbonate and sodium carbonate. Colorants include any of the approved water-soluble FD and C dyes or mixtures thereof. Flavorings include natural flavorings extracted from plants such as fruits and synthetic blends of compounds that provide a pleasant taste.

[0291] For solid dosage forms, for example, a solution or suspension in propylene carbonate, vegetable oil, or triglycerides may, in one embodiment, be encapsulated in a gelatin capsule. Such solutions and formulations and their encapsulation are disclosed in U.S. Patents 4,328,245; 4,409,239; and 4,410,545. For liquid dosage forms, for example, a solution in polyethylene glycol may be diluted with a sufficient amount of a liquid medium, such as water, to facilitate measurement for administration.

[0292] Alternatively, liquid or semi-solid oral formulations may be prepared by dissolving or dispersing the active compound or salt in vegetable oil, glycol, triglycerides, propylene glycol esters (e.g., propylene carbonate), and other such carriers, and encapsulating the solution or suspension thereof in a hard or soft gelatin capsule shell. Other useful formulations include those shown in U.S. Patents RE28,819 and 4,358,603. In short, such formulations include, but are not limited to, the compounds provided herein, 1,2-dimethoxyethane, diglyme, triglyceride, tetraglyceride, polyethylene glycol-350-dimethyl ether, polyethylene glycol-550-dimethyl ether, polyethylene glycol-750-dimethyl ether (where 350, 550, and 750 are the approximate average molecular weights of polyethylene glycol), dialkylated mono or polyalkylene glycols, and one or more antioxidants such as butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl gallate, vitamins, hydroquinone, hydroxycoumarin, ethanolamine, lecithin, cephalin, ascorbic acid, malic acid, sorbitol, phosphoric acid, thiodipropionic acid and its esters, and dithiocarbamates.

[0293] Other formulations include, but are not limited to, aqueous alcohol solutions containing acetals. The alcohols used in these formulations are any water-miscible solvent having one or more hydroxyl groups, including propylene glycol and ethanol. The acetals include, but are not limited to, di(lower alkyl) acetals of lower alkylaldehydes, such as acetaldehyde diethyl acetal.

[0294] Non-enteral administration, characterized by subcutaneous, intramuscular, or intravenous injection in certain embodiments, is also intended here. The injectable preparation may be prepared in conventional forms, liquid solutions or suspensions, or solid forms or emulsions suitable for dissolving or suspending in liquid before injection. The injectable preparations, solutions, and emulsions may also contain one or more additives. Suitable additives include, for example, water, saline, dextrose, glycerol, or ethanol. Furthermore, if desired, the administered composition may also contain trace amounts of non-toxic auxiliary substances such as wetting or emulsifying agents, pH buffers, stabilizers, dissolution accelerators, and other such agents, such as sodium acetate, sorbitan monolaurate, triethanolamine oleate, and cyclodextrin.

[0295] The implants described here also include sustained-release or continuous-release systems that maintain a certain level of dosage (see, for example, U.S. Patent 3,710,795). In short, the compounds provided herein are insoluble in bodily fluids, solid internal matrices, hydrophilic polymers such as polymethyl methacrylic acid, polybutyl methacrylic acid, plasticized or unplasticized polyvinyl chloride, plasticized nylon, plasticized polyethylene terephthalic acid, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, ethylene-vinyl acetate copolymer, silicone rubber, polydimethylsiloxane, silicone carbonate copolymer, hydrogels of acrylic and methacrylic acid esters, collagen, crosslinked polyvinyl alcohol and crosslinked partially hydrolyzed polyvinyl acetate surrounded by an external polymer membrane, such as polyethylene, polypropylene, ethylene / propylene copolymer, ethylene / ethyl acrylic acid copolymer, ethylene / vinyl acetate copolymer, silicone rubber, polydimethylsiloxane, neoprene rubber, chlorinated polyethylene, polyvinyl chloride, vinyl chloride copolymer with vinyl acetate, vinylidene chloride, ethylene and propylene, ionomer polyethylene terephthalic acid, and butyl rubber. The compounds are dispersed in epichlorohydrin rubber, ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate / vinyl alcohol terpolymer, and ethylene / vinyl oxyethanol copolymer. The compounds diffuse through the polymer membrane during a release rate control step. The percentage of active compounds included in such non-enteral compositions depends highly on their specific properties as well as the compound's activity and the needs of the target.

[0296] Non-enteral administration of the composition includes intravenous, subcutaneous, and intramuscular administration. Formulations for non-enteral administration include sterile solutions for injection, sterile dried soluble products such as lyophilized powders ready to be combined with a solvent immediately before use, sterile suspensions ready for injection, sterile dried insoluble products ready to be combined with a medium immediately before use, and sterile emulsions. The solutions may be aqueous or non-aqueous.

[0297] If administered intravenously, a suitable carrier should include a solution containing physiological saline or phosphate-buffered saline (PBS) and a concentrating and solubilizing agent such as glucose, polyethylene glycol, polypropylene glycol, or mixtures thereof.

[0298] The media used in non-enteral preparations include aqueous media, non-aqueous media, antimicrobial agents, isotonic agents, buffers, antioxidants, local anesthetics, suspensions and dispersants, emulsifiers, chelating agents or sequestering agents, and other substances.

[0299] Examples of aqueous media include sodium chloride injection, Ringer's injection, isotonic dextrose injection, sterile water injection, and dextrose and lactated Ringer's injection. Non-aqueous non-enteral media include plant-derived fixed oils, cottonseed oil, corn oil, sesame oil, and peanut oil. Antimicrobial agents at bacteriostatic or fungal concentrations must be added to non-enteral preparations packaged in multi-dose containers and include phenol or cresol, mercury preparations, benzyl alcohol, chlorobutanol, methyl and propyl p-hydroxybenzoates, thimerosal, benzalkonium chloride, and benzethonium chloride. Isotonic agents include sodium chloride and dextrose. Buffers include phosphoric acid and citrate. Antioxidants include sodium bisulfate. Local anesthetics include procaine hydrochloride. Suspensions and dispersants include sodium carboxymethylcellulose, hydroxypropyl methylcellulose, and polyvinylpyrrolidone. Emulsifiers include polysorbate 80 (Tween (登録商標) 80) is included. The metal ion sequestering or chelating agent is EDTA. The carrier also includes ethyl alcohol, polyethylene glycol, and propylene glycol for water miscible media; and sodium hydroxide, hydrochloric acid, citric acid, or lactic acid for pH adjustment.

[0300] The compound concentration is adjusted so that the injection provides an effective dose to produce the desired pharmacological effect. The exact dose depends on the patient's or animal's age, weight, body surface area, and condition, as is known in this art.

[0301] The unit dose of the non-enteral preparation is packaged in ampoules, vials, or syringes with needles. All preparations for non-enteral administration must be sterile, as is known and practiced in this art.

[0302] As an example, intravenous or intra-arterial infusion of a sterile aqueous solution containing the active compound is an effective method of administration. Other embodiments include sterile aqueous or oily solutions or suspensions containing the active substance, which are injected as needed to produce the desired pharmacological effect.

[0303] The injectable formulation is designed for local and systemic administration. In one embodiment, the therapeutically effective dose is formulated to contain a concentration of the active compound greater than 0.1% w / w in the treated tissue, ranging from at least about 0.01% w / w to about 90% w / w or more. In one embodiment, the active compound is contained in the treated tissue at a concentration greater than 0.1% w / w.

[0304] The compound can be suspended in micronized or other suitable forms, or derivatized to produce a more soluble active product or prodrug. The form of the resulting mixture depends on several factors, including the intended method of administration and the solubility of the compound in the chosen carrier or medium. The effective concentration, sufficient to improve the symptoms of the condition, can be determined empirically.

[0305] The active ingredients provided herein may be administered by controlled release means or delivery devices well known to those skilled in the art. Examples include U.S. Patents 3,845,770;3,916,899;3,536,809;3,598,123;4,008,719;5,674,533;5,059,595;5,591,767;5,120,548;5,073,543;5,639,476;5,354,556;5,639,480;5,733,566;5,739,108;5,891,474;5,922,356;5,9 This includes, but is not limited to, those described in 72,891; 5,980,945; 5,993,855; 6,045,830; 6,087,324; 6,113,943; 6,197,350; 6,248,363; 6,264,970; 6,267,981; 6,376,461; 6,419,961; 6,589,548; 6,613,358; 6,699,500 and 6,740,634. Such dosage forms can be used to provide sustained or controlled release of one or more active ingredients, for example, by using hydroxypropyl methylcellulose, other polymer matrices, gels, permeable membranes, permeation systems, multilayer coatings, microparticles, liposomes, microspheres, or combinations thereof in various ratios to provide desired release profiles. Suitable controlled-release formulations known to those skilled in the art, including those described herein, can be readily selected for use with the active ingredient provided herein.

[0306] All controlled-release products share the common objective of improving drug therapy beyond what can be achieved with uncontrolled counterparts. Ideally, the use of optimally designed controlled-release formulations in medical procedures is characterized by controlling the state with the minimum amount of drug substance used in the treatment or in the shortest possible time. The advantages of controlled-release formulations include long-term drug activity, reduced dose frequency, and increased patient compliance. Furthermore, controlled-release formulations can be used to influence the onset time of action or other characteristics such as drug blood levels, and therefore, the onset of side effects (e.g., adverse effects).

[0307] Most controlled-release formulations are designed to release an initial amount of the drug (active ingredient) that rapidly produces the desired therapeutic effect, and then gradually and continuously release other amounts of the drug to maintain a long-term therapeutic or prophylactic level. To maintain a constant level of this drug in the body, the drug must be released from the dosage form at a rate that replaces the amount of drug metabolized and excreted from the body. The controlled release of the active ingredient can be stimulated by a variety of conditions, including but not limited to pH, temperature, enzymes, water, or other physiological conditions or compounds.

[0308] In one embodiment, the drug may be administered using intravenous infusion, an implantable osmotic pump, a transdermal patch, liposomes, or other administration methods. In one embodiment, a pump may be used (see Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989)). In another embodiment, polymeric materials may be used. In another embodiment, the controlled-release system may be positioned proximal to the therapeutic target, i.e., requiring only a portion of the systemic dose (see, for example, Goodson, Medical Applications of Controlled Release, vol. 2, pp. 115138 (1984)). In one embodiment, the controlled-release device is introduced target proximal to inappropriate immune activation or tumor site. Other controlled emission systems are described in Langer's debut (Science 249:1527-1533 (1990)).The active ingredients are contained within a solid internal matrix insoluble in bodily fluids, such as hydrophilic polymers like polymethyl methacrylic acid, polybutyl methacrylic acid, plasticized or unplasticized polyvinyl chloride, plasticized nylon, plasticized polyethylene terephthalic acid, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, ethylene-vinyl acetate copolymer, silicone rubber, polydimethylsiloxane, silicone carbonate copolymer, hydrogels of acrylic and methacrylic acid esters, collagen, crosslinked polyvinyl alcohol and crosslinked partially hydrolyzed polyvinyl acetate surrounded by an outer polymer film, such as polyethylene, polypropylene, ethylene / propylene copolymer, ethylene / ethyl acrylic acid copolymer, ethylene / vinyl acetate copolymer, silicone rubber, polydimethylsiloxane, neoprene rubber, chlorinated polyethylene, polyvinyl chloride, vinyl chloride copolymer with vinyl acetate, vinylidene chloride, ethylene and propylene, ionomer polyethylene terephthalic acid, and butyl rubber. The active ingredient can be dispersed in epichlorohydrin rubber, ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate / vinyl alcohol terpolymer, and ethylene / vinyl oxyethanol copolymer. The active ingredient is then diffused through the polymer membrane in a release rate control step. The percentage of the active ingredient contained in such a non-enteral composition depends highly on its specific properties and the needs of the target.

[0309] What is interesting here is that it is also a lyophilized powder that can be reconstituted for administration as a solution, emulsion, and other mixture. It can also be reconstituted and formulated as a solid or gel.

[0310] Sterile, lyophilized powders are prepared by dissolving the compound or its derivatives provided herein in a suitable solvent. The solvent may contain additives that improve stability or other pharmacological components of the powder or reconstituted solution prepared from the powder. Possible additives include, but are not limited to, antioxidants, buffers, and fillers. In one embodiment, the additive is selected from dextrose, sorbitol, fructose, corn syrup, xylitol, glycerin, glucose, sucrose, and other suitable additives. The solvent is a buffer such as citrate, sodium phosphate, or potassium phosphate, or other such buffers, at approximately neutral pH. The desired formulation is obtained by sterile filtration of the solution under standard conditions known to those skilled in the art, followed by lyophilization. In one embodiment, the obtained solution is dispensed into lyophilized vials. Each vial contains a single dose or multiple doses of the compound. The lyophilized powder can be stored under suitable conditions, such as about 4°C to room temperature.

[0311] Reconstitution of this lyophilized powder with sterile water for injection yields a formulation for non-enteral administration. For reconstitution, the lyophilized powder is added to sterile water or another suitable carrier. The exact amount depends on the selected compound. Such amounts can be determined empirically.

[0312] The topical mixture is prepared as described for topical and systemic administration. The resulting mixture may be a solution, suspension, emulsion, etc., and may be formulated into a cream, gel, ointment, emulsion, solution, elixir, lotion, suspension, tincture, paste, foam, aerosol, irrigation, spray, suppository, bandage, skin patch, or any other formulation suitable for topical administration.

[0313] The compound or its derivatives can be formulated into aerosols for topical application, such as by inhalation (see, for example, U.S. Patents 4,044,126, 4,414,209 and 4,364,923 describing aerosols for the delivery of steroids useful in the treatment of inflammatory diseases, particularly asthma). These formulations for administration into the respiratory tract may be in the form of aerosols for nebulizers or solutions or fine powders for blowing, either alone or in combination with an inert carrier such as lactose. In such cases, the formulation particles have a mass median geometric diameter of less than 5 microns in one embodiment and less than 10 microns in other embodiments.

[0314] Oral inhalation formulations of compounds or derivatives suitable for inhalation include metered-dose inhalers, dry powder inhalers, and liquid formulations administered from nebulizers or metered-dose liquid dispensing systems. For both metered-dose inhalers and dry powder inhalers, the crystalline form of the compound or derivative is the preferred physical form of the drug to provide long-term product stability.

[0315] In addition to particle size reduction methods known to those skilled in the art, crystalline particles of compounds or derivatives can be produced using supercritical fluid processing, which offers significant advantages in the production of such particles for inhalation delivery by producing respiratory particles of a desired size in a single step (e.g., International Publication WO2005 / 025506). The controlled particle size of the microcrystals can be selected to ensure that a substantial proportion of the compound or derivative is deposited in the lungs. In one embodiment, these particles have a mass-central aerodynamic diameter of about 0.1 to about 10 microns, in another embodiment, about 1 to about 5 microns, and in yet another embodiment, about 1.2 to about 3 microns.

[0316] Inert and non-flammable HFA propellants are selected from HFA134a (1,1,1,2-tetrafluoroethane) and HFA227e (1,1,1,2,3,3,3-heptafluoropropane) and are provided individually or in ratios suitable for crystalline particles of compounds or derivatives. The ratios are also selected to ensure that the product suspension avoids harmful precipitation or cream (which may be irreversible aggregation precipitation) and instead promotes a loose aggregation system that disperses easily upon shaking. A loose aggregation system is well considered to provide optimal stability in pMDI canisters. As a result of the nature of the formulation, the formulation is free of ethanol and surfactants / stabilizers.

[0317] The compound may be formulated in the form of gels, creams, and lotions for topical or local application to mucous membranes such as the skin and eyes, and for application to the eyes or for intracapsular or intrathecal application. Topical administration is intended for transdermal delivery, as well as for administration to the eyes or mucous membranes or for inhalation therapy. Nasal solutions of the active compound alone or in combination with other additives may also be administered.

[0318] For nasal administration, the formulation contains an esterified phosphonic acid compound dissolved or suspended in a liquid carrier, particularly an aqueous carrier, for aerosol application. The carrier may contain solubilizing or suspending agents such as propylene glycol, surfactants, absorption enhancers such as lecithin or cyclodextrin, or preservatives. Solution formulations, especially those intended for ophthalmic use, can be prepared as 0.01% to 10% isotonic solutions with a pH of approximately 5 to 7.4 using appropriate salts.

[0319] Transdermal patches containing iontophoretic and electrophoretic devices, as well as other routes of administration such as rectal administration, are also intended herein. Transdermal patches containing iontophoretic and electrophoretic devices are well known to those skilled in the art. For example, such patches are disclosed in U.S. Patents 6,267,983, 6,261,595, 6,256,533, 6,167,301, 6,024,975, 6,010715, 5,985,317, 5,983,134, 5,948,433 and 5,860,957.

[0320] For example, dosage forms for rectal administration include rectal suppositories, capsules, and tablets for systemic effects. Rectal suppositories are used here to mean solid objects inserted into the rectum that melt or soften at body temperature to release one or more pharmacological or therapeutic active ingredients. Substances used in rectal suppositories are bases or media and agents that raise the melting point. Examples of bases include cocoa butter (theobroma oil), glycerin-gelatin, carbowax (polyoxyethylene glycol), and suitable mixtures of mono, di, and triglycerides of fatty acids. Various combinations of bases can be used. Agents that raise the melting point of suppositories include whale wax and other waxes. Rectal suppositories can be manufactured by compression or casting. The weight of a rectal suppository is, in some embodiments, about 2-3 gm. Tablets and capsules for rectal administration use the same substances and are manufactured in the same manner as formulations for oral administration.

[0321] The compounds or derivatives provided herein may also be formulated to target specific tissues, receptors, or other areas of the body being treated. Many such targeting methods are well known to those skilled in the art. All such targeting methods are intended herein for use in the present composition. For non-limiting examples of targeting methods, see, for example, U.S. Patents 6,316,652, 6,274,552, 6,271,359, 6,253,872, 6,139,865, 6,131,570, 6,120,751, 6,071,495, 6,060,082, 6,048,736, 6,039,975, 6,004,534, 5,985,307, 5,972,366, 5,900,252, 5,840,674, 5,759,542 and 5,709,874.

[0322] In one embodiment, liposome suspensions containing tissue-targeted liposomes, such as tumor-targeted liposomes, may also be suitable as carriers. These can be prepared by methods known to those skilled in the art. For example, liposome formulations can be prepared as described in U.S. Patent 4,522,811. Briefly, liposomes such as multilayer vesicles (MLVs) can be formed by drying phosphatidylcholine and phosphatidylserine (7:3 molar ratio) inside a flask. A solution of the compound provided herein in phosphate-buffered saline (PBS) free of divalent cations is added, and the flask is shaken until the lipid film is dispersed. The resulting vesicles are washed to remove any unencapsulated compounds, pelletized by centrifugation, and then resuspended in PBS.

[0323] The compound or its derivative is packaged in packaging material, and the packaging material contains a label indicating that the compound or its derivative provided herein is effective in treating, preventing, or improving one or more symptoms of the above-mentioned disease or disorder, and that the compound or composition or its derivative is used in treating, preventing, or improving one or more symptoms of the above-mentioned disease or disorder.

[0324] The products provided herein include packaging materials. Packaging materials used for packaging the products are well known to those skilled in the art. See, for example, U.S. Patents 5,323,907, 5,052,558 and 5,033,252. Examples of packaging materials include, but are not limited to, blister packs, bottles, tubes, inhalers, pumps, bags, vials, containers, syringes, bottles and any packaging suitable for the selected formulation and the intended method of administration and treatment. A wide range of formulations of the compounds and compositions provided herein are intended as well as for the diverse treatment of any of the diseases or disorders described herein.

[0325] Dosage For use in the treatment or prevention of disease, the compounds or pharmaceutical compositions described herein are administered or applied in therapeutically effective doses. In human treatment, the physician determines the most appropriate dosage regimen for prophylactic or curative treatment, taking into account age, weight, disease stage, and other factors specific to the subject being treated. The amount of active ingredient in the formulations provided herein that are effective in the prevention or treatment of infectious diseases varies with the nature and severity of the disease or condition and the route through which the active ingredient is administered. The frequency and dose also vary depending on the specific treatment being administered (e.g., therapeutic or prophylactic agent), the severity of the infection, the route of administration, and factors specific to each subject, as well as the subject's age, body, weight, response, and medical history.

[0326] Examples of formulation dosages include milligrams or micrograms of the active compound per kilogram of the substance (e.g., approximately 1 microgram / kilogram to approximately 50 milligrams / kilogram, approximately 10 micrograms / kilogram to approximately 30 milligrams / kilogram, approximately 100 micrograms / kilogram to approximately 10 milligrams / kilogram, or approximately 100 micrograms / kilogram to approximately 5 milligrams / kilogram).

[0327] In one embodiment, the therapeutically effective dose must produce a serum concentration of the active ingredient of about 0.001 ng / ml to about 50 to 200 μg / ml. In other embodiments, the composition must provide a dosage of about 0.0001 mg to about 70 mg of the compound per kilogram of body weight per day. The unit dosage forms are prepared to provide a combination of the active ingredient or essential ingredient of about 0.01 mg, 0.1 mg or 1 mg per unit dosage form to about 500 mg, 1000 mg or 5000 mg, and in one embodiment, about 10 mg to about 500 mg.

[0328] The active ingredient may be administered as a single dose or in several small doses at time intervals. It is understood that the exact dosage and duration of treatment are functions of the disease being treated and may be determined empirically using known test protocols or by extrapolation of in vivo or in vitro test data or subsequent clinical trials. It should be noted that concentrations and dosage values ​​may also vary depending on the severity of the condition to be alleviated. For any particular subject, a specific dosage regimen should be adjusted over time according to individual needs and the professional judgment of the person administering or supervising the administration of the composition, and it should be further understood that the concentration ranges shown herein are merely examples and are not intended to limit the scope or implementation of the composition.

[0329] As will be apparent to those skilled in the art, in some cases it may be necessary to use dosages of the active ingredient outside the scope disclosed herein. Furthermore, clinicians or treating physicians know how and when to interrupt, adjust, or discontinue treatment in relation to the subject's response.

[0330] For systemic administration, the therapeutically effective dose can initially be estimated from in vitro assays. For example, the dose can be determined by an IC in cell culture. 50 (i.e., a lethal concentration of the test compound in 50% of the cell cultures) or IC determined in the cell culture 100 Animal models can be formulated to achieve a circulating concentration range that includes (i.e., a concentration of the lethal compound in 100% of the cell culture). Using such information, useful doses in humans can be determined more accurately.

[0331] The initial dose can also be estimated from in vivo data (e.g., animal models) using techniques well known in the art. Those skilled in the art can easily optimize the dose to humans based on the animal data.

[0332] Alternatively, the initial dose can be used to determine the IC of a specific compound disclosed herein and a known compound. 50 MIC and / or I 100 By comparing these values ​​and adjusting the initial dose accordingly, the optimal dose can be determined from the doses administered for known drugs. The optimal dose can be obtained from these initial values ​​through optimization of conventional practices.

[0333] In the case of local administration or selective uptake, the effective local concentration of the compound used may not correlate with the plasma concentration. Those skilled in the art can optimize the therapeutically effective local dose without excessive experimentation.

[0334] Ideally, the therapeutically effective doses of the compounds described herein should provide therapeutic benefits without causing substantial toxicity. The toxicity of the compounds should be assessed using standardized LD50 in cell cultures or experimental animals, for example. 50 (A lethal dose in 50% of the population) or LD 100 This can be determined by determining the dose that is lethal to 100% of the population. The dose-to-toxicity ratio is the therapeutic index. Compounds exhibiting a high therapeutic index are preferred. Data obtained from these cell culture assays and animal studies can be used to formulate a non-toxic dose range for use in the target population. The doses of the compounds described herein are preferably within the range of circulating concentrations that include effective doses with little to no toxicity. Doses may vary within this range depending on the dosage form used and the route of administration utilized. The exact formulation, route of administration, and dose may be selected by individual physicians in light of the patient's condition (e.g., Fingl et al., 1975, in The Pharmacological Basis of Therapeutics, Ch.1, p.1).

[0335] Treatment may be repeated intermittently. In one embodiment, administration of the same formulation provided herein may be repeated, with intervals of at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months between administrations.

[0336] Combination therapy The compounds of formula (I) and their pharmaceutical compositions disclosed herein may also be used in combination with one or more other active ingredients. In some embodiments, the compounds of formula (I) and their pharmaceutical compositions may be administered in combination with or sequentially with other therapeutic agents. Such other therapeutic agents include those known to treat, prevent or improve one or more conditions associated with idiopathic pulmonary fibrosis, interstitial lung disease, systemic lupus erythematosus-associated interstitial lung disease, rheumatoid arthritis, diabetic nephropathy, focal segmental glomerulosclerosis, chronic kidney disease, non-alcoholic fatty liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, solid tumors, hematological malignancies, organ transplantation, Alport syndrome, interstitial lung disease, radiation-induced fibrosis, bleomycin-induced fibrosis, asbestos-induced fibrosis, influenza-induced fibrosis, coagulation-induced fibrosis, vascular injury-induced fibrosis, aortic stenosis, and cardiac fibrosis.

[0337] Examples of compounds of formula (I) and their pharmaceutical compositions and therapeutic agents that can be used include components and fragments of bee venom, pollen, milk, peanuts, CpG motifs, collagen, other components of the extracellular matrix, antihistamines (e.g., cetirizine, loratadine, acribastine, fexofenadine, chlorphenamine, etc.), corticosteroids (e.g., fluticasone propionate, fluticasone furoate, beclomethasone dipropionate, budesonide, cicle (e.g., Sonide, mometasone florat, triamcinolone, flunisolide, prednisolone, hydrocortisone), NSAIDs (e.g., aspirin, ibuprofen, naproxen), leukotriene modulators (e.g., montelukast, zafilkast, pranlukast), iNOS inhibitors, tryptase inhibitors, p38 inhibitors (e.g., rosmapimod, dilmapimod), elastase inhibitors, beta-2 agonists, DP1 antagonists, DP2 antagonists, pl 3K delta inhibitors, lysophosphatidic acid inhibitors or 5-lipoxygenase-activating protein inhibitors (e.g., sodium 3-(3-(tert-butylthio)-1-(4-(6-ethoxypyridine-3-yl)benzyl)-5-((5-methylpyridine-2-yl)methoxy)-1H-indole-2-yl)-2,2-dimethylpropanoate, etc.), adenosine agonists (e.g., adenosine, regadenoson, etc.), chemokine antagonists (e.g., CCR3 antagonists, CCR4 antagonists, etc.), mediator-release inhibitors, DMARDs (e.g., methotrexate, leflunomide, azathioprine, etc.), biopharmaceutical therapies (e.g., anti-IgE, anti-TNF, anti-interleukin (e.g., anti-IL-1, anti-IL-6, anti-IL-1) L-12, anti-IL-17, anti-IL-18, etc.), receptor therapies (e.g., etanercept), interferons, cytokines, chemokines, cytokine and chemokine receptor modulators, cytokine agonists or antagonists, TLR agonists, TGF synthesis inhibitors (e.g., pirfenidone), tyrosine kinase inhibitors that target vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) This includes, but is not limited to, fibroblast growth factor (FGF) receptor kinases, imatinib mesylate (i.e., Gleevec), endothelin receptor antagonists (e.g., ambrisentan or macitentan), antioxidants (e.g., N-acetylcysteine ​​(NAC)), broad-spectrum antibiotics (e.g., cotrimoxazole, tetracycline, etc.), phosphodiesterase 5 inhibitors (e.g., sildenafil), anti-ανβχ antibodies and anti-ανββ monoclonal antibodies, bronchodilators (e.g., salbutamol), long-acting 2-agonists (e.g., salmeterol, formoterol, vilanterol, etc.), sh...

Claims

1. Equation (Ia) 【Chemistry 1】 {During the ceremony, q is either 1 or 2; R ３ Independently, halogen and C in each case １－４ Alkyl and -C(O)N(R) １１ ) ２ Selected from; o is 0, 1, or 2; D is selected from bond and -C(O)-; E is C １－４ It is alkylene; X-Y is λ -C(O)N(R １４ )-, λ -N(R １４ )C(O)-, λ -N(R １４ )C(O)CH ２ - λ -N(R １４ )CH ２ - λ -CH ２ N(R １４ )- λ -O- λ -OCH ２ -and λ -CH ２ O-; selected from Here, R １４ In each case, hydrogen and C １－４ Selected from alkyl groups; λ It is from X-Y 【Chemistry 2】 It means a connection to; R ６ and R ７ Each of these is independently hydrogen, halogen, and C in each case. １－４ Alkyl, C １－４ Haloalkyl, -OR １６ and selected from -CN; A is (i) and (ii): (i) Hydrogen, halogens and -CN; (ii) C ３－１２ Carbon rings and 3- to 12-membered heterorings (in both cases: Halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -N(R １７ )C(O)R １７ , -N(R １７ )S(O) ２ (R １７ ), =O, =S and -CN; Depending on the case, halogen, - OR １７ , -N(R １７ ) ２ , -N(R １７ )C(O)R １７ , -N(R １７ )S(O) ２ (R １７ ), -S(OR) １７ C is substituted with one or more substituents independently selected from ,=O and -CN. １－６ alkyl; and In all cases, halogen or C １－４ Alkyl, C １－４ C is substituted with one or more substituents independently selected from haloalkyl and =O. ３－１０ Carbon rings and 3- to 10-membered heterorings (Substituted with one or more substituents independently selected from) Selected from; When A is selected from (ii), B is selected from (I) or When A is selected from (i), B is selected from (II): (I) Hydrogen, halogens and -CN; (II) - N(R １８ ) ２ , -N(R １８ )C(O)R １８ , -N(R １８ )C(O)OR １８ , -N(R １８ )C(O)N(R １８ ) ２ and -N(R １８ )S(O) ２ (R １８ ); and C ３－１２ Carbon rings and 3- to 12-membered heterorings [both depending on the case: Halogen, -OR １８ , -N(R １８ ) ２ , -C(O)R １８ , = O and -CN; C １－６ Alkyl (depending on the case: Halogen, -OR １８ , -SR １８ , -N(R １８ ) ２ , -C(O)R １８ , = O, -CN, C ３－６ Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from, Here, C ３－６ The carbon rings and 3- to 6-membered heterorings may each contain halogens, C １－４ Alkyl, C １－４ (substituted with one or more substituents independently selected from haloalkyl and =O); and C 3-10 carbon rings and 3-10 membered heterorings (both depending on the case): Halogens, C1-4 alkyls, C1-4 haloalkyls and =O (Substituted with one or more substituents independently selected from the original); R11 and R １６ Each of them is independently hydrogen, C in each case. １－４ Alkyl and C １－４ Selected from haloalkyls; R １７ Each case is independent: hydrogen; In some cases, halogen, -OR ２１ , -SR ２１ , -N(R ２１ ) ２ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ) ２ , -C(O)N(R ２１)２ ]>, -N(R ２１ )C(O)R ２１ , -NO ２ , =O, =S, =N(R ２１ ), -N ３ And substituted with one or more substituents independently selected from -CN is C １－６ Alkyl; and In all cases, halogen or C １－４ Alkyl, C １－４ Haloalkyl, -OR ２１ , -SR ２１ , -N(R ２１ ) ２ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ) ２ , -C(O)N(R ２１ ) ２ , -N(R ２１ )C(O)R ２１ , -N(R ２１ )C(O)OR ２１ , -N(R ２１ )C(O)N(R ２１ ) ２ , -N(R ２１ )C(S)N(R ２１ ) ２ , -N(R ２１ )S(O) ２ (R ２１ ), -S(OR) ２１ , -S(O) ２ R ２１ , -S(O) ２ N(R) ２１ ) ２ , -NO ２ , =O, =S, =N(R ２１ ), -N ３ and C substituted with one or more substituents independently selected from -CN ３－６ Carbon rings and 3- to 6-membered heterorings Selected from; R １８ Each case is independent: hydrogen; C １－６ Alkyl (depending on the case: Halogen, -OR ２２ , -SR ２２ , -N(R ２２ ) ２ , -C(O)R ２２ , -C(O)OR ２２ , -OC(O)R ２２ , -OC(O)N(R ２２ ) ２ , -C(O)N(R ２２ ) ２ , -N(R ２２ )C(O)R ２２ , -NO ２ , =O, =S, =N(R ２２ ), -N ３ ,-CN,C ３－１０ Carbon rings and 3- to 10-membered heterorings It is substituted with one or more substituents independently selected from, Here, C ３－１０ The carbon rings and 3- to 10-membered heterorings may each contain halogens, C １－６ Alkyl, C １－６ Haloalkyl, -OR ２２ , -SR ２２ and -N(R ２２ ) ２ (substituted with one or more substituents independently selected from; and C ３－１０ Carbon rings and 3- to 10-membered heterorings (in both cases: Halogen, C １－６ Alkyl, C １－６ Haloalkyl, -OR ２２ , -SR ２２ , -N(R ２２ ) ２ , -C(O)R ２２ , -C(O)OR ２２ , -OC(O)R ２２ , -OC(O)N(R ２２ ) ２ , -C(O)N(R ２２ ) ２ , -N(R ２２ )C(O)R ２２ , -N(R ２２ )C(O)OR ２２ , -N(R ２２ )C(O)N(R ２２ ) ２ , -N(R ２２ )C(S)N(R ２２ ) ２ , -N(R ２２ )S(O) ２ (R ２２ ), -S(OR) ２２ , -S(O) ２ R ２２ , -S(O) ２ N(R) ２２ ) ２ , -NO ２ , =O, =S, =N(R ２２ ), -N ３ ,-CN,C ３－６ Carbon rings and 3- to 6-membered heterorings It is substituted with one or more substituents independently selected from; Here, C ３－６ The carbon rings and 3- to 6-membered heterorings may each contain halogens, C １－４ Alkyl and C １－４ (Substituted with one or more substituents independently selected from the haloalkyl group.) Selected from; R ２１ and R ２２ Each of these is independent in each case: hydrogen; Depending on the case, halogens, hydroxyls, C ３－６ C is substituted with one or more substituents independently selected from carbon rings and 3- to 6-membered heterorings. １－４ Alkyl (where each C ３－６ Carbon rings and 3- to 6-membered heterorings are sometimes C １－４ Alkyl, -N(R ２３ ) ２ and -C(O)N(R ２３ ) ２ (substituted with one or more substituents independently selected from; and C ３－６ Carbon rings and 3- to 12-membered heterorings (both may contain halogens, C) １－４ Alkyl, C １－４ Haloalkyl, C １－４ (Substituted with one or more substituents independently selected from alkoxy and =O) Selected from; and R ２３ Independently, hydrogen and C in each case １－４ Selected from alkyl groups. Compounds of or pharmaceutically acceptable salts thereof.

2. The compound or salt of claim 1, wherein q is 1 or 2.

3. X-Y λ -C(O)N(R) １４ )-、 λ -N(R １４ )C(O)- and λ - OCH ２ - is selected from; and R １４ The compound or salt of claim 1, wherein the compound is hydrogen.

4. R １１ , R １４ , and R １６ The compound or salt of claim 1, wherein each of the elements is selected from hydrogen in each case.

5. R ６ R is selected from hydrogen and -OH; and R ７ The compound or salt of claim 1, wherein is selected from hydrogen and halogens.

6. R ６ and R ７ The compound or salt of claim 1, wherein each of the atoms is selected from hydrogen.

7. The compound or salt of claim 1, wherein A is selected from hydrogen, halogens, and -CN.

8. The compound or salt of claim 7, wherein A is hydrogen.

9. The compound or salt of claim 1, wherein B is selected from hydrogen, halogens, and -CN.

10. The compound or salt of claim 9, wherein B is selected from hydrogen and halogens.

11. A is C ３－１２ A compound or salt of claim 1, selected from a carbocyclic ring and a 3- to 12-membered heterocycle, each optionally substituted with one or more substituents.

12. A's C ３－１２ The compound or salt of claim 11, wherein the carbocyclic and 3- to 12-membered heterocycle are selected from phenyl; pyridine; indan; chroman; benzodioxole; 2,3-dihydrobenzofuran; quinoline; 1,2,3,4-tetrahydronaphthalene; naphthalene; quinoxaline; 2',3'-dihydrospiro[cyclopropane-1,1'-indene]; and pyrazole; each is optionally substituted with one or more substituents.

13. If A has one or more substituents, then the substituents present are halogens, -OR １７ , C １－６ Alkyl, C １－６ Haloalkyl, C ３－１０ Carbon rings and 3- to 10-membered heterorings (where C ３－１０ A carbon ring and a 3- to 10-membered heteroring are each optionally C １－４ Alkyl, C １－４ A compound or salt of claim 12, selected from (substituted with one or more substituents independently selected from haloalkyl and =O).

14. R １７ Independently, hydrogen and C in each case １－６ Alkyl, C ３－６ A compound or salt of claim 1, selected from a carbocyclic ring and a 3- to 6-membered heterocycle.

15. If A has one or more substituents, then the substituents present are halogen, hydroxyl, methoxy, trifluoromethyl, propyl, cyclopropyl, cyclopentyl, phenyl, phenoxy, 【Transformation 3】 A compound or salt of claim 1, selected from the above.

16. A 【Chemistry 4】 【Transformation 5】 A compound or salt of claim 1, selected from the above.

17. R １８ Independently, hydrogen and C in each case １－６ Alkyl, C ３－１０ Selected from carbocyclic and 3- to 10-membered heterocycles, where C １－６ Alkyl, C ３－１０ The compound or salt of claim 1, wherein the carbon ring and the 3- to 10-membered heteroring are each optionally substituted with one or more substituents.

18. R １８ C ３－１０ The compound or salt of claim 17, wherein the carbocyclic ring and the 3- to 10-membered heterocycle are independently selected in each case from pyrrolidine, piperidine, phenyl, indoline, bicyclo[2.2.2]octane, cyclohexane, tetrahydropyran, pyridine, oxadiazole, pyrimidine, quinazoline, naphthalene, quinoline, thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, benzothiazole, indan, thieno[2,3-d]pyrimidine oxide, and cyclopropyl, each of which is optionally substituted with one or more substituents.

19. R １８ C ３－１０ The carbon ring and the 3- to 10-membered heteroring each independently form a halogen, C １－６ Alkyl, C １－６ Haloalkyl, -OR ２２ , -N(R ２２ ) ２ , -C(O)R ２２ , -C(O)N(R ２２ ) ２ , -N(R ２２ )C(O)R ２２ , -S(O) ２ R ２２ , = O, -CN, C ３－６ Carbon rings and 3- to 6-membered heterorings, where C ３－６ The carbon ring and the 3- to 6-membered heteroring may each be a halogen, C １－４ Alkyl and C １－４ The compound or salt of claim 17, which is substituted with one or more substituents independently selected from the haloalkyl group, and is optionally substituted with one or more substituents selected from the haloalkyl group.

20. R １８ C ３－１０ The carbon ring and the 3- to 10-membered heteroring each independently form a halogen, C １－６ Alkyl, C １－６ Haloalkyl, -N(R) ２２ ) ２ , -C(O)R ２２ , -C(O)N(R ２２ ) ２ , -S(O) ２ R ２２ , = O, C ３－６ Carbon rings and 3- to 6-membered heterorings, where C ３－６ The carbon ring and the 3- to 6-membered heteroring are optionally halogens and C １－４ The compound or salt of claim 19, which is substituted with one or more substituents independently selected from the haloalkyl group, and is optionally substituted with one or more substituents independently selected from the haloalkyl group.

21. R ２２ Independently, hydrogen and C in each case １－４ Alkyl, C ３－６ Selected from carbon rings and 3- to 6-membered heterorings, where C ３－６ The carbon ring and the 3- to 6-membered heteroring are each C １－４ Alkyl and C １－４ The compound or salt of claim 17, which is substituted with one or more substituents independently selected from the alkoxy.

22. R １８ C ３－１０ The carbocyclic ring and the 3- to 10-membered heterocycle are each independently of halogen, methyl, trifluoromethyl, cyclopropyl, phenyl, and -NH in each case. ２ , = O, 【Transformation 6】 The compound or salt of claim 17, optionally substituted with one or more substituents selected from the following.

23. B 【Transformation 7】 【Transformation 8】 A compound or salt of claim 1, selected from the above.

24. B's C ３－１２ The compound or salt of claim 1, wherein the carbocyclic ring and the 3- to 12-membered heterocycle are selected from phenyl; pyridinyl, naphthyl; 1,2,3,4-tetrahydronaphthalene; indan; 7-azaindole; indazole; and chroman, each of which is optionally substituted with one or more substituents.

25. B's C ３－１２ The carbon ring and the 3- to 12-membered heteroring are each in some cases Halogen and -OR １８ ; Depending on the case, halogen, OR １８ and C ３－６ A carbon ring substituted with one or more substituents independently selected from the carbon ring. １－６ alkyl; and C ３－１０ Carbon rings and 3- to 10-membered heterorings (where C ３－１０ The carbon ring and the 3- to 10-membered heteroring are optionally halogens and C １－４ (Substituted with one or more substituents independently selected from the alkyl group) The compound or salt of claim 24, which is substituted with one or more substituents independently selected from the compound.

26. B's C ３－１２ The carbocyclic ring and the 3- to 12-membered heterocycle may each be a halogen, trifluoromethyl, cyclopropyl, phenyl, 【Chemistry 9】 The compound or salt of claim 24, which is substituted with one or more substituents independently selected from the compound.

27. B 【Chemistry 10】 A compound or salt of claim 1, selected from the above.

28. The compound of formula (Ia) 【Chemistry 11】 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 [Chemistry 18] 【Chemistry 19】 【Chemistry 20】 【Chemistry 21】 【Chemistry 22】 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 【Chemistry 26】 【Chemistry 27】 【Chemistry 28】 【Chemistry 29】 【Transformation 30】 【Chemistry 31】 【Chemistry 32】 The compound or salt of claim 1, selected from a pharmaceutically acceptable salt thereof.

29. A pharmaceutical composition comprising a pharmaceutically acceptable additive and any compound or salt of any of claims 1 to 28.

30. An alpha-V integrin regulator comprising any compound or salt of claims 1 to 28.

31. The agent according to claim 30, wherein alpha-V integrin is alpha-V beta-1 integrin.

32. The agent according to claim 30, wherein alpha-V integrin is alpha-V beta-6 integrin.

33. A therapeutic agent comprising any compound or salt of claims 1 to 28 for the treatment of a disease or condition selected from idiopathic pulmonary fibrosis, systemic lupus erythematosus-associated interstitial lung disease, rheumatoid arthritis, diabetic nephropathy, focal segmental glomerulosclerosis, chronic kidney disease, non-alcoholic fatty liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, solid tumors, hematological malignancies, organ transplantation, Alport syndrome, interstitial lung disease, radiation-induced fibrosis, bleomycin-induced fibrosis, asbestos-induced fibrosis, influenza-induced fibrosis, coagulation-induced fibrosis, vascular injury-induced fibrosis, aortic stenosis, and cardiac fibrosis.

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