MTORC1 Modulators and Uses Thereof

Abstract

To provide compounds and salts exhibiting high selectivity and inhibitory activity against mTORC1, and to provide uses thereof for treating diseases.SOLUTION: In certain embodiments, the present disclosure provides a method of treating a disease, wherein the disease is selected from chronic diseases. The chronic diseases may be selected from diseases in which the mTORC1 is hyperactivated. The chronic diseases may be selected from diseases in which chronic diseases would benefit from inhibiting mTORC1. In certain embodiments, the chronic diseases may be selected from age-related diseases that result in overactivity of mTORC1, including neurodegenerative diseases, neurocutaneous diseases, neurodevelopmental disorders, mTORopathies, tauopathies, cognitive disorders, epilepsy, autism spectrum disorders, autoimmune diseases, metabolic diseases, cancer, autophagy disorders, infectious diseases, cardiovascular diseases, muscle atrophy, inflammatory diseases, kidney diseases, lung diseases, eye disorders, or decreased immune activity in the elderly.SELECTED DRAWING: None

Description

[Technical Field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application Nos. 63 / 001,187, filed March 27, 2020, 63 / 001,144, filed March 27, 2020, 63 / 001,177, filed March 27, 2020, 63 / 019,176, filed May 1, 2020, 63 / 054,763, filed July 21, 2020, 63 / 054,762, filed July 21, 2020, and 63 / 054,768, filed July 21, 2020, the entire contents of each of which are incorporated herein by reference. [Background technology]

[0002] Background of the Invention The potential therapeutic potential of rapamycin has been established for many chronic diseases, from Alzheimer's and Parkinson's diseases to diabetes and cardiovascular disease. However, its prohibitive safety profile for long-term treatment has limited its use for the treatment of various diseases. Rapamycin, an FDA-approved compound, inhibits mTOR signaling and extends the lifespan of some species, but can induce adverse effects such as peripheral edema, hypercholesterolemia, muscosal ulcers, abdominal pain, headache, nausea, diarrhea, pain, constipation, hypertriglyceridemia, hypertension, increased creatinine, fever, urinary tract infections, anemia, arthralgia, and thrombocytopenia. Given the complications associated with rapamycin, new agents are needed. Summary of the Invention [Means for solving the problem]

[0003] Summary of the Invention In a first aspect, the present disclosure provides a compound represented by the structure of Formula I: [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 is -OH, [ka] , 3- to 10-membered heterocycles, and C 3~10 carbocycle, and the 3- to 10-membered heterocycle and C 3~10 The carbocycles are each selected from the group consisting of hydroxy, halogen, -CN, -NO2, ═O, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 alkoxy, 3- to 10-membered heterocycles, and C 3~10 and a 3- to 10-membered heterocycle, optionally substituted with one or more substituents independently selected from a carbocycle and a C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 4’ teeth, [ka] is selected from R 5 is selected from hydrogen, hydroxy, and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 6 and R 7 are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] Forming R 20 is selected from hydrogen and optionally substituted C1-C6 alkyl; R 21 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 selected from carbocycles, R 22 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C3~10 Carbocycles, and -P(=O)(R 24 )2 is selected, R 23 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 selected from carbocycles, R 24 is an optionally substituted C1-C6 alkyl; R 100 teeth, Hydrogen and -(CH2-CH2-G) y -V, and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31, -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from is selected from R 110’ teeth, Hydrogen, -(CH2-CH2-G) y -V, -S(O)R 51’ , -S(O)2R 51’ , -C(O)R 51’ , -C(O)N(R 51’ )2, and -C(O)OR 51’ , and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31)2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from or R 100 and R 110’ together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 The ring formed by R is not an unsubstituted morpholine. 6 and R 7 is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 But together, [ka] If R 100 and R 110 is optionally further substituted with one or more =O; R 120 teeth, Hydrogen, -(CH2-CH2-G) y -V, and C 3~10 Alkyl, C2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from a carbocycle, and a 3- to 20-membered heterocycle; C 3~20 saturated carbocyclic and 3- to 20-membered heterocyclic rings, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl), or Halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31)C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 C substituted with one or more substituents independently selected from carbocycles and 3- to 20-membered heterocycles 1~2 Alkyl is selected from Each G is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each D is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each y is selected from 3 to 20; Each z is selected from 1 to 20, each V is selected from hydrogen and optionally substituted —C1-C6 alkyl; each T is selected from hydrogen and optionally substituted —C1-C6 alkyl; Each R 31 is hydrogen, as well as C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 32 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 20 , R 21 , R 22 , R 23 , R 24 , R 51’ The optional substituents on , V, and T, in each occurrence, are Halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 30 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8 Carbocycle, optionally substituted 3- to 10-membered heterocycle , -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl; q is selected from 1 to 6; each p is selected from 1 or 2; each n is selected from 3 to 7; Each W is selected from hydrogen, -OH, -C1-C4 alkyl, and -O(C1-C4 alkyl).

[0004] In certain embodiments, the present disclosure provides a method of treating a disease, comprising chronically administering a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG) to a subject in need of such treatment.

[0005] In certain embodiments, the present disclosure provides a method for treating a disease, wherein the disease is selected from a chronic disease. The chronic disease may be selected from diseases in which mTORC1 is overactivated. The chronic disease may be selected from diseases that benefit from mTORC1 inhibition. In certain embodiments, the chronic disease may be selected from neurodegenerative diseases, neurocutaneous diseases, neurodevelopmental disorders, mTORopathies, tauopathies, cognitive disorders, epilepsy, autism spectrum disorders, autoimmune diseases, metabolic diseases, cancer, autophagy disorders, infectious diseases, cardiovascular diseases, muscle atrophy, inflammatory diseases, kidney diseases, lung diseases, eye disorders, or age-related diseases that result in mTORC1 overactivation, including decreased immune activity in the elderly. The chronic disease may be an mTORopathic disease, for example, tuberous sclerosis.

[0006] In certain embodiments, the present disclosure provides a method of treating a disease, wherein the compound can be a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG).

[0007] In a second aspect, the present disclosure provides a compound represented by the structure of formula (X): [ka] or a pharmaceutically acceptable salt thereof, wherein: L is an optionally substituted C 1~8 alkylene; R 1 is a carboxylic acid or a carboxylic acid isostere, R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy groups, 3- to 10-membered heterocycles, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 4 teeth, [ka] and an optionally substituted 3- to 10-membered heterocycle, and L is selected from optionally substituted C 3~8 When R is alkylene, 4 is further selected from methoxy, -LR 1 is ethyl acetate, tert-butyl acetate, benzyl acetate, or methyl 2-phenylacetate, R 4 is not methoxy, R 4 wherein the optionally substituted heterocycle is optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, ═O, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; z is 0, 1, 2, 3, 4 or 5; R 5 is selected from hydrogen, hydroxy, and an optionally substituted C1-C6 alkoxy group, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, a C1-C6 alkoxy group, a 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 6 and R 7are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] Forming R 25 is, in each occurrence, hydrogen, optionally substituted C1-C6 alkyl, -D-(CH2-CH2-G) y -V, C substituted as needed 3~20 independently selected from a carbocycle and an optionally substituted 3- to 20-membered heterocycle; R 25 is optionally substituted C1-C6 alkyl, the substituents on the C1-C6 alkyl, at each occurrence, are halogen, —OH, —CN, —NO2, —NH2, ═O, ═S, —C(O)N(R 31 )2, -OC(O)N(R 31 )2, -C(O)OR 31 , -P(O)(R 31 )2, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, -OC 1~10 Alkyl-CN, -OC 1~10 Alkyl-C(O)OR 31 , C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~20 independently selected from a carbocycle, and a 3- to 20-membered heterocycle; R 25 C, where necessary, is replaced 3~20 When the ring is a carbocyclic ring or an optionally substituted 3- to 20-membered heterocyclic ring, C 3~20 Substituents on the carbocycle and 3- to 20-membered heterocycle, at each occurrence, are halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31, -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, and C 2~6 alkynyl; D is selected from a bond or —O—; Each G is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each y is selected from 1 to 20, each V is selected from hydrogen and optionally substituted —C1-C6 alkyl; R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is selected from the group consisting of halogen, -OH, -OSi(C1-C6 alkyl), -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R' and R'' in each occurrence are hydrogen, halogen, -OR 31 , and halogens and -OR 31 C optionally substituted with one or more substituents independently selected from 1~8 alkyl; R 31 represents hydrogen, and C in each occurrence.1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 Carbocycles and 3- to 12-membered heterocycles (each of which is selected from the group consisting of halogen, -OH, -OSi(C1-C6 alkyl), -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, -OC 1~10 Alkyl-OH, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 12-membered heterocycle; R 32 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; The substituents on V and L, in each occurrence, are Halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30)2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 30 , C 2~6 Alkenyl, and C 2~6alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from

[0008] In certain embodiments, the present disclosure provides a method of treating a disease comprising administering, e.g., chronically administering, a compound or salt of Formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG) to a subject in need of such treatment.

[0009] In certain embodiments, the present disclosure provides a method for treating a disease, wherein the disease is selected from a chronic disease. The chronic disease may be selected from diseases in which mTORC1 is overactivated. The chronic disease may be selected from diseases that benefit from mTORC1 inhibition. In certain embodiments, the chronic disease may be selected from neurodegenerative diseases, neurocutaneous diseases, neurodevelopmental disorders, mTORopathies, tauopathies, cognitive disorders, epilepsy, autism spectrum disorders, autoimmune diseases, metabolic diseases, cancer, autophagy disorders, infectious diseases, cardiovascular diseases, muscle atrophy, inflammatory diseases, kidney diseases, lung diseases, eye disorders, or age-related diseases that result in mTORC1 overactivation, including decreased immune activity in the elderly. The chronic disease may be an mTORopathic disease, for example, tuberous sclerosis.

[0010] In certain embodiments, the present disclosure provides a method of treating a disease, wherein the compound can be a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG).

[0011] In a third aspect, the present disclosure provides a compound represented by the structure of formula L: [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 teeth, [ka] , 3- to 10-membered heterocycles, and C 3~10 carbocycle, and the 3- to 10-membered heterocycle and C 3~10 The carbocyclic rings are each represented by R 33 and optionally substituted with one or more substituents independently selected from R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy groups, 3- to 10-membered heterocycles, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 4 teeth, [ka] and R 5is selected from hydrogen, hydroxy, and an optionally substituted C1-C6 alkoxy group, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, a C1-C6 alkoxy group, a 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 6 and R 7 are hydrogen, hydroxy, and C, respectively. 1~6 alkoxy, or R 6 and R 7 Let's get together and [ka] Forming R 20 is selected from hydrogen and optionally substituted C1-C6 alkyl; R 21 is selected from optionally substituted C1-C6 alkyl and optionally substituted 3- to 7-membered heterocycle; R 22 is hydrogen, optionally substituted C1-C6 alkyl, -Si(R 24 )3, and -P(=O)(R 24 )2 is selected, R 23 is selected from optionally substituted C1-C6 alkyl and optionally substituted 3- to 7-membered heterocycle; R 24 is an optionally substituted C1-C6 alkyl; R 20 , R 21 , R 22 , R 23 , and R 24The above substituents, in each occurrence, Halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 30 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from each p is selected from 1 or 2; each n is selected from 3 to 7; each W is selected from hydrogen, —OH, —C1-C4 alkyl, and —O(C1-C4 alkyl); R 30 In each occurrence, Hydrogen, and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 Carbocycles and 3- to 12-membered heterocycles (each of which is selected from the group consisting of halogen, -OH, -OSi(C1-C6 alkyl), -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 optionally substituted with one or more substituents independently selected from carbocycle, 3- to 12-membered heterocycle, and haloalkyl are independently selected from z is selected from 0 to 2; R' and R'' are hydrogen, halogen, -OR 31 , and halogens and -OR 31C optionally substituted with one or more substituents independently selected from 1~3 alkyl; Ring A is selected from optionally substituted C3-C5 carbocycles and optionally substituted 3-5 membered heterocycles, and the substituents on Ring A, at each occurrence, are Halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 31, -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from R 31 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 Carbocycles and 3- to 12-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 12-membered heterocycle; R 33 is, in each occurrence, selected from hydroxy, halogen, -CN, -NO2, ═O, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10Each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl.

[0012] In certain embodiments, the present disclosure provides a method of treating a disease, comprising chronically administering a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG) to a subject in need of such treatment.

[0013] In certain embodiments, the present disclosure provides a method for treating a disease, wherein the disease is selected from a chronic disease. The chronic disease may be selected from diseases in which mTORC1 is overactivated. The chronic disease may be selected from diseases that benefit from mTORC1 inhibition. In certain embodiments, the chronic disease may be selected from neurodegenerative diseases, neurocutaneous diseases, neurodevelopmental disorders, mTORopathies, tauopathies, cognitive disorders, epilepsy, autism spectrum disorders, autoimmune diseases, metabolic diseases, cancer, autophagy disorders, infectious diseases, cardiovascular diseases, muscle atrophy, inflammatory diseases, kidney diseases, lung diseases, eye disorders, or age-related diseases that result in mTORC1 overactivation, including decreased immune activity in the elderly. The chronic disease may be an mTORopathic disease, for example, tuberous sclerosis.

[0014] In certain embodiments, the present disclosure provides a method of treating a disease, wherein the compound can be a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG). References

[0015] All publications, patents, and patent applications mentioned herein are incorporated by reference as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent that publications and patents or patent applications incorporated by reference conflict with the present disclosure contained herein, the present specification is intended to supersede and / or take precedence over any such conflicting material. DETAILED DESCRIPTION OF THE INVENTION

[0016] Detailed Description of the Invention While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims, and their equivalents, be covered thereby. definition

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications mentioned herein are incorporated by reference.

[0018] As used in this specification and claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0019] "C x~yThe term "C" when used with a chemical moiety, such as alkyl, alkenyl, or alkynyl, is meant to include groups containing x to y carbons in the chain. For example, "C 1~6 The term "alkyl" refers to saturated hydrocarbon groups, including straight-chain and branched-chain alkyl groups, containing 1 to 6 carbons. x~y The term alkylene- refers to a substituted or unsubstituted alkylene chain having x to y carbon atoms in the alkylene chain. For example, -C 1~6 Alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.

[0020] "C x~y alkenyl" and "C x~y The term "alkynyl" refers to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one double or triple bond respectively. x~y The term alkenylene- refers to a substituted or unsubstituted alkenylene chain having x to y carbons in the alkenylene chain. For example, -C 2~6 Alkenylene- may be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. The alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. -C x~y The term alkynylene- refers to a substituted or unsubstituted alkynylene chain having x to y carbons in the alkynylene chain. For example, -C 2~6 Alkynylene- can be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. The alkynylene chain can have one triple bond or more than one triple bond within the alkynylene chain.

[0021] "Alkylene" refers to a divalent, linear hydrocarbon chain, e.g., methylene, ethylene, propylene, butylene, etc., which connects the rest of the molecule to a radical group, consists solely of carbon and hydrogen, contains no unsaturation, and preferably has 1 to 12 carbon atoms. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through their respective terminal carbons. The alkylene chain can be optionally substituted with one or more substituents, such as those described herein.

[0022] "Alkenylene" refers to a divalent, linear hydrocarbon chain, preferably having 2 to 12 carbon atoms, consisting solely of carbon and hydrogen and containing at least one carbon-carbon double bond, which connects the rest of the molecule to a radical group. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group are through their respective terminal carbons. The alkenylene chain may be optionally substituted with one or more substituents, such as those described herein.

[0023] "Alkynylene" refers to a divalent, linear hydrocarbon chain, preferably having 2 to 12 carbon atoms, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and linking the rest of the molecule to a radical group. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group are through their respective terminal carbons. The alkynylene chain may be optionally substituted with one or more substituents, such as those described herein.

[0024] The term "carbocycle," as used herein, refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocycles can include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocycle can be selected from saturated, unsaturated, and aromatic rings. In some embodiments, a carbocycle is aryl. In some embodiments, a carbocycle is cycloalkyl. In some embodiments, a carbocycle is cycloalkenyl. In an exemplary embodiment, an aromatic ring, such as phenyl, can be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings, as permitted by valence, is included in the definition of carbocycle. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. A bicyclic carbocycle can be a fused, bridged, or spiro ring system. A carbocycle may be optionally substituted with one or more substituents, such as those described herein. The term "heterocycle," as used herein, refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. A heterocycle may be attached to the remainder of the molecule through any atom of the heterocycle, such as a carbon atom or nitrogen atom of the heterocycle, as permitted by valence. In some embodiments, a heterocycle is heteroaryl. In some embodiments, a heterocycle is heterocycloalkyl. In an exemplary embodiment, a heterocycle, such as pyridyl, may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl.Bicyclic heterocycles can be fused, bridged, or spiro ring systems. The heterocycle can be optionally substituted with one or more substituents, such as those described herein.

[0025] The term "heteroaryl" includes aromatic monocyclic ring structures, preferably 5- to 7-membered rings, more preferably 5- to 6-membered rings, which ring structures contain at least one heteroatom, preferably 1-4 heteroatoms, more preferably 1 or 2 heteroatoms. The term "heteroaryl" also includes polycyclic ring systems having two or more rings, where two or more atoms are common to two adjacent rings, at least one of which may be, for example, heteroaromatic, and the other ring may be aromatic or non-aromatic carbocyclic, or heterocyclic. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine.

[0026] The term "substituted" refers to a moiety having a substituent replacing a hydrogen on one or more carbon or substitutable heteroatoms of a compound, e.g., NH or NH. It is understood that "substituted" or "substituted with" includes the implicit proviso that such substitution, subject to the allowed valences of the substituted atom and substituent, results in a stable compound, i.e., a compound that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, and the like. In certain embodiments, substituted refers to a moiety having substituents replacing two hydrogen atoms on the same carbon atom, e.g., replacing two hydrogen atoms on a single carbon with oxo, imino, or thioxo groups. As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In one broad aspect, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. The permissible substituents can be one or more and can be the same or different for appropriate organic compounds.

[0027] In some embodiments, substituents may include any substituent described herein, for example, halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO), imino (=NH), oximo (=N-OH), hydrazino (=N-NH), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a)2 (t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl (any of which may be alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=N-OH), hydrazine (=N-NH2), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2) and -R b -S(O) t N(R a)2 (t is 1 or 2), and each R a is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, and each R is as allowed by valences. a is alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=N-OH), hydrazine (=N-NH2), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2) and -R b -S(O) t N(Ra ) 2 (t is 1 or 2), and each R b are independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain; and each R c is a straight or branched alkylene, alkenylene or alkynylene chain. It will be understood by those skilled in the art that the substituents may themselves be substituted, where appropriate.

[0028] The phrases "parenteral administration" and "administered parenterally," as used herein, mean modes of administration other than enteral and topical administration, usually by injection, and include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intraarticular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0029] The phrase "pharmaceutically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0030] The phrases "pharmaceutically acceptable excipient" or "pharmaceutically acceptable carrier," as used herein, refer to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository wax; and (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, and corn oil. and soybean oil, (10) glycols, such as propylene glycol, (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol, (12) esters, such as ethyl oleate and ethyl laurate, (13) agar, (14) buffers, such as magnesium hydroxide and aluminum hydroxide, (15) alginic acid, (16) pyrogen-free water, (17) isotonic saline, (18) Ringer's solution, (19) ethyl alcohol, (20) phosphate buffer, and (21) other non-toxic compatible substances used in pharmaceutical formulations.

[0031] The terms "subject," "individual," and "patient" are used interchangeably and can refer to humans and non-human mammals (e.g., non-human primates, dogs, horses, cats, pigs, cattle, ungulates, lagomorphs, etc.). In various embodiments, a subject can be a human (e.g., an adult male, adult female, adolescent male, adolescent female, boy, girl) under the care of a physician or other medical professional in a hospital, as an outpatient, or other clinical setting. In certain embodiments, a subject may not be under the care or prescription of a physician or other medical professional.

[0032] As used herein, the phrase "subject in need thereof" refers to a subject, as defined below, suffering from or at risk of a pathology to be treated prophylactically or therapeutically with a compound or salt described herein.

[0033] The terms "administer," "administered," "administers," and "administering" are defined as providing a composition to a subject via a route known in the art, including, but not limited to, intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In certain embodiments, the oral route of administering a composition can be used. The terms "administer," "administered," "administers," and "administering" a compound should be understood to mean providing a compound of the invention or a prodrug of a compound of the invention to an individual in need.

[0034] The term "effective amount" or "therapeutically effective amount" refers to an amount of a compound or salt described herein sufficient to perform the intended application, including, but not limited to, the treatment of diseases as defined below. The therapeutically effective amount may vary depending on the intended application (in vitro or in vivo), or the subject and disease state to be treated, such as the subject's weight and age, the severity of the disease state, the mode of administration, etc., which can be easily determined by those skilled in the art. The term can also be applied to a dose that can induce a specific response in target cells, such as reducing the proliferation of or down-regulating the activity of a target protein. The specific dose may vary depending on the specific compound selected, the administration regimen to be followed, whether the compound is administered in combination with other compounds, the timing of administration, the tissue to be administered, and the physical delivery system in which the compound is carried.

[0035] As used herein, "treatment" or "treating" refers to an approach for obtaining a beneficial or desired result with respect to a disease, disorder, or condition, including, but not limited to, therapeutic benefit and / or preventative benefit. In certain embodiments, treating or treating includes administering a compound or composition disclosed herein to a subject. Therapeutic benefit can include eradication or alleviation of the underlying disorder being treated. Therapeutic benefit can also be achieved by eradicating or alleviating one or more physiological symptoms associated with the underlying disorder, such as observing an improvement in the subject, even though the subject may still be afflicted with the underlying disorder. For preventative benefit, in certain embodiments, a composition is administered to a subject at risk of developing a particular disease or reporting one or more physiological symptoms of the disease, even if a diagnosis of the disease has not been made. Treatment can include, for example, reducing, delaying, or alleviating the severity of one or more symptoms of the disease or condition, or treatment can include reducing the frequency with which a symptom of the disease, deficit, disorder, or adverse condition, etc., is experienced by the patient. Treatment may be used herein to refer to a method that results in some level of treatment or alleviation of a disease or condition, and may have a variety of outcomes aimed at that goal, including, but not limited to, prevention of the condition altogether.

[0036] In certain embodiments, the term "prevent" or "preventing," when associated with a disease or disorder, can refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in a treated sample compared to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition compared to an untreated control sample.

[0037] A "therapeutic effect," as that term is used herein, encompasses a therapeutic benefit and / or a prophylactic benefit, as described above. A prophylactic benefit includes delaying or eliminating the onset of a disease or condition, delaying or eliminating the development of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0038] The terms "selective inhibition" or "selectively inhibiting," when referring to a biologically active agent, refer to the ability of the agent to preferentially reduce target signaling activity, through direct or indirect interaction with the target, compared to off-target signaling activity. introduction

[0039] The mechanistic target of rapamycin (mTOR) signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of cellular metabolism, growth, proliferation, and survival. In particular, mTOR complex 1 (mTORC1) positively regulates cell growth and proliferation by promoting many anabolic processes, including protein, lipid, and organelle biosynthesis, and limiting catabolic processes, such as autophagy. Much of our knowledge of mTORC1 function derives from the use of the bacterial macrolide, rapamycin.

[0040] Rapamycin is thought to directly inhibit mTORC1 and indirectly inhibit mTORC2 during chronic treatment. Recent evidence has revealed that mTORC1 inhibition is responsible for effects related to lifespan extension, whereas mTORC2 inhibition is not associated with longevity and is responsible for some of the adverse effects of rapamycin, such as impaired insulin sensitivity, glucose homeostasis, and lipid dysregulation.

[0041] Studies of rapamycin and related rapalogs have revealed that these compounds form binary complexes with FKB-binding proteins, such as FKBP12 and FKBP51. This binary complex can allosterically inhibit the function of mTORC1 by binding to the FRB domain of mTOR. FKBP12 and FKBP51 direct binding assays provide a method for assessing the relative binding affinity of rapalogs to specific FKBPs. Without being bound by any particular mechanistic theory, it may be preferable that the binding of rapalogs to FKB proteins, such as FKBP12 or FKBP51, is similar, equivalent, or stronger than that of rapamycin to the FKB proteins.

[0042] The ternary complex formation assay provides a method for assessing the relative binding affinities of rapalog / FKB binary complexes to the FRB domain of mTOR. The different binding affinities for mTOR exhibited by rapalog / FKB complexes may result in different pharmacological and safety profiles compared to the known rapalogs, rapamycin and everolimus.

[0043] In certain aspects, the present disclosure provides compounds and their salts, and methods for use in treating diseases.In certain embodiments, the compounds described herein are called rapalogs, and rapalogs refer to the shared core structure of the compounds described herein compared with rapamycin.In certain aspects, the compounds described herein show similar direct binding properties, such as similar or improved FKB binding, compared with known compounds such as rapamycin and everolimus.In certain aspects, the compounds described herein show changes in ternary binding affinity, such as reduced binding affinity to the FRB domain of mTOR, compared with known compounds such as rapamycin or everolimus.

[0044] In certain embodiments, compounds or salts of the present disclosure are evaluated for direct binding to FKBP12 and / or FKBP51. In certain embodiments, compounds or salts of the present disclosure are evaluated for ternary complex formation with MTORC1 and FKBP12. In certain embodiments, the compound or salt thereof has strong binding to FKBP12 and / or FKBP51.

[0045] In certain embodiments, the compounds of the present disclosure are classified into compound groups 1, 2, and 3. Each of these compound groups describes a distinct chemical structure classification. Any duplication of a variable in one group with another group is not intended to imply that the variable is interchangeable with one variable in the other group. For example, R in the compounds of group 1 1 applies only to Group 1 compounds and not to Group 2 or Group 3 compounds. Compound group 1

[0046] In a first aspect, the present disclosure provides a compound represented by the structure of Formula I: [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 is -OH, [ka] , 3- to 10-membered heterocycles, and C 3~10 carbocycle, and the 3- to 10-membered heterocycle and C 3~10 The carbocycles are each selected from the group consisting of hydroxy, halogen, -CN, -NO2, ═O, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 alkoxy, 3- to 10-membered heterocycles, and C 3~10 and a 3- to 10-membered heterocycle, optionally substituted with one or more substituents independently selected from a carbocycle and a C 3~10each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 4’ teeth, [ka] is selected from R 5 is selected from hydrogen, hydroxy, and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 6 and R 7 are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] Forming R 20 is selected from hydrogen and optionally substituted C1-C6 alkyl; R 21 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 selected from carbocycles, R 22 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 Carbocycles, and -P(=O)(R 24 )2 is selected, R 23 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 selected from carbocycles, R 24 is an optionally substituted C1-C6 alkyl; R 100 teeth, Hydrogen and -(CH2-CH2-G) y -V, and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from is selected from R 110’ teeth, Hydrogen, -(CH2-CH2-G) y -V, -S(O)R 51’ , -S(O)2R 51’ , -C(O)R 51’ , -C(O)N(R 51’ )2, and -C(O)OR51’ , and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from or R 100 and R110’ together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 The ring formed by R is not an unsubstituted morpholine. 6 and R 7 is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 But together, [ka] If R 100 and R 110 is optionally further substituted with one or more =O; R 120 teeth, Hydrogen, -(CH2-CH2-G) y -V, and C 3~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 20-membered heterocycle, and C 3~20 saturated carbocyclic and 3- to 20-membered heterocyclic rings, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl), or Halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 C substituted with one or more substituents independently selected from carbocycles and 3- to 20-membered heterocycles 1~2 Alkyl is selected from Each G is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each D is -O-, -NR32 independently selected from -, -S-, or -SO2-; Each y is selected from 3 to 20; Each z is selected from 1 to 20, each V is selected from hydrogen and optionally substituted —C1-C6 alkyl; each T is selected from hydrogen and optionally substituted —C1-C6 alkyl; Each R 31 is hydrogen, as well as C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 32 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 20 , R 21 , R 22 , R 23 , R 24 , R 51’The optional substituents on , V, and T, in each occurrence, are Halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 30 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8 Carbocycle, optionally substituted 3- to 10-membered heterocycle, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl; q is selected from 1 to 6; each p is selected from 1 or 2; each n is selected from 3 to 7; Each W is selected from hydrogen, -OH, -C1-C4 alkyl, and -O(C1-C4 alkyl).

[0047] In some embodiments, the compound of formula (I) has the formula (IZ) [ka] or a pharmaceutically acceptable salt thereof, R 1 is -OH, [ka] , 3- to 10-membered heterocycles, and C 3~10 carbocycle, and the 3- to 10-membered heterocycle and C 3~10 The carbocycles are each selected from the group consisting of hydroxy, halogen, -CN, -NO2, ═O, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 alkoxy, 3- to 10-membered heterocycles, and C 3~10 and a 3- to 10-membered heterocycle, optionally substituted with one or more substituents independently selected from a carbocycle and a C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 4 teeth, [ka] is selected from R 5 is selected from hydrogen, hydroxy, and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 6 and R 7 are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] Forming R 20 is selected from hydrogen and optionally substituted C1-C6 alkyl; R 21is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 selected from carbocycles, R 22 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 Carbocycles, and -P(=O)(R 24 )2 is selected, R 23 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 selected from carbocycles, R 24 is an optionally substituted C1-C6 alkyl; R 100 teeth, Hydrogen and -(CH2-CH2-G) y -V, and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31, -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from is selected from R 110 teeth, Hydrogen, -(CH2-CH2-G) y -V, -S(O)R 51 , -S(O)2R 51 , -C(O)R 51 , -C(O)N(R 51 )2, and -C(O)OR 51 , and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from or R 100 and R 110 together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 The ring formed by R is not an unsubstituted morpholine. 6 and R 7 one of which is selected from hydroxy and C1-C6 alkoxy; or R 6 and R 7 But together, [ka] If R 100 and R 110 is optionally further substituted with one or more =O; R 120 teeth, Hydrogen, -(CH2-CH2-G) y -V, and C 3~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 20-membered heterocycle, and C 3~20 saturated carbocyclic and 3- to 20-membered heterocyclic rings, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl), or Halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 C substituted with one or more substituents independently selected from carbocycles and 3- to 20-membered heterocycles 1~2 Alkyl is selected from Each G is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each D is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each y is selected from 3 to 20; Each z is selected from 1 to 20, each V is selected from hydrogen and optionally substituted —C1-C6 alkyl; each T is selected from hydrogen and optionally substituted —C1-C6 alkyl; Each R 31 is hydrogen, as well as C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 32 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 20 , R 21 , R 22 , R 23 , R 24 , R 51 The optional substituents on , V, and T, in each occurrence, are Halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 30 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 51 In each occurrence, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl; q is selected from 1 to 6; each p is selected from 1 or 2; each n is selected from 3 to 7; Each W is selected from hydrogen, -OH, -C1-C4 alkyl, and -O(C1-C4 alkyl).

[0048] In certain embodiments, the compound of formula (I) has the formula (IA) [ka] or a salt thereof.

[0049] In certain embodiments, the compound of formula (I) has the formula (IB): [ka] or a salt thereof.

[0050] In certain embodiments, the compound of formula (I) has the formula (IC) [ka] or a salt thereof.

[0051] In certain embodiments, the compound of formula (I) has the formula (ID): [ka] or a salt thereof.

[0052] In certain embodiments, the compound of formula (I) has the formula (IE) [ka] or a salt thereof.

[0053] In certain embodiments, the compound of formula (I) has the formula (IF): [ka] or a salt thereof.

[0054] In certain embodiments, the compound of formula (I) has the formula (IG) [ka] or a salt thereof.

[0055] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is R 51 is expressed by

[0056] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 100’ is R 100 is expressed by

[0057] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4’ is R 4is.

[0058] In some embodiments of a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), [ka] teeth, [ka] is expressed by

[0059] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 100 and R 110’ together with the nitrogen to which they are attached form a 3-10 membered heteroaryl optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy.

[0060] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 100 and R 110’ together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 The ring formed by is not an unsubstituted morpholine.

[0061] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R100 and R 110’ together with the nitrogen to which they are attached form a 3-5 membered saturated heterocycle optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy.

[0062] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 6 and R 7 But together, [ka] Form R 1 is hydroxy, R 4 teeth, [ka] Instead, R 6 and R 7 But together, [ka] Form R 1 but, [ka] If R 4 teeth, [ka] In some cases, R 4 teeth, [ka] In some cases, R 4 teeth, [ka] In some cases, R 4 teeth, [ka] In some cases, R 4 teeth, [ka] That's not possible.

[0063] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 100 and R 110’ do not form a 3- to 10-membered ring together with the nitrogen to which they are attached.

[0064] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] In some embodiments, R 100 is R 110 are selected from the same parts as R 100 is ethyl, and R 110 is ethyl. In some embodiments, R 100 is R 110 In some embodiments, R 100 is H. In some embodiments, R 110 is -(CH2-CH2-G) y -V, as well as halogens, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 20-membered heterocycles 1~10 alkyl.

[0065] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 110 is -(CH2-CH2-G) y In some embodiments, the compound is selected from -(CH2-CH2-G) y In -V, y is 1 to 1000. In some embodiments, y is 1 to 800. In some embodiments, y is 1 to 500. In some embodiments, y is 1 to 300. In some embodiments, y is 1 to 100. In some embodiments, y is 1 to 50. In some embodiments, y is 1 to 25. In some embodiments, y is 3 to 1000. In some embodiments, y is 10 to 1000. In some embodiments, y is 50 to 1000. In some embodiments, y is 100 to 1000. In some embodiments, y is 200 to 1000. In some embodiments, y is 500 to 1000. In some embodiments, R 110 -(CH2-CH2-G) y -V, y is 3 to 10. In some embodiments, R 110 -(CH2-CH2-G) y -V's y is 5 to 10. In some embodiments, y is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100.

[0066] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 110 is -(CH2-CH2-G) y -V, -(CH2-CH2-G) y G in -V is -O-. In some embodiments, R 110 -(CH2-CH2-G) y Each G in -V is -NR 32 In some embodiments, -NR 32 -Each R 32 is hydrogen, and C 1~10 Alkyl (each of which is a halogen, -OH, C 1~10 Alkyl, -C 1~10 Haloalkyl, and -OC 1~10 and optionally substituted with one or more substituents independently selected from alkyl.

[0067] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 110 is -(CH2-CH2-G) y -V is selected from R 110 Each V is optionally substituted -C1 to -C 10 In some embodiments, R 110 Each V in R is an optionally substituted -C1-C6 alkyl. 110 -C1-C6 alkyl on V is halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p )n -W, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and —CN.

[0068] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 110 -C1-C6 alkyl on V is -OR 30 and -N(R 30 )2. In some embodiments, R 110 The -C1-C6 alkyl on V may be one or more -N(R 30 In some embodiments, R 110 The -C1-C6 alkyl on V may be one or more -OR 30 In some embodiments, each R 30 is hydrogen, as well as C 1~5 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, and -OC 1~10 optionally substituted with one or more substituents independently selected from alkyl.

[0069] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R4 teeth, [ka] and [ka] R 100 and R 110 together with the nitrogen to which they are attached form a 3-, 4-, 5-, 7-, or 8-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C-C alkyl, C-C haloalkyl, C-C hydroxyalkyl, and C-C alkoxy. In some embodiments, the 3- to 8-membered heterocyclic ring is unsaturated. In some embodiments, the 3- to 8-membered heterocyclic ring is saturated.

[0070] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 and R 110 together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 The ring formed by R is not an unsubstituted morpholine. 6 and R 7 is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 But together, [ka] If R 100 and R 110 The 3-10 membered heterocycle formed by is further optionally substituted with one or more =O.

[0071] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 and R 110 together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 is a substituted morpholine, R 6 and R 7 is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 But together, [ka] If R 100 and R 110 The 3-10 membered heterocycle formed by is further optionally substituted with one or more =O.

[0072] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 and R 110 together with the nitrogen to which they are attached form a heterocycle. The heterocycle can be selected from a 3- to 10-membered heterocycle, a 3- to 8-membered heterocycle, a 3- to 6-membered heterocycle, a 3- to 5-membered heterocycle, a 4- to 10-membered heterocycle, a 4- to 8-membered heterocycle, a 4- to 6-membered heterocycle, and a 4- to 5-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C-C alkyl, C-C haloalkyl, C-C hydroxyalkyl, ═O, and C-C alkoxy. In some embodiments, the heterocycle is optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C-C alkyl, C-C haloalkyl, C-C hydroxyalkyl, and C-C alkoxy. In some embodiments, the heterocycle is optionally substituted with one or more substituents selected from hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, =O, and C1-C6 alkoxy. In some embodiments, the heterocycle is unsaturated. In some embodiments, the heterocycle is saturated. In some embodiments, the heterocycle is aromatic. In some embodiments, the heterocycle further comprises at least a second heteroatom. In some embodiments, the second heteroatom is selected from nitrogen, oxygen, and sulfur. In some embodiments, the second heteroatom is selected from nitrogen and sulfur. In some embodiments, the second heteroatom is selected from oxygen and sulfur. In some embodiments, the second heteroatom is selected from nitrogen and oxygen. In some embodiments, the second heteroatom is sulfur. Some embodiments In some embodiments, the second heteroatom is nitrogen. In some embodiments, the second heteroatom is oxygen.

[0073] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 and R 110 together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 The ring formed by [ka] Instead, R 6 and R 7 is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 But together, [ka] If R 100 and R 110 The 3-10 membered heterocycle formed by is further optionally substituted with one or more =O.

[0074] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110together with the nitrogen to which they are attached form aziridine, 2H-azirine, azetidine, 2,3-dihydroazete, 1,3-diazetidine, pyrrolidine, 2-pyrroline, 2H-pyrrole, 1H-pyrrole, pyrazolidine, imidazolidine, 2-pyrazoline, 2-imidazoline, pyrazole, imidazole, 1,2,4-triazole, 1,2,3-triazole, tetrazole, oxazole, isoxazole, isothiazole, thiazole, 1,2,5-oxadiazole, 1,2,3-oxadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, 2,4-thiazolidinedione, succinimide, oxazine, thiomorpholine, thiazine, 2-oxazolidone , hydantoin, cytosine, thymine, uracil, thiomorpholine dioxide, piperidine, pyridine, piperazine, pyridazine, pyrimidine, pyrazine, triazine, 2,3-dihydroazepine, 2,5-dihydroazepine, 4,5-dihydroazepine, azepine, 2H-azepine, 3H-azepine, 4H-azepine, 1,2-diazepine, 1,3-diazepine (dizepine), 1,4-diazepine, 1,4-thiazepine, azocane, and azocine, each of which is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy.

[0075] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110together with the nitrogen to which they are attached, form aziridine, 2H-azirine, azetidine, 2,3-dihydroazate, 1,3-diazetidine, pyrrolidine, 2-pyrroline, 2H-pyrrole, 1H-pyrrole, pyrazolidine, imidazolidine, 2-pyrazoline, 2-imidazoline, pyrazole, imidazole, 1,2,4-triazole, 1,2,3-triazole, tetrazole, oxazole, isoxazole, isothiazole, thiazole, 1,2,5-oxadiazole, 1,2,3-oxadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, 2,4-thiazolidinedione, succinimide, oxazine, thiomorpholine, thiazine, 2-oxazolidone, hydantoin, cytosine, thymine , uracil, thiomorpholine dioxide, piperidine, pyridine, piperazine, pyridazine, pyrimidine, pyrazine, triazine, 2,3-dihydroazepine, 2,5-dihydroazepine, 4,5-dihydroazepine, azepine, 2H-azepine, 3H-azepine, 4H-azepine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, 1,4-thiazepine, azocane, azocine, 1,2-thiazetidine, isothiazolidine, and imidazolidine, each of which is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy.

[0076] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110together with the nitrogen to which they are attached, form aziridine, 2H-azirine, azetidine, 2,3-dihydroazate, 1,3-diazetidine, pyrrolidine, 2-pyrroline, 2H-pyrrole, 1H-pyrrole, pyrazolidine, imidazolidine, 2-pyrazoline, 2-imidazoline, pyrazole, imidazole, 1,2,4-triazole, 1,2,3-triazole, tetrazole, oxazole, isoxazole, isothiazole, thiazole, 1,2,5-oxadiazole, 1,2,3-oxadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, 2,4-thiazolidinedione, succinimide, oxazine, thiomorpholine, thiazine, 2-oxazolidone, hydantoin, cytosine, thymine, and imidazolidine, each of which is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, ═O, and C1-C6 alkoxy.

[0077] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 is R 6 and R 7is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 But together, [ka] together with the nitrogen to which they are attached form azetidine, 1,2-thiazetidine, isothiazolidine, and imidazolidine, each of which is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, ═O.

[0078] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 together with the nitrogen to which they are attached, [ka] Form R 6 and R 7 is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] Form.

[0079] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 is R 6 and R 7 is selected from hydroxy and C1-C6 alkoxy, or R 6 and R 7 But together, [ka] When they form, together with the nitrogen to which they are attached, [ka] Form.

[0080] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 together with the nitrogen to which they are attached, [ka] Form R 1 teeth, [ka] Not selected from.

[0081] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 is R 1 but, [ka] When they are not selected from, together with the nitrogen to which they are attached, [ka] Form.

[0082] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 is R 1 but, [ka] When they are not selected from, together with the nitrogen to which they are attached, [ka] Form.

[0083] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 is R 1 but, [ka] When they are not selected from, together with the nitrogen to which they are attached, [ka] Form.

[0084] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and [ka] R 100 and R 110 together with the nitrogen to which they are attached form azetidin-2-one, thizetidine 1,1-dioxide, or isothiazolidine 1,1 -dioxide, either of which is substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy.

[0085] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 is hydrogen or C 1~10 alkyl, and R 110 is -(CH2-CH2-G) y -V, -S(O)R 51 , -S(O)2R 51 , -C(O)R 51 , -C(O)N(R 51 )2, and -C(O)OR 51 or R 100 and R 110 together with the nitrogen to which they are attached form a 3-10 membered heterocycle optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy, and ═O.

[0086] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 is hydrogen or C 1~10 alkyl, and R 110 is -(CH2-CH2-G) y -V, -S(O)R 51 , and -S(O)R 51 or R 100 and R 110together with the nitrogen to which they are attached form a 3-10 membered heterocycle optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy, and ═O.

[0087] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 is hydrogen or C 1~10 alkyl, and R 110 is -S(O)R 51 , and -S(O)R 51 or R 100 and R 110 together with the nitrogen to which they are attached form a 3-10 membered heterocycle optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy, and ═O.

[0088] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 is hydrogen or C 1~10 alkyl, and R 110 is -S(O)R 51 , and -S(O)R 51 or R 100 and R 110together with the nitrogen to which they are attached form a 3-10 membered heterocycle optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy, and ═O.

[0089] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51 In each occurrence, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl; q in each occurrence is independently selected from 1 to 6; and each D is -O-, -NR 32 In some embodiments, R is independently selected from -, -S-, or -SO2-, where each z is selected from 1 to 20, and each T is selected from hydrogen and optionally substituted -C1-C6 alkyl. 51 In each occurrence, -((CH2) q -CH2-D) z In some embodiments, R 51 is replaced as necessary 5~30 In some embodiments, q is alkyl. In some embodiments, q, at each occurrence, is independently selected from 1 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2. In some embodiments, q is 1 to 5. In some embodiments, q is 1 to 4. In some embodiments, q is 1 to 3. In some embodiments, q is 1 to 2. In some embodiments, q is 6. In some embodiments, q is 5. In some embodiments, q is 4. In some embodiments, q is 3. In some embodiments, q is 2. In some embodiments, q is 1. In some embodiments, D, at each occurrence, is selected from -O-, -NR 32 In some embodiments, D is independently selected from -O-, -NR32 In some embodiments, D is independently selected from -O- or -NR 32 In some embodiments, D, at each occurrence, is independently selected from -O-. In some embodiments, z is selected from 1 to 500. In some embodiments, z is selected from 1 to 50. In some embodiments, z is selected from 1 to 300. In some embodiments, z is selected from 3 to 500. In some embodiments, z is selected from 3 to 250. In some embodiments, z is selected from 3 to 50. In some embodiments, z is selected from 3 to 25. In some embodiments, z is selected from 3 to 20. In some embodiments, z is selected from 3 to 10. In some embodiments, z is selected from 3. In some embodiments, z is selected from 20. In some embodiments, T is selected from hydrogen and optionally substituted -C1-C6 alkyl. In some embodiments, T is hydrogen. In some embodiments, T is selected from optionally substituted -C1-C6 alkyl. In some embodiments, T is selected from unsubstituted -C1-C6 alkyl. In some embodiments, -NR 32 -R 32 is hydrogen and C 1~10 In some embodiments, R 4 teeth, [ka] In some embodiments, —NR 32 -R 32 is hydrogen. In some embodiments, —NR 32 -R 32 is C 1~10 alkyl.

[0090] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51 In each occurrence, -((CH2) q-CH2-D) z -T and optionally substituted C 5~30 alkyl; q in each occurrence is independently selected from 1 to 6; and each D is -O-, -NR 32 each z is selected from 1 to 20; and each T is selected from hydrogen and optionally substituted —C1 to C6 alkyl.

[0091] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51 In each occurrence, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl; q in each occurrence is independently selected from 1 to 6; and each D is -O-, -NR 32 In some embodiments, R is independently selected from -, -S-, or -SO2-, each z is selected from 3 to 20, and each T is selected from hydrogen and optionally substituted -C1-C6 alkyl. 51 is replaced as necessary 5~30 In some embodiments, R 51 is C 5~30 alkyl, C 5~30 Alkyl is optionally substituted C 5~25 Alkyl, optionally substituted C 5~20 Alkyl, optionally substituted C 5~15 Alkyl and optionally substituted C 5~10 In some embodiments, R 51 is replaced as necessary 5~10 In some embodiments, C 5~30 Alkyl is halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and —CN. In some embodiments, C 5~30 Alkyl is -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , —NO2, and —CN. 5~30 Alkyl is -OR 30 In some embodiments, each R 30 In each occurrence, hydrogen and C 1~10 In some embodiments, -OR is independently selected from alkyl. 30 R 30 is hydrogen and C 1~10 In some embodiments, -OR is independently selected from alkyl. 30 R 30 is C 1~10 alkyl.

[0092] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R51 is C 3~8 In some embodiments, R 51 is C 3~6 In some embodiments, R 51 is C 3~6 cycloalkyl.

[0093] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 100 is hydrogen or C 1~10 alkyl, and R 110 is -S(O)2R 51 or R 100 and R 110 together with the nitrogen to which they are attached form a 3-10 membered heterocycle optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy, and ═O.

[0094] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 100 and R 110 Furthermore, R 1 is not hydroxy, -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31)2, -OP(O)(OR 31 )2, -NO2, -CN, optionally substituted C 3~20 In some embodiments of the compounds or salts of Formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 100 and R 110 Furthermore, R 1 is not hydroxy, -S(O)R 31 , -S(O)2R 31 , -NO2, -CN, optionally substituted C 3~20 In some embodiments, R is independently selected from carbocycle and optionally substituted 3- to 20-membered heterocycle. 100 and R 110 Furthermore, R 1 is not hydroxy, -S(O)R 31 and -S(O)R 31 In some embodiments, each R 31 represents hydrogen, and C 1~10 alkyl, 1~10 Alkyl is a halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, and -OC 1~10 and optionally substituted with one or more substituents independently selected from alkyl. 1~10 Alkyl is -OC 1~10 and optionally substituted with one or more substituents independently selected from alkyl.

[0095] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] In some embodiments, R4 R 120 is hydrogen, -(CH2-CH2-G) y -V; and halogens, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, -CN, C 3~20 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 20-membered heterocycles 3~10 Alkyl; and C 3~20 saturated carbocyclic and 3- to 20-membered heterocyclic rings, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from:

[0096] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 4 R 120 is hydrogen.

[0097] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 4 R 120 is -(CH2-CH2-G) y -V.

[0098] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 4 R 120 is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, -CN, C 3~20 C optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle 3~10 In some embodiments, R 4 R 120 -OR 31 , -SR 31 , and -N(R 31 ) C optionally substituted with one or more substituents independently selected from 3~10 alkyl, and each R 31 is hydrogen, as well as C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10are independently selected from carbocycles and 3- to 10-membered heterocycles.

[0099] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 4 R 120 is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 C substituted with one or more substituents independently selected from carbocycles and 3- to 20-membered heterocycles 1~2 It is alkyl.

[0100] For compounds or salts of Formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), in some embodiments for compounds or salts of Formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] and R 120 is -(CH2-CH2-G) y -V is selected from R 120 -(CH2-CH2-G) yIn -V, y is 1 to 1000. In some embodiments, y is 1 to 800. In some embodiments, y is 1 to 500. In some embodiments, y is 1 to 300. In some embodiments, y is 1 to 100. In some embodiments, y is 1 to 50. In some embodiments, y is 1 to 25. In some embodiments, y is 3 to 1000. In some embodiments, y is 10 to 1000. In some embodiments, y is 50 to 1000. In some embodiments, y is 100 to 1000. In some embodiments, y is 200 to 1000. In some embodiments, y is 500 to 1000. In some embodiments, R 120 -(CH2-CH2-G) y -V, y is 3 to 10. In some embodiments, R 120 -(CH2-CH2-G) y -V's y is 5 to 10. In some embodiments, y is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100.

[0101] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, wherein the substituents at each occurrence are independently selected from hydroxy, halogen, —CN, —NO2, and C1-C6 alkoxy. 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents at each occurrence being independently selected from hydroxy, halogen, —NO2, and C1-C6 alkoxy.

[0102] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 2 is selected from hydrogen and C1-C6 alkoxy.2 is selected from hydrogen and -OMe. 2 is -OMe.

[0103] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents at each occurrence being independently selected from hydroxy and C1-C6 alkoxy. 3 is selected from hydrogen and C1-C6 alkoxy.

[0104] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 3 is selected from C1-C6 alkoxy. 3 is -OMe.

[0105] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 5 is selected from hydrogen, hydroxy, and optionally substituted C1-C6 alkoxy, wherein the substituents at each occurrence are independently selected from hydroxy, halogen, —CN, —NO2, and C1-C6 alkoxy.

[0106] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 5 is hydroxy.

[0107] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 6 and R 7are each independently selected from hydrogen and hydroxy. 6 and R 7 are each hydrogen. 6 is hydrogen and R 7 is hydroxy. In some embodiments, R 6 and R 7 Let's get together and [ka] Form.

[0108] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] In some embodiments of the compounds or salts of Formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is selected from hydroxy.

[0109] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] , with C being substituted as needed 3~10 It is selected from carbocycles and optionally substituted 3- to 10-membered heterocycles.

[0110] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] and optionally substituted 3- to 10-membered heterocycles.

[0111] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is selected from -OH.

[0112] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is -OH, [ka] , optionally substituted 3- to 10-membered heterocycles, and optionally substituted C 3~10 Carbocycles are selected from:

[0113] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is -OH, [ka] and optionally substituted 3- to 10-membered heterocycles.

[0114] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1is an optionally substituted 3- to 10-membered heterocycle. In some embodiments, the optionally substituted heterocycle is a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycle. In some embodiments, the optionally substituted 3- to 10-membered heterocycle is a 3- or 4-membered heterocycle, a 5- or 6-membered heterocycle, a 7- or 8-membered heterocycle, or a 9- or 10-membered heterocycle.

[0115] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is an optionally substituted 5-6 membered heterocycle containing at least one heteroatom selected from oxygen, nitrogen, sulfur, boron, phosphorous, silicon, selenium, and any combination thereof. In some embodiments, the optionally substituted 5-6 membered heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, and any combination thereof.

[0116] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 The optionally substituted 5- to 6-membered heterocycle of formula (I) contains at least one nitrogen. 1 The optionally substituted 5- to 6-membered heterocycle is [ka] any of which is selected from hydroxy, halogen, —CN, —NO2, ═O, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, a 3-10 membered heterocycle, and C 3~10 and a 3- to 10-membered heterocycle, optionally substituted with one or more substituents independently selected from a carbocycle and a C 3~10Each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, -CN, -NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy. In some embodiments, the one or more substituents are selected from hydroxy, ═O, C1-C6 alkyl, 3-8 membered heterocycle, and C 3~8 carbocycle, wherein the 3-8 membered heterocycle and C 3~8 Each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy.

[0117] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is an optionally substituted C1-C6 alkyl, and -P(=O)(R 24 )2 is selected.

[0118] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is hydrogen.

[0119] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is -P(=O)(R 24)2 and R 24 is replaced as necessary 1~10 In some embodiments, R 1 teeth, [ka] is.

[0120] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -OR 30 , with C being substituted as needed 3~10 C1-C6 alkyl optionally substituted with one or more substituents selected from carbocycle and optionally substituted 3- to 10-membered heterocycle; R 30 is hydrogen and optionally substituted C 1~10 In some embodiments, R 1 R 22 is -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, and -OR 30 is a C1-C6 alkyl substituted with one or more substituents selected from:

[0121] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is -N(R 30 )2. In some embodiments, R 1 teeth, [ka] is.

[0122] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is -(O-CH2-(CH2) p ) n and n is 1 to 1000. In some embodiments, n is 1 to 800. In some embodiments, n is 1 to 500. In some embodiments, n is 1 to 300. In some embodiments, n is 1 to 100. In some embodiments, n is 1 to 50. In some embodiments, n is 1 to 25. In some embodiments, n is 3 to 1000. In some embodiments, n is 10 to 1000. In some embodiments, n is 50 to 1000. In some embodiments, n is 100 to 1000. In some embodiments, n is 200 to 1000. In some embodiments, n is 500 to 1000. In some embodiments, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100. In some embodiments, p is 1 to 1000. In some embodiments, p is 1 to 800. In some embodiments, p is 1 to 500. In some embodiments, p is 1 to 300. In some embodiments, p is 1 to 100. In some embodiments, p is 1 to 50. In some embodiments, p is 1 to 25. In some embodiments, p is 3 to 1000. In some embodiments, p is 10 to 1000. In some embodiments, p is 50 to 1000. In some embodiments, p is 100 to 1000. In some embodiments, p is 200 to 1000. In some embodiments, p is 500 to 1000. In some embodiments, p is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100.

[0123] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is -(O-CH2-(CH2) p ) n -W, and -OR 30 In some embodiments, R is a C1-C6 alkyl substituted with one or more substituents selected from 1 teeth, [ka] is selected from.

[0124] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is replaced as necessary 3~10 In some embodiments, optionally substituted C 3~10 Carbocyclic rings are C 3~6 In certain embodiments, C 3~6 The carbocyclic ring is unsaturated. 3~6 Carbocycles are saturated. In some embodiments, optionally substituted C 3~6 Carbocycles are: [ka] In some embodiments, R 1 R 22 is C1-C6 alkyl substituted with phenyl. In some embodiments, R 1 teeth, [ka] is selected from.

[0125] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 22 is a C1-C6 alkyl substituted with one or more substituents selected from an optionally substituted 3-6 membered heterocycle. In some embodiments, the optionally substituted 3-6 membered heterocycle contains at least one heteroatom selected from N, O, S, and any combination thereof.

[0126] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 22 is C1-C6 alkyl substituted with one or more substituents selected from optionally substituted 3-8 membered heterocycles. 22 is a C2-C3 alkyl substituted with one or more substituents selected from an optionally substituted 3-8 membered heterocycle. 1 R 22 is a C1-C6 alkyl substituted with one or more substituents selected from an optionally substituted 3-8 membered heterocycle, wherein the optionally substituted 3-8 membered heterocycle contains at least one heteroatom selected from N and O. In some embodiments, R 22 In some embodiments, the 3-8 membered heterocycle of R 22 The 3- to 8-membered heterocycle is -S(O)R 30 , C 1~6 Alkyl and -OR 30 In some embodiments, the compound is substituted with one or more substituents selected from: 30 R 30 is C 1~10 alkyl, -OR 30 R 30 is hydrogen and C 1~6 In some embodiments, R 1 R 22is a C1-C6 alkyl substituted with one or more substituents selected from an optionally substituted 3-6 membered heterocycle, wherein the optionally substituted 3-6 membered heterocycle contains at least one heteroatom selected from N and O. In some embodiments, the 3-6 membered heterocycle is an optionally substituted C 1~6 Alkyl and -OR 30 In some embodiments, R 1 teeth, [ka] is selected from.

[0127] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] [ka] is selected from.

[0128] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] is selected from.

[0129] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] In some embodiments, R 1 R20 is selected from hydrogen and optionally substituted C1-C3 alkyl. In some embodiments, R 1 R 21 is selected from hydrogen and optionally substituted C1-C3 alkyl. In some embodiments, R 1 R 21 is replaced as necessary 1~10 In some embodiments, R 1 R 21 -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, C substituted as needed 3~10 C substituted with one or more substituents selected from carbocycles and optionally substituted 3- to 10-membered heterocycles 1~10 In some embodiments, R 1 teeth, [ka] is selected from.

[0130] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] and R 1 R 21 is an optionally substituted 3- to 7-membered heterocycle. In some embodiments, the 3- to 7-membered heterocycle is -OR 30 and C, substituted as needed 1~10 In some embodiments, R is substituted with one or more substituents selected from alkyl. 1 teeth, [ka] is selected from.

[0131] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] In some embodiments, R 1 R 23 is an optionally substituted C1-C6 alkyl. In some embodiments, C1-C6 alkyl is —OR 30 , -N(R 30 )2, optionally substituted C 1~10 Alkyl, optionally substituted C 3~10 In some embodiments, R is substituted with one or more substituents selected from a carbocycle and a 3- to 10-membered heterocycle. 1 teeth, [ka] is selected from.

[0132] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 R 23 is an optionally substituted 3- to 7-membered heterocycle. In some embodiments, the 3- to 7-membered heterocycle is optionally substituted C 1~10 In some embodiments, R is substituted with one or more substituents selected from alkyl. 1 teeth, [ka] is selected from.

[0133] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] [ka] [ka] is selected from.

[0134] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] [ka] is selected from.

[0135] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] [ka] is selected from.

[0136] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] is selected from.

[0137] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1teeth, [ka] is selected from.

[0138] In some embodiments of a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] is selected from R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, such as R 2 is a C1-C6 alkoxy group, preferably R 2 is -OCH3, R 3 is selected from optionally substituted C1-C6 alkoxy groups, such as R 3 is a C1-C6 alkoxy group, preferably R 3 is -OCH3, R 4’ teeth, [ka] is selected from R 5 is selected from hydroxy and optionally substituted C1-C6 alkoxy, such as R 5 is a C1-C6 alkoxy group, preferably R 5 is hydroxy, R 6 and R 7 Let's get together and [ka] Forming R 22 is selected from C1-C6 alkyl, for example, R 22is a C2-C4 alkyl, and the C1-C6 alkyl or C2-C4 alkyl is an optionally substituted 3-8 membered saturated heterocycle, oxo, -OC 1~10 Alkyl, -NR 30 -S(O)2R 30 , -SO2-N(R 30 )2, or -S(O)2R 30 is substituted with R 22 The substituents on the 3- to 8-membered saturated heterocyclic ring are -NR 52 -SO2-R 30 , -SO2-N(R 52 )2, -S(O)2R 30 , C 1~6 Alkyl, C 1~6 Hydroxyalkyl, and -OR 30 independently selected from -S(O)R 30 R 30 is C 1~10 alkyl, -OR 30 R 30 is hydrogen and C 1~6 alkyl, R 100 is hydrogen and C 1~10 alkyl, R 110’ is -S(O)2R 51’ Selected from R 51’ is a substitution C 1~4 Alkyl, -((CH2) q -CH2-D) z -T, C substituted as needed 1~30 Alkyl, optionally substituted C 3~8 selected from carbocycles and optionally substituted 3- to 10-membered heterocycles; R 52 is hydrogen and C 1~10 alkyl, R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; q is selected from 1 to 6; Each z is selected from 1 to 20, Each T is selected from hydrogen and optionally substituted -C1-C6 alkyl.

[0139] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ In each occurrence, -((CH2) q -CH2-D) z -T, C substituted as needed 1~30 Alkyl, optionally substituted C 3~8 In some embodiments, R is independently selected from a carbocycle, and an optionally substituted 3- to 10-membered heterocycle. 51’ In each occurrence, -((CH2) q -CH2-D) z -T, C substituted as needed 3~8 In some embodiments, R is independently selected from a carbocycle, and an optionally substituted 3- to 10-membered heterocycle. 51’ In each occurrence, -((CH2) q -CH2-D) z -T, C 3~8 are independently selected from carbocycles, and 3- to 10-membered heterocycles.

[0140] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’is -((CH2) q -CH2-D) z In some embodiments, R 51’ is C 1~30 In some embodiments, R 51’ is the unsubstituted C 1~30 In some embodiments, R 51’ is C 3~8 In some embodiments, R 51’ is the unsubstituted C 3~6 In some embodiments, R 51’ is C 3~5 In some embodiments, R 51’ is selected from 3- to 6-membered heterocycles. 51’ is selected from unsubstituted 3-6 membered heterocycles. In some embodiments, q is selected from 1 to 6. In some embodiments, each D is independently selected from -O-. In some embodiments, z is selected from 1 to 10. In some embodiments, T is selected from hydrogen and C1-C6 alkyl. In some embodiments, optionally substituted C 1~30 Alkyl, optionally substituted C 3~8 R on carbocycles and optionally substituted 3- to 10-membered heterocycles 51’ The optional substituents in each occurrence are Halogen, -OR 30’ , -N(R 30’ )2, -(O-CH2-(CH2) p ) n -W, -SR 30’ , -C(O)R 30’ , -C(O)N(R 30’ )2, -N(R 30’ )C(O)R 30’ , -C(O)OR 30’ , -OC(O)R 30’ , -S(O)R 30’ , -S(O)2R 30’ , -P(O)(OR 30’ )2, -OP(O)(OR 30’ )2, -NO2, =O, =S, =N(R30’ ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30’ , -SR 30’ , -N(R 30’ )2, -C(O)R 30’ , -C(O)N(R 30’ )2, -N(R 30’ )C(O)R 30’ , -C(O)OR 30’ , -OC(O)R 30’ , -S(O)R 30’ , -S(O)2R 30’ , -P(O)(OR 30’ )2, -OP(O)(OR 30’ )2, -NO2, =O, =S, =N(R 30’ ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30’ , -SR 30’ , -N(R 30’ )2, -C(O)R 30’ , -C(O)N(R 30’ )2, -N(R 30’ )C(O)R 30’ , -C(O)OR 30’ , -OC(O)R 30’ , -S(O)R 30’ , -S(O)2R 30’ , -P(O)(OR 30’ )2, -OP(O)(OR 30’ )2, -NO2, =O, =S, =N(R 30’ ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 30’ , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from In some embodiments, R51’ R 30’ In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 carbocycle, and 3- to 10-membered heterocycle, optionally substituted with one or more substituents independently selected from:

[0141] In some embodiments of a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is -OH, and [ka] is selected from R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 4’ teeth, [ka] is selected from R 5 is selected from hydrogen, hydroxy, and optionally substituted C1-C6 alkoxy, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 6 and R 7 Let's get together and [ka] Forming R 22 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 Carbocycles, and -P(=O)(R 24 )2 is selected, R 100 teeth, Hydrogen and -(CH2-CH2-G) y -V, and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from is selected from R 110’ teeth, Hydrogen, -(CH2-CH2-G) y -V, -S(O)R 51’ , -S(O)2R 51’ , -C(O)R 51’ , -C(O)N(R51’ )2, and -C(O)OR 51’ , and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, -CN, C 3~20 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 20-membered heterocycle, and C 3~20 Carbocycles and 3- to 20-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 31 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from or R100 and R 110’ together with the nitrogen to which they are attached form a 3- to 10-membered heterocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy; R 1 is hydroxy, R 100 and R 110 is not an unsubstituted morpholine, Each G is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each D is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each y is selected from 3 to 20; Each z is selected from 1 to 20, each V is selected from hydrogen and optionally substituted —C1-C6 alkyl; each T is selected from hydrogen and optionally substituted —C1-C6 alkyl; Each R 31 is hydrogen, as well as C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 32 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 22 , R 51 The optional substituents on , V, and T, in each occurrence, are halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R 51’ is replaced as necessary in each occurrence of C3~8 Carbocycle, optionally substituted 3- to 10-membered heterocycle, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkoxy, C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 alkynyl), q is selected from 1 to 6; each p is selected from 1 or 2; each n is selected from 3 to 7; Each W is selected from hydrogen, —OH, —C1-C4 alkyl, and —O(C1-C4 alkyl).

[0142] In some embodiments of a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] is selected from R 22 is selected from optionally substituted C1-C6 alkyl; R 22 The above substituents, in each occurrence, are represented by -S(O)R 30 and -S(O)R 30 , preferably -S(O)R 30 are independently selected from R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy; R 4’ teeth, [ka] is selected from R 5 is selected from hydrogen, hydroxy, and optionally substituted C1-C6 alkoxy; R 6 and R 7 are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] and preferably R 6 and R 7 Let's get together and [ka] Forming R 100 is hydrogen and C 1~10 alkyl, R 110’ is -S(O)R 51’ and -S(O)R 51’ , preferably S(O)R 51’ is selected from R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8Carbocycle, optionally substituted 3- to 10-membered heterocycle, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl; R 51’ , and the substituents on T, in each occurrence, Halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 3~6 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 6-membered heterocycle; each D is independently selected from -O-; q is selected from 1 to 6; Each z is selected from 1 to 20, Each T is selected from hydrogen and optionally substituted -C1-C6 alkyl.

[0143] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), —OH and [ka] , R 22 is -(O-CH2-(CH2) p ) n -W and -OR 30 and R is a C1-C6 alkyl substituted with one or more substituents selected from 4’ teeth, [ka] Selected from R 100 is hydrogen and C 1~10 alkyl, R 110’ is -S(O)R 51’ and -S(O)R 51’ , preferably S(O)R 51’ is selected from.

[0144] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is -OH and [ka] is selected from.

[0145] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] and R 22 is optionally substituted C1-C6 alkyl, preferably optionally substituted C 2~4 In some embodiments, R22 is replaced as necessary 2~3 It is alkyl.

[0146] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] and R 22 is a substituted C1-C6 alkyl, preferably a substituted C 2~4 alkyl.

[0147] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 22 The above substituent is -OR 30 , -(O-CH2-(CH2) p ) n -W, -S(O)R 30 , -S(O)2R 30 , =O, =S, =N(R 30 ), and —CN.

[0148] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 22 The above optional substituents are -OR 30 , -S(O)2R 30 and ═O.

[0149] In some embodiments of the compounds or salts of formula (I), (IZ), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), -OR 30 and -S(O)R 30 R 30 is hydrogen and C 1~10 alkyl, 1~10Alkyl is a halogen, -OH, -CN, -NO2, -NH2, =O, =S, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 and optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 10-membered heterocycle.

[0150] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), -OR 30 and -S(O)R 30 R 30 In each occurrence, hydrogen and C 1~10 alkyl.

[0151] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] is selected from.

[0152] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] is selected from.

[0153] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4’ teeth, [ka] In some cases, [ka] R 100 is hydrogen and C 1~10 alkyl.

[0154] In some embodiments of a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), [ka] R 110’ is hydrogen, -S(O)R 51’ , and -S(O)R 51’ In some cases, [ka] R 110’ is -S(O)2R 51’ is selected from.

[0155] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8 Carbocycle, optionally substituted 3- to 10-membered heterocycle, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 alkyl.

[0156] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8 Carbocyclic ring, -((CH2) q -CH2-D) z-T and optionally substituted C 5~30 alkyl.

[0157] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8 Carbocyclic rings, and -((CH2) q -CH2-D) z -T.

[0158] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8 Carbocycle, optionally substituted 3- to 10-membered heterocycle, -((CH2) q -CH2-D) z -T and optionally substituted C 5~30 In some cases, z is 3 to 10. In some cases, z is 3 to 8. In some cases, z is 4 to 8. In some cases, z is 5 to 10.

[0159] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~6 In some cases, R is independently selected from carbocycle and optionally substituted 3- to 6-membered heterocycle. 51’ is, in each occurrence, a substitution C 1~4 Alkyl, C 3~6 are independently selected from carbocycles and 3- to 6-membered heterocycles.

[0160] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, saturated C 3~6 are independently selected from carbocycles and 5- to 6-membered saturated heterocycles.

[0161] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ is, in each occurrence, a substitution C 1~4 Alkyl and saturated C 3~6 carbocycles.

[0162] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ C 1~4 Alkyl is -OR 30 , C 3~10 It is substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle.

[0163] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ C 1~4 Alkyl is -OR 30 , and saturated C 3~6 and is substituted with one or more substituents selected from carbocycles.

[0164] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ C 1~4 Alkyl is -OR 30 , and -((CH2) q -CH2-D) z-T, z is 3 to 20, D is -O-, and T is selected from hydrogen and optionally substituted -C1-C6 alkyl.

[0165] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ C 1~4 Alkyl is -((CH2) q -CH2-D) z -T, where z is 1-20, D is -O-, and T is selected from hydrogen and optionally substituted -C1-C6 alkyl.

[0166] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ -((CH2) q -CH2-D) z In some cases, z is selected from 1 to 5. In some cases, z is selected from 3 to 5.

[0167] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ -OR 30 R 30 is hydrogen and C 1~10 alkyl, 1~10 Alkyl is a halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, and -OC 1~10 and optionally substituted with one or more substituents independently selected from alkyl.

[0168] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ -OR 30 R 30 is C 1~10 alkyl, 1~10 Alkyl is -OC 1~10 and optionally substituted with one or more substituents independently selected from alkyl.

[0169] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 51’ -OR 30 R 30 is C 1~3 alkyl, 1~10 Alkyl is -OC 1~3 and optionally substituted with one or more substituents independently selected from alkyl.

[0170] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] is selected from.

[0171] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] is selected from.

[0172] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] In some cases, R 4 teeth, [ka] is selected from.

[0173] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] is selected from.

[0174] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] is selected from.

[0175] In some embodiments of the compounds or salts of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 4 teeth, [ka] is selected from.

[0176] In some embodiments of a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 teeth, [ka] is selected from R 22is selected from optionally substituted C1-C6 alkyl; R 22 The above substituents, in each occurrence, are represented by -S(O)R 30 and -S(O)R 30 , preferably -S(O)R 30 are independently selected from R 30 In each occurrence, hydrogen and C 1~10 alkyl, 1~10 Alkyl is a halogen, -OH, -CN, -NO2, -NH2, =O, =S, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 and optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 10-membered heterocycle.

[0177] In some embodiments of a compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), R 1 is -OH and [ka] is selected from R 2 is selected from optionally substituted C1-C6 alkoxy, preferably —OCH3; R 3 is selected from optionally substituted C1-C6 alkoxy, preferably —OCH3; R 4’ teeth, [ka] is selected from R 5 is selected from hydroxy and optionally substituted C1-C6 alkoxy, preferably —OH; R 6 and R 7are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] , preferably [ka] Forming R 22 is selected from optionally substituted C1-C6 alkyl; R 100 is hydrogen and C 1~10 alkyl, R 110’ is hydrogen and -S(O)R 51’ , preferably -S(O)R 51’ is selected from R 22 , R 51’ and the optional substituents on T, in each occurrence, Halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -NO2, =O, =S, -S(O)2R 30 , and -CN, and C 3~10 Carbocycles and 3- to 6-membered heterocycles (each of which is substituted with halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Alkyl, -OC 1~6 and optionally substituted with one or more substituents independently selected from alkyl, are independently selected from R 30 In each occurrence, hydrogen, C 1~10 Alkyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10Haloalkyl, and -OC 1~10 optionally substituted with one or more substituents independently selected from alkyl; R 51’ is, in each occurrence, a substitution C 1~4 Alkyl, optionally substituted C 3~8 Carbocyclic rings, and -((CH2) q -CH2-D) z - are independently selected from T, each D is independently selected from -O-; each T is selected from hydrogen and optionally substituted —C1-C6 alkyl; z is selected from 1 to 10; q is selected from 1 to 6; each p is selected from 1 or 2; each n is selected from 3 to 7; Each W is selected from hydrogen, —OH, —C1-C4 alkyl, and —O(C1-C4 alkyl).

[0178] In some embodiments, the compound or salt of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG) is [ka] [ka] [ka] is selected from. Compound group 2

[0179] In a second aspect, the present disclosure provides a compound represented by the structure of formula X: [ka] or a pharmaceutically acceptable salt thereof, wherein: L is an optionally substituted C 1~8 alkylene; R 1 is a carboxylic acid or a carboxylic acid isostere, R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy groups, 3- to 10-membered heterocycles, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 4 teeth, [ka] and an optionally substituted 3- to 10-membered heterocycle, and L is selected from optionally substituted C 3~8 When R is alkylene, 4 is further selected from methoxy, -LR 1 is ethyl acetate, tert-butyl acetate, benzyl acetate, or methyl 2-phenylacetate, R 4 is not methoxy, R 4wherein the optionally substituted heterocycle is optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, ═O, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; z is 0, 1, 2, 3, 4 or 5; R 5 is selected from hydrogen, hydroxy, and an optionally substituted C1-C6 alkoxy group, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, a C1-C6 alkoxy group, a 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 6 and R 7 are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] Forming R 25 is, in each occurrence, hydrogen, optionally substituted C1-C6 alkyl, -D-(CH2-CH2-G) y -V, C substituted as needed 3~20 independently selected from a carbocycle and an optionally substituted 3- to 20-membered heterocycle; R 25 is optionally substituted C1-C6 alkyl, the substituents on the C1-C6 alkyl, at each occurrence, are halogen, —OH, —CN, —NO2, —NH2, ═O, ═S, —C(O)N(R 31)2, -OC(O)N(R 31 )2, -C(O)OR 31 , -P(O)(R 31 )2, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, -OC 1~10 Alkyl-CN, -OC 1~10 Alkyl-C(O)OR 31 , C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~20 independently selected from a carbocycle, and a 3- to 20-membered heterocycle; R 25 C, where necessary, is replaced 3~20 When the ring is a carbocyclic ring or an optionally substituted 3- to 20-membered heterocyclic ring, C 3~20 Substituents on the carbocycle and 3- to 20-membered heterocycle, at each occurrence, are halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, and C 2~6 alkynyl; D is selected from a bond or —O—; Each G is -O-, -NR 32 independently selected from -, -S-, or -SO2-; Each y is selected from 1 to 20, each V is selected from hydrogen and optionally substituted —C1-C6 alkyl; R 30In each occurrence, hydrogen, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is selected from the group consisting of halogen, -OH, -OSi(C1-C6 alkyl), -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R' and R'' in each occurrence are hydrogen, halogen, -OR 31 , and halogens and -OR 31 C optionally substituted with one or more substituents independently selected from 1~8 alkyl; R 31 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 Carbocycles and 3- to 12-membered heterocycles (each of which is selected from the group consisting of halogen, -OH, -OSi(C1-C6 alkyl), -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, -OC 1~10 Alkyl-OH, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 12-membered heterocycle; R 32 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C3~10 Carbocycles and 3- to 10-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; The substituents on V and L, in each occurrence, are Halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from

[0180] In certain embodiments, the compound of formula (X) has the formula (XA): [ka] or a salt thereof.

[0181] In certain embodiments, the compound of formula (X) has the formula (XB): [ka] or a salt thereof.

[0182] In certain embodiments, the compound of formula (X) has the formula (XC): [ka] or a salt thereof.

[0183] In certain embodiments, the compound of formula (X) has the formula (XD): [ka] or a salt thereof.

[0184] In certain embodiments, the compound of formula (X) has the formula (XE): [ka] or a salt thereof.

[0185] In certain embodiments, the compound of formula (X) has the formula (XF): [ka] or a salt thereof.

[0186] In certain embodiments, the compound of formula (X) has the formula (XG): [ka] or a salt thereof.

[0187] In certain embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 is a carboxylic acid isostere. The carboxylic acid functional group is an important component of the pharmacophore. However, the presence of this moiety can also cause significant drawbacks, including metabolic instability, toxicity, and limited passive diffusion across biological membranes. To avoid these potential drawbacks while retaining the desirable properties of the carboxylic acid moiety, R 1 may be selected from carboxylic acid isosteres, which are chemical moieties that exhibit similar or improved physical and biological properties compared to carboxylic acid groups.

[0188] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 is selected from esters, hydroxamic acids, hydroxamic acid esters, phosphonic acids, phosphinic acids, sulfonic acids, sulfinic acids, sulfones, sulfonamides, acylsulfonamides, sulfonylureas, acylureas, tetrazoles, thiazolidinediones, oxazolidinediones, oxadiazol-5(4H)-ones, thiadiazole-5(4H)-thiones, oxathiadiazole-2-oxides, oxadiazole-5(4H)-thiones, isoxazoles, tetramic acids, cyclopentane 1,3-dione, cyclopentane 1,2-dione, squaric acids, and substituted phenols.

[0189] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 is selected from hydroxamic acids, hydroxamic acid esters, phosphonic acids, phosphinic acids, sulfonic acids, sulfinic acids, sulfones, sulfonamides, acylsulfonamides, sulfonylureas, acylureas, tetrazoles, thiazolidinediones, oxazolidinediones, oxadiazol-5(4H)-ones, thiadiazol-5(4H)-thiones, oxathiadiazole-2-oxides, oxadiazole-5(4H)-thiones, isoxazoles, tetramic acids, cyclopentane 1,3-dione, cyclopentane 1,2-dione, squaric acids, and substituted phenols.

[0190] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1is selected from esters, carboxylic acids, hydroxamic acids, hydroxamic acid esters, phosphonic acids, phosphinic acids, sulfonic acids, sulfinic acids, sulfones, sulfonamides, acylsulfonamides, sulfonylureas, acylureas, tetrazoles, thiazolidinediones, oxazolidinediones, oxadiazol-5(4H)-ones, thiadiazole-5(4H)-thiones, oxathiadiazole-2-oxides, oxadiazole-5(4H)-thiones, isoxazoles, tetramic acids, cyclopentane 1,3-dione, cyclopentane 1,2-dione, squaric acids, and substituted phenols.

[0191] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is selected from carboxylic acids, hydroxamic acids, hydroxamic acid esters, phosphonic acids, phosphinic acids, sulfonic acids, sulfinic acids, sulfonamides, sulfones, acylsulfonamides, sulfonylureas, acylureas, tetrazoles, thiazolidinediones, oxazolidinediones, oxadiazol-5(4H)-ones, thiadiazole-5(4H)-thiones, oxathiadiazole-2-oxides, oxadiazole-5(4H)-thiones, isoxazoles, tetramic acids, cyclopentane 1,3-dione, cyclopentane 1,2-dione, squaric acids, and substituted phenols.

[0192] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1is selected from carboxylic acid, hydroxamic acid, hydroxamic acid ester, phosphonic acid, phosphinic acid, sulfonic acid, sulfinic acid, sulfonamide, sulfone, acylsulfonamide, sulfonylurea, acylurea, tetrazole, thiazolidinedione, oxazolidinedione, oxadiazol-5(4H)-one, thiadiazole-5(4H)-thione, oxathiadiazole-2-oxide, oxadiazole-5(4H)-thione, isoxazole, tetramic acid, cyclopentane 1,3-dione, cyclopentane 1,2-dione, squaric acid, and substituted phenols; 4 is not methoxy.

[0193] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is selected from ester, carboxylic acid, hydroxamic acid, hydroxamic acid ester, phosphonic acid, phosphinic acid, sulfonic acid, sulfinic acid, sulfonamide, sulfone, acylsulfonamide, sulfonylurea, acylurea, tetrazole, thiazolidinedione, oxazolidinedione, oxadiazol-5(4H)-one, thiadiazole-5(4H)-thione, oxathiadiazole-2-oxide, oxadiazole-5(4H)-thione, isoxazole, tetramic acid, cyclopentane 1,3-dione, cyclopentane 1,2-dione, squaric acid, and substituted phenols; 4 is not methoxy.

[0194] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a carboxylic acid. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR1 but, [ka] If R is represented by 4 is not methoxy. In some embodiments, -LR 1 but, [ka] In some embodiments, L is unsubstituted. 1 but, [ka] where L is C 3~8 When selected from alkylene, L is unsubstituted. In some embodiments, -LR 1 but, [ka] where L is C 1~2 When selected from alkylene, L is substituted.

[0195] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is an ester. In some embodiments, -LR 1 teeth, [ka] In some embodiments, R 41 is C 1~6 In some embodiments, R is selected from alkyl and benzyl. 41 is C 1~6 In some embodiments, R 41 is C 1~4 In some embodiments, R 41 is methyl. In some embodiments, R 41is ethyl. In some embodiments, R 41 is selected from isopropyl and t-butyl. 41 is isopropyl. In some embodiments, R 41 is n-propyl. In some embodiments, R 41 is t-butyl. In some embodiments, R 41 is n-butyl. In some embodiments, R 41 is benzyl. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 but, [ka] When L is represented by C 2~8 In some embodiments, -LR is selected from alkylene. 1 but, [ka] and when L is C alkylene, R 4 is not methoxy. In some embodiments, -LR 1 teeth, [ka] and R 4 is not methoxy. In some embodiments, -LR 1is ethyl acetate, tert-butyl acetate, benzyl acetate, or methyl 2-phenylacetate, R 4 is not methoxy. In some embodiments, -LR 1 but, [ka] R when selected from 4 is not methoxy. In some embodiments, -LR 1 but, [ka] If R 4 is not methoxy. In some embodiments, -LR 1 but, [ka] If R 4 is not methoxy. In some embodiments, -LR 1 but, [ka] If R 4 is not methoxy. In some embodiments, -LR 1 but, [ka] If R 4 is not methoxy.

[0196] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a hydroxamic acid ester. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0197] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is selected from hydroxamic acid, phosphonic acid, phosphinic acid, sulfonic acid, sulfinic acid, sulfonamide, sulfone, acylsulfonamide, sulfonylurea, acylurea, tetrazole, thiazolidinedione, oxazolidinedione, oxadiazol-5(4H)-one, thiadiazole-5(4H)-thione, oxathiadiazole-2-oxide, oxadiazole-5(4H)-thione, isoxazole, tetramic acid, cyclopentane 1,3-dione, cyclopentane 1,2-dione, squaric acid, and substituted phenols.

[0198] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a hydroxamic acid. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0199] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is phosphate. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0200] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a phosphonic acid. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0201] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a sulfonic acid. In some embodiments, -LR 1 teeth, [ka] In some embodiments, R 1 The carboxylic acid isostere of may be a salt, e.g., -LR 1 teeth, [ka] is expressed by

[0202] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a sulfinic acid. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0203] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a sulfonamide. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0204] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a sulfone. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0205] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is an acylsulfonamide. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0206] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a sulfonylurea. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0207] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is an acylurea. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0208] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is tetrazole. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0209] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a thiazolidinedione. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0210] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is an oxazolidinedione. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0211] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is oxadiazol-5(4H)-one. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0212] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is thiadiazole-5(4H)-thione. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0213] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is oxathiadiazole-2-oxide. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0214] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is oxadiazole-5(4H)-thione. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0215] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is isoxazole. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0216] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a tetramic acid. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0217] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is cyclopentane 1,3-dione. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0218] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR1 R 1 is cyclopentane 1,2-dione. In some embodiments, -LR 1 teeth, [ka] is expressed by

[0219] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is squaric acid. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0220] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 R 1 is a substituted phenol. In some embodiments, -LR1 The substituted phenol of formula (I) is optionally substituted with one or more substituents independently selected from halogen, -S-, -S(O)-, and -S(O)-. In some embodiments, -LR- 1 teeth, [ka] is expressed by

[0221] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 The substituted phenol of formula (I) is substituted with one or more substituents selected from halogen. In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0222] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 teeth, [ka] In some embodiments, -LR 1 teeth, [ka] In some embodiments, -LR 1teeth, [ka] In some embodiments, -LR 1 teeth, [ka] is expressed by

[0223] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 teeth, [ka] is expressed by

[0224] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 teeth, [ka] is expressed by

[0225] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), -LR 1 teeth, [ka] is expressed by

[0226] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted C 1~8 In some embodiments, optionally substituted C alkylene. 1~8Alkylene is selected from methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, and octylene. In some embodiments of the compounds or salts of Formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted C 1~2 When R is alkylene, 4 In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is not methoxy. 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -NO2, =O, C 1~10 Alkyl, C 1~10 In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted with one or more substituents independently selected from halogen, -OR, -CH ... 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -NO2, C 1~10 Alkyl, C 1~10In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted with one or more substituents independently selected from halogen, -OR, -CH ... 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -NO2, C 1~10 Alkyl, C 1~10 and optionally substituted with one or more substituents independently selected from haloalkyl, and -CN. In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is unsubstituted, e.g., L is methylene, ethylene, or propylene.

[0227] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted C 1~8 alkylene, and L is —(O—CH—(CH) p ) n and optionally substituted with one or more substituents independently selected from -W, where each p is selected from 1 or 2, each n is selected from 3 to 7, and each W is selected from hydrogen, -OH, -C1-C4 alkyl, and -O(C1-C4 alkyl).

[0228] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted C 3~8 When R is alkylene, 4is further selected from methoxy.

[0229] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is selected from the group consisting of propylene, butylene, pentylene, hexylene, heptylene, and octylene, any one of which is selected from the group consisting of halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -NO2, =O, C 1~10 Alkyl, C 1~10 optionally substituted with one or more substituents independently selected from haloalkyl, -CN, and -CN; 3~8 In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -NO2, C 1~10 Alkyl, C 1~10 and optionally substituted with one or more substituents independently selected from haloalkyl, and -CN.

[0230] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is a substituted C 1~8 In some embodiments, the substituted C 1~8 Alkylene is selected from methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, and octylene.

[0231] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is substituted C 3~8 When R is alkylene, 4 is further selected from methoxy.

[0232] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is a halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -NO2, C 1~10 Alkyl, C 1~10 C substituted with one or more substituents independently selected from haloalkyl, and —CN 3~8 It is alkylene.

[0233] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is a halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -NO2, =O, C 1~10 Alkyl, C 1~10 C substituted with one or more substituents independently selected from haloalkyl, and —CN 3~8 It is alkylene.

[0234] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents at each occurrence being independently selected from hydroxy, halogen, —CN, —NO2, and C1-C6 alkoxy. 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents at each occurrence being independently selected from hydroxy, halogen, —NO2, and C1-C6 alkoxy.

[0235] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 2 is selected from hydrogen and C1-C6 alkoxy. 2 is selected from hydrogen and -OMe. 2 is -OMe.

[0236] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents at each occurrence being independently selected from hydroxy and C1-C6 alkoxy. 3is selected from hydrogen and C1-C6 alkoxy.

[0237] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 3 is selected from C1-C6 alkoxy. 3 is -OMe.

[0238] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 5 is selected from hydrogen, hydroxy, and an optionally substituted C1-C6 alkoxy group, the substituents at each occurrence being independently selected from hydroxy, halogen, —CN, —NO2, and C1-C6 alkoxy.

[0239] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 5 is hydroxy.

[0240] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 6 and R 7 are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy. In some instances, R 6 and R 7 are each independently selected from hydrogen and hydroxy. 6 and R 7 are each hydrogen. 6 is hydrogen and R 7 is C1-C6 alkoxy. In some embodiments, R 6 is hydrogen and R 7 In some embodiments, R 6 and R 7Let's get together and [ka] Form.

[0241] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] and optionally substituted 3- to 10-membered heterocycles.

[0242] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] In some embodiments, z is 0, 1, 2, 3, 4, or 5. In some embodiments, z is 1, 2, 3, 4, or 5. In some embodiments, z is 1, 2, or 3. In some embodiments, z is 2, 3, or 4. In some embodiments, when z is 0, R 25 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 In some embodiments, when z is 1, R 25 is an optionally substituted C1-C6 alkyl, an optionally substituted 3-10 membered heterocycle, and an optionally substituted C 3~10 Carbocycles are selected from:

[0243] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] Each R' and R'' is hydrogen, -OR 31 , and one or more -OR 31 C, substituted as needed 1~3 In some embodiments, R' and R" are independently selected from alkyl. In some embodiments, R' and R" are the same substituent, e.g., R' is methyl and R" is methyl, or R' is hydrogen and R" is hydrogen. In some embodiments, each R' and R" is independently selected from different substituents, e.g., R' is methyl and R" is ethyl. In some embodiments, each R' and R" is selected from hydrogen and one or more -OR 31 C, substituted as needed 1~3 In some embodiments, R′ and R″ are each independently selected from one or more —OR alkyl. 31 C, substituted as needed 1~3 In some embodiments, R' and R'' are each hydrogen.

[0244] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is hydrogen, optionally substituted C1-C6 alkyl, -D-(CH2-CH2-G) y -V, an optionally substituted 3- to 10-membered heterocycle, and an optionally substituted C 3~10 Carbocycles are selected from:

[0245] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is hydrogen. In some embodiments, R4 teeth, [ka] is.

[0246] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is optionally substituted C1-C6 alkyl. In some embodiments, R 25 Optionally substituted C1-C6 alkyl is -OH and -OC 1~6 In some embodiments, R is substituted with one or more substituents selected from alkyl. 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0247] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -P(O)(R 31 )2. In some embodiments, —P(O)(R 31 )2R 31 -OH and -OC 1~6 C substituted with one or more substituents selected from alkyl 1~6 In some embodiments, R 4 teeth, [ka] is expressed by

[0248] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2-G) y In some embodiments, D is -V. In some embodiments, D is a bond. In some embodiments, D is -O-. In some embodiments, -D-(CH2-CH2-G) y In -V, y is 1 to 1000. In some embodiments, y is 1 to 800. In some embodiments, y is 1 to 500. In some embodiments, y is 1 to 300. In some embodiments, y is 1 to 100. In some embodiments, y is 1 to 50. In some embodiments, y is 1 to 25, for example, 1 to 10 or 1 to 8. In some embodiments, y is 3 to 1000. In some embodiments, y is 10 to 1000. In some embodiments, y is 50 to 1000. In some embodiments, y is 100 to 1000. In some embodiments, y is 200 to 1000. In some embodiments, y is 500 to 1000. In some embodiments, R 25 -D-(CH2-CH2-G) y -V, y is 3 to 10. In some embodiments, R 25 -D-(CH2-CH2-G) y In -V, y is 5 to 10. In some embodiments, y is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100. In some embodiments, y is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100.

[0249] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2-G) y -V, -D-(CH2-CH2-G) y In some embodiments, G in -V is -O- in each occurrence. 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is selected from.

[0250] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2-G) y In some embodiments, D is selected from a bond or -O-. In some embodiments, D is a bond. In some embodiments, D is -O-. In some embodiments, when z is 0, D is a bond. In some embodiments, when z is 1, D is a bond. In some embodiments, when z is 2, D is a bond. In some embodiments, when D is -O-, z is selected from 1, 2, 3, 4, or 5. In some embodiments, when D is -O-, z is selected from 2, 3, 4, or 5.

[0251] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2) y -V, -D-(CH2-CH2-G) y -V G in each occurrence is -NR 32 In some embodiments, -NR 32 -Each R 32 is hydrogen, and C 1~10 Alkyl (each of which is a halogen, -OH, C 1~10 Alkyl, -C 1~10 Haloalkyl, and -OC 1~10 and optionally substituted with one or more substituents independently selected from alkyl.

[0252] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2-G) y In some embodiments, the C1-C6 alkyl of V is represented by -V, where V is an optionally substituted C1-C6 alkyl. In some embodiments, the C1-C6 alkyl of V is -(O-CH2-(CH2) p ) n and optionally substituted with one or more substituents independently selected from -W, where each p is selected from 1 or 2, each n is selected from 3 to 7, and each W is selected from hydrogen, -OH, -C1-C4 alkyl, and -O(C1-C4 alkyl).

[0253] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2-G) y In some embodiments, the C1-C6 alkyl of V is selected from the group consisting of halogen, -OR 30 , -N(R 30 )2, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and —CN.

[0254] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2-G) y In some embodiments, the C1-C6 alkyl of V is selected from the group consisting of halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR 30 , -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and —CN.

[0255] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is -D-(CH2-CH2-G) y -V, where V is -OR 30 and -N(R 30 In some embodiments, V is a substituted C1-C6 alkyl having one or more substituents independently selected from: -OR 30 and R is a substituted C1-C6 alkyl having one or more substituents independently selected from 30 is hydrogen, as well as C 1~5 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, and -OC 1~10 optionally substituted with one or more substituents independently selected from alkyl.

[0256] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25is an optionally substituted 3-6 membered heterocyclic ring. In some embodiments, the 3-6 membered heterocyclic ring is saturated. In some embodiments, the 3-6 membered heterocyclic ring is unsaturated. In some embodiments, the optionally substituted 3-6 membered heterocyclic ring contains at least one heteroatom selected from nitrogen, oxygen, sulfur, and any combination thereof. In some embodiments, the optionally substituted 3-6 membered heterocyclic ring contains at least one heteroatom selected from N and O, and the 3-6 membered heterocyclic ring is C 1~6 In some embodiments, R 4 teeth, [ka] is selected from.

[0257] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka] R 25 is replaced as necessary 3~10 In some embodiments, R 25 is replaced as necessary 3~6 In some embodiments, C 3~6 The carbocyclic ring is saturated. 3~6 The carbocyclic ring is unsaturated. In some embodiments, R 4 teeth, [ka] is selected from.

[0258] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is.

[0259] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0260] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0261] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0262] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0263] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 is hydroxy, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] isn't it.

[0264] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0265] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0266] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0267] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted C 1~6 alkylene; R 1 is a sulfone, R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy; R 4 teeth, [ka] and optionally substituted 3- to 10-membered heterocycles, preferably [ka] is selected from R 4 wherein the optionally substituted heterocycle is optionally substituted with one or more substituents selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, ═O, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; z is 0, 1, 2, 3, 4 or 5; R 5 is selected from hydrogen, hydroxy, and an optionally substituted C1-C6 alkoxy group; R 6 and R 7 are each independently selected from hydrogen, hydroxy, and C1-C6 alkoxy, or R 6 and R 7 Let's get together and [ka] and preferably R 6 and R 7 Let's get together and [ka] Form.

[0268] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), L is optionally substituted C 1~5 alkylene.

[0269] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 is selected from carboxylic acids, esters, sulfones, and sulfonic acids.

[0270] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), the ester is —C(O)(C 1~6 alkyl), and the C 1~6 Alkyl is a halogen, -OH, -NO2, =O, -OC 1~6 alkyl, and sulfone is —S(O)C 1~6 alkyl, 1~6 Alkyl is a halogen, -OH, -NO2, =O, -OC 1~6 and optionally substituted with one or more substituents selected from alkyl.

[0271] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 teeth, [ka] is selected from.

[0272] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 is selected from sulfone and sulfonic acid. 1 teeth, [ka] In some cases, R 1 teeth, [ka] is selected from.

[0273] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 teeth, [ka] is selected from.

[0274] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 1 is selected from sulfones and esters. In some cases, R 1 teeth, [ka] is selected from.

[0275] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] and R' and R'' in each occurrence are hydrogen, hydroxy, and -OR 31 are independently selected from R 31 is C 1~10 In some cases, z is selected from 1, 2, and 3.

[0276] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 25 is hydrogen, and -D-(CH2-CH2-G) y -V, D is -O-, G is -O-, y is 1 to 3, and V is selected from -C1 to C6 alkyl and hydrogen.

[0277] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 is methoxy.

[0278] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0279] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0280] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0281] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0282] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] In some cases, R 4 teeth, [ka] is selected from.

[0283] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka]

[0284] In some embodiments of a compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), [ka]

[0285] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] [ka] is selected from.

[0286] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0287] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0288] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0289] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] [ka] is selected from.

[0290] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0291] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] [ka] is selected from.

[0292] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0293] In some embodiments of the compound or salt of formula (X), (XA), (XB), (XC), (XD), (XE), (XF), or (XG), R 4 teeth, [ka] is selected from.

[0294] In some embodiments, the compound or salt of formula (I) is [ka] [ka] is selected from. Compound group 3

[0295] In a third aspect, the present disclosure provides a compound represented by the structure of formula (L): [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 teeth, [ka] , 3- to 10-membered heterocycles, and C 3~10 carbocycle, and the 3- to 10-membered heterocycle and C 3~10 The carbocyclic rings are each represented by R 33 and optionally substituted with one or more substituents independently selected from R 2is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 3 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, C1-C6 alkoxy groups, 3- to 10-membered heterocycles, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 4 teeth, [ka] and R 5 is selected from hydrogen, hydroxy, and an optionally substituted C1-C6 alkoxy group, the substituents, at each occurrence, being selected from hydroxy, halogen, —CN, —NO2, a C1-C6 alkoxy group, a 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl; R 6 and R 7 are hydrogen, hydroxy, and C, respectively. 1~6 alkoxy, or R 6 and R 7 Let's get together and [ka] Forming R 20 is selected from hydrogen and optionally substituted C1-C6 alkyl; R 21 is selected from optionally substituted C1-C6 alkyl and optionally substituted 3- to 7-membered heterocycle; R 22 is hydrogen, optionally substituted C1-C6 alkyl, -Si(R 24 )3, and -P(=O)(R 24 )2 is selected, R 23 is selected from optionally substituted C1-C6 alkyl and optionally substituted 3- to 7-membered heterocycle; R 24 is an optionally substituted C1-C6 alkyl; R 20 , R 21 , R 22 , R 23 , and R 24 The above substituents, in each occurrence, Halogen, -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -SR 30 , -N(R 30 )2, -C(O)R 30, -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 30 , -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -P(O)(OR 30 )2, -OP(O)(OR30 )2, -NO2, =O, =S, =N(R 30 ), -CN, C 1~6 Alkyl, C 1~6 Alkyl-R 30 , C 2~6 Alkenyl, and C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from each p is selected from 1 or 2; each n is selected from 3 to 7; each W is selected from hydrogen, —OH, —C1-C4 alkyl, and —O(C1-C4 alkyl); R 30 In each occurrence, Hydrogen, and C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 Carbocycles and 3- to 12-membered heterocycles (each of which is selected from the group consisting of halogen, -OH, -OSi(C1-C6 alkyl), -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 optionally substituted with one or more substituents independently selected from carbocycle, 3- to 12-membered heterocycle, and haloalkyl are independently selected from z is selected from 0 to 2; R' and R'' are hydrogen, halogen, -OR 31 , and halogens and -OR 31 C optionally substituted with one or more substituents independently selected from 1~3 alkyl; Ring A is selected from optionally substituted C3-C5 carbocycles and optionally substituted 3-5 membered heterocycles, and the substituents on Ring A, at each occurrence, are Halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), and -CN, C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl (each of which is halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle, and C 3~10 Carbocycles and 3- to 10-membered heterocycles, each of which may contain halogen, -OR 31 , -SR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31, -S(O)R 31 , -S(O)2R 31 , -P(O)(OR 31 )2, -OP(O)(OR 31 )2, -NO2, =O, =S, =N(R 31 ), -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 alkynyl, optionally substituted with one or more substituents independently selected from are independently selected from R 31 represents hydrogen, and C in each occurrence. 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 Carbocycles and 3- to 12-membered heterocycles (each of which is substituted with halogen, -OH, -CN, -NO2, -NH2, =O, =S, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~12 optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 12-membered heterocycle; R 33 is, in each occurrence, selected from hydroxy, halogen, -CN, -NO2, ═O, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, 3- to 10-membered heterocycle, and C 3~10 carbocycle, wherein the 3- to 10-membered heterocycle and C 3~10 Each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, and C1-C6 alkoxyC1-C6 alkyl.

[0296] In certain embodiments, the compound of formula (L) has the formula (LA) [ka] or a salt thereof.

[0297] In certain embodiments, the compound of formula (L) has the formula (LB): [ka] or a salt thereof.

[0298] In certain embodiments, the compound of formula (L) has the formula (LC): [ka] or a salt thereof.

[0299] In certain embodiments, the compound of formula (L) has the formula (LD) [ka] or a salt thereof.

[0300] In certain embodiments, the compound of formula (L) has the formula (LE) [ka] or a salt thereof.

[0301] In certain embodiments, the compound of formula (L) has the formula (LF) [ka] or a salt thereof.

[0302] In certain embodiments, the compound of formula (L) has the formula (LG): [ka] or a salt thereof.

[0303] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 In some embodiments, z is selected from 0, 1, or 2. In some embodiments, z is selected from 0 and 1. In some embodiments, z is selected from 0 and 2. In some embodiments, z is selected from 1 and 2. In some embodiments, z is selected from optionally substituted -CH- and optionally substituted -CHCH-.

[0304] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), z is 0 and R 4 teeth, [ka] is expressed by

[0305] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), z is 1 and R 4 teeth, [ka] is expressed by

[0306] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), z is 2 and R 4 teeth, [ka] is expressed by

[0307] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), [ka] Each R' and R'' is hydrogen, halogen, -OR 31 , and halogens and -OR 31 C optionally substituted with one or more substituents independently selected from 1~3 In some embodiments, z is 1 and R' and R" are independently selected from alkyl. In some embodiments, z is 1 and R' and R" are the same substituent, e.g., R' is methyl and R" is methyl, or R' is hydrogen and R" is hydrogen. In some embodiments, z is 1 and R' and R" are independently selected from different substituents, e.g., R' is methyl and R" is ethyl. In some embodiments, each R' and R" is selected from hydrogen and C 1~3 In some embodiments, each R' and R'' is independently selected from hydrogen, halogen, and -OR 31 In some embodiments, z is 1 and R′ and R″ are each hydrogen.

[0308] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from an optionally substituted C3-C5 carbocycle, e.g., an optionally substituted C3-C4 carbocycle, an optionally substituted C3 carbocycle, an optionally substituted C4 carbocycle, or an optionally substituted C5 carbocycle. In some embodiments, the optionally substituted carbocycle is unsaturated. In some embodiments, the optionally substituted carbocycle is saturated.

[0309] In some embodiments of the compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 3- to 5-membered heterocycle, such as an optionally substituted 3- to 4-membered heterocycle, an optionally substituted 3-membered heterocycle, an optionally substituted 4-membered heterocycle, or an optionally substituted 5-membered heterocycle. In some embodiments, the optionally substituted heterocycle is unsaturated. In some embodiments, the optionally substituted heterocycle is saturated.

[0310] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from an optionally substituted C3-C5 carbocycle and an optionally substituted 3-5 membered heterocycle, each substituent being selected from halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, and -CN; and halogens, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, -N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, -CN, C 3~6 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 6-membered heterocycles 1~3 alkyl.

[0311] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from an optionally substituted C3-C5 carbocycle and an optionally substituted 3-5 membered heterocycle, and one or more substituents are one or more -OR 31 C optionally substituted with substituents 1~3 alkyl.

[0312] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is [ka] and optionally substituted C3-C5 carbocycles selected from the group consisting of: 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and halogens, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~6 C optionally substituted with one or more substituents independently selected from carbocycles and 3- to 6-membered heterocycles 1~6 and optionally substituted with one or more substituents independently selected from alkyl.

[0313] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] and z is selected from 1 and 2. In some embodiments, z is selected from 0, 1, and 2. In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] and z is selected from 0, 1, and 2. In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] and z is selected from 0, 1, and 2. In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0314] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the C3-carbocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31)2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0315] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the C3-carbocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle.

[0316] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the C4-carbocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0317] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the C4-carbocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10and optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle.

[0318] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the C5-carbocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0319] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the C5-carbocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle.

[0320] In some embodiments of the compounds or salts of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 3-5 membered heterocycle, wherein one or more of the substituents is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 In some embodiments, the optionally substituted 3- to 5-membered heterocyclic ring is saturated. In some embodiments, the optionally substituted 3- to 5-membered heterocyclic ring is unsaturated.

[0321] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the 3- to 5-membered heterocyclic ring contains at least one heteroatom selected from oxygen, nitrogen, sulfur, boron, phosphorus, silicon, selenium, and any combination thereof. In some embodiments, the 3- to 5-membered heterocyclic ring contains at least one heteroatom selected from oxygen, nitrogen, and sulfur.

[0322] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is a three-membered heterocycle, and the heterocycle contains one heteroatom selected from oxygen, nitrogen, and sulfur. In some embodiments, ring A is selected from halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and a 3-membered heterocycle optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle.

[0323] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and a 4-membered heterocycle optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle.

[0324] In some embodiments of the compounds or salts of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 4-membered heterocycle containing one oxygen atom, wherein the 4-membered heterocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO, =O, =S, and -CN. In some embodiments, -OR 31 R 31 In each occurrence, C 1~6In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0325] In some embodiments of the compounds or salts of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is a 4-membered substituted heterocycle containing one oxygen atom, and the 4-membered heterocycle is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO, =O, =S, and -CN). In some embodiments, -OR 31 R 31 In each occurrence, C 1~10 In some embodiments, R 4 teeth, [ka] is selected from.

[0326] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the optionally substituted 4-membered heterocycle contains 1 or 2 heteroatoms selected from nitrogen and sulfur.

[0327] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 4-membered heterocycle containing one or two nitrogen atoms. In some embodiments, the optionally substituted 4-membered heterocycle is selected from azetidine, 2,3-dihyroazete, azate, 1,3-diazetidine, and 1,4-diazetidine. One of them is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle. In some embodiments, -OR 31 R 31 In each occurrence, C 1~10 is independently selected from alkyl and hydrogen.

[0328] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 4-membered heterocycle selected from azetidine, 1,3-diazetidine, and 1,4-diazetidine, any one of which is selected from halogen, —OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle. In some embodiments, -OR 31 R 31 In each occurrence, C 1~10 is independently selected from alkyl and hydrogen.

[0329] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 4-membered heterocycle selected from 2,3-dihydroazate and azate, any one of which may be selected from halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle. In some embodiments, -OR 31 R 31 In each occurrence, C 1~10 is independently selected from alkyl and hydrogen.

[0330] In some embodiments of the compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is C 1~10 alkyl (each of which is -OR 31 In some embodiments, the azetidine is optionally substituted with one or more substituents independently selected from: 31 R 31 In each occurrence, C 1~10In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0331] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocyclic ring containing at least one heteroatom selected from nitrogen, oxygen, sulfur, and any combination thereof. In some embodiments, ring A is an optionally substituted 5-membered heterocyclic ring containing four heteroatoms selected from nitrogen, oxygen, sulfur, and any combination thereof.

[0332] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing 4 nitrogen atoms. In some embodiments, ring A is selected from the group consisting of halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 and optionally substituted with one or more substituents independently selected from a carbocycle and a 3- to 10-membered heterocycle.

[0333] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing three heteroatoms selected from nitrogen, oxygen, sulfur, and any combination thereof.

[0334] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing three heteroatoms selected from nitrogen, oxygen, and sulfur, and the optionally substituted 5-membered heterocycle is selected from 1,2,4-triazole, 1,2,3-triazole, 1,2,5-oxadiazole, 1,2,3-oxadiazole, 1,3,4-thiadiazole, and 1,2,5-thiadiazole, any one of which is selected from halogen, —OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0335] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing two heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the optionally substituted 5-membered heterocycle is selected from pyrazolidine, imidazolidine, 2-pyrazoline, 2-imidazoline, pyrazole, imidazole, 1,3-dioxolane, oxazole, isoxazole, thiazole, isothiazole, 1,2-oxathiolane, and 1,3-oxathiolane, any one of which is selected from halogen, -OR31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0336] In some embodiments of the compounds or salts of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is a 5-membered substituted heterocycle containing two oxygen atoms, and the optionally substituted 5-membered heterocycle is selected from the group consisting of, in each occurrence, a halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 2~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle.

[0337] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 is hydroxy, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] isn't it.

[0338] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is selected from pyrrolidine, 3-pyrroline, 2-pyrroline, 2H-pyrrole, 1H-pyrrole, tetrahydrofuran, furan, tetrahydrothiophene, and thiophene, any one of which is selected from halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0339] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing one oxygen atom, wherein the optionally substituted 5-membered heterocycle is selected from tetrahydrofuran and furan, any one of which is selected from halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0340] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from the group consisting of tetrahydrofuran and furan (halogen, -OR 31 , and C 1~10 In some embodiments, the optionally substituted 5-membered heterocycle is selected from tetrahydrofuran (halogen, -OR 31 , and C 1~10 In some embodiments, -OR is optionally substituted with one or more substituents independently selected from alkyl.31 R 31 is hydrogen and C 1~10 In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0341] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing one nitrogen atom, wherein the optionally substituted 5-membered heterocycle is selected from pyrrolidine, 3-pyrroline, 2-pyrroline, 2H-pyrrole, and 1H-pyrrole, any one of which is selected from halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C 1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0342] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the optionally substituted 5-membered heterocycle is selected from pyrrolidine, 3-pyrroline, 2-pyrroline, 2H-pyrrole, and 1H-pyrrole, any one of which is selected from halogen, —OR 31 , and C 1~10 alkyl (each of which is OR 31 In some embodiments, the aryl group is optionally substituted with one or more substituents independently selected from -OR 31 R 31 In each occurrence, C 1~10In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0343] In some embodiments of the compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is an optionally substituted 5-membered heterocycle containing one sulfur atom, wherein the optionally substituted 5-membered heterocycle is selected from tetrahydrothiophene and thiophene, any one of which is selected from halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -C(O)N(R 31 )2, N(R 31 )C(O)R 31 , -C(O)OR 31 , -OC(O)R 31 , -NO2, =O, -CN; and C1~10 Alkyl, C 2~10 Alkenyl and C 2~10 Alkynyl (each of which is halogen, -OR 31 , -N(R 31 )2, -C(O)R 31 , -NO2, =O, =S, -CN, C 3~10 optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle).

[0344] In some embodiments of the compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the optionally substituted 5-membered heterocycle is -OR 31 , =O, and C 1~10 In some embodiments, R is tetrahydrothiophene optionally substituted with one or more substituents independently selected from alkyl. 4 teeth, [ka] [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] is.

[0345] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] is selected from.

[0346] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy groups, the substituents at each occurrence being independently selected from hydroxy, halogen, —CN, —NO2, and C1-C6 alkoxy. 2 is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents at each occurrence being independently selected from hydroxy, halogen, —NO2, and C1-C6 alkoxy.

[0347] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 2 is selected from hydrogen and C1-C6 alkoxy. 2 is selected from hydrogen and -OMe. 2 is -OMe.

[0348] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 3is selected from hydrogen and optionally substituted C1-C6 alkoxy, the substituents at each occurrence being independently selected from hydroxy and C1-C6 alkoxy. 3 is selected from hydrogen and C1-C6 alkoxy.

[0349] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 3 is selected from C1-C6 alkoxy. 3 is -OMe.

[0350] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 5 is selected from hydrogen, hydroxy, and an optionally substituted C1-C6 alkoxy group, the substituents at each occurrence being independently selected from hydroxy, halogen, —CN, —NO2, and C1-C6 alkoxy.

[0351] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 5 is hydroxy.

[0352] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 6 and R 7 are each independently selected from hydrogen and hydroxy. 6 and R 7 are each hydrogen. 6 is hydrogen and R 7 is hydroxy. In some embodiments, R 6 and R 7 Let's get together and [ka] Form.

[0353] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] and optionally substituted 3- to 10-membered heterocycles. In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] In some embodiments of the compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 is selected from hydroxy.

[0354] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 is an optionally substituted 3- to 10-membered heterocycle. In some embodiments, the optionally substituted heterocycle is a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycle. In some embodiments, the optionally substituted 3- to 10-membered heterocycle is a 3- or 4-membered heterocycle, a 5- or 6-membered heterocycle, a 7- or 8-membered heterocycle, or a 9- or 10-membered heterocycle.

[0355] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1is an optionally substituted 5-6 membered heterocycle containing at least one heteroatom selected from oxygen, nitrogen, sulfur, boron, phosphorus, silicon, selenium, and any combination thereof. In some embodiments, the optionally substituted 5-6 membered heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, and any combination thereof.

[0356] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 The optionally substituted 5-6 membered heterocycle of formula (I) contains at least one heteroatom selected from nitrogen. 1 The optionally substituted 5- to 6-membered heterocycle is [ka] any of which is selected from hydroxy, halogen, —CN, —NO2, ═O, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, a 3-10 membered heterocycle, and C 3~10 and a 3- to 10-membered heterocycle, optionally substituted with one or more substituents independently selected from a carbocycle and a C 3~10 Each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, -CN, -NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy. In some embodiments, the one or more substituents are independently selected from hydroxy, ═O, C1-C6 alkyl, 3-8 membered heterocycle, and C 3~8 a carbocyclic ring, and the 3- to 8-membered heterocyclic ring and C 3~8 Each carbocycle is optionally substituted with one or more substituents independently selected from hydroxy, halogen, —CN, —NO, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and C1-C6 alkoxy.

[0357] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] In some embodiments of the compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is hydrogen, optionally substituted C1-C6 alkyl, and -P(=O)(R 24 )2 is selected.

[0358] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is hydrogen.

[0359] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is -P(=O)(R 24 )2 and R 24 is replaced as necessary 1~10 In some embodiments, R 1 teeth, [ka] is.

[0360] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, -OR 30 , with C being substituted as needed3~10 C1-C6 alkyl optionally substituted with one or more substituents selected from carbocycle and optionally substituted 3- to 10-membered heterocycle; R 30 is hydrogen and optionally substituted C 1~10 In some embodiments, R 1 R 22 is -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, and -OR 30 is a C1-C6 alkyl substituted with one or more substituents selected from:

[0361] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is -N(R 30 )2. In some embodiments, R 1 teeth, [ka] is.

[0362] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is -(O-CH2-(CH2) p ) nand n is 1 to 1000. In some embodiments, n is 1 to 800. In some embodiments, n is 1 to 500. In some embodiments, n is 1 to 300. In some embodiments, n is 1 to 100. In some embodiments, n is 1 to 50. In some embodiments, n is 1 to 25. In some embodiments, n is 3 to 1000. In some embodiments, n is 10 to 1000. In some embodiments, n is 50 to 1000. In some embodiments, n is 100 to 1000. In some embodiments, n is 200 to 1000. In some embodiments, n is 500 to 1000. In some embodiments, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100. In some embodiments, p is 1 to 1000. In some embodiments, p is 1 to 800. In some embodiments, p is 1 to 500. In some embodiments, p is 1 to 300. In some embodiments, p is 1 to 100. In some embodiments, p is 1 to 50. In some embodiments, p is 1 to 25. In some embodiments, p is 3 to 1000. In some embodiments, p is 10 to 1000. In some embodiments, p is 50 to 1000. In some embodiments, p is 100 to 1000. In some embodiments, p is 200 to 1000. In some embodiments, p is 500 to 1000. In some embodiments, p is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 100.

[0363] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is -(O-CH2-(CH2) p ) n -W, and -OR 30In some embodiments, R is a C1-C6 alkyl substituted with one or more substituents selected from 1 teeth, [ka] [ka] is selected from.

[0364] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is replaced as necessary 3~10 In some embodiments, optionally substituted C 3~10 Carbocyclic rings are C 3~6 In certain embodiments, C 3~6 The carbocyclic ring is unsaturated. 3~6 Carbocycles are saturated. In some embodiments, optionally substituted C 3~6 Carbocycles are: [ka] In some embodiments, R 1 R 22 is C1-C6 alkyl substituted with phenyl. In some embodiments, R 1 teeth, [ka] is selected from.

[0365] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22is a C1-C6 alkyl substituted with one or more substituents selected from an optionally substituted 3-6 membered heterocycle. In some embodiments, the optionally substituted 3-6 membered heterocycle contains at least one heteroatom selected from N, O, S, and any combination thereof.

[0366] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 22 is a C1-C6 alkyl substituted with one or more substituents selected from an optionally substituted 3-6 membered heterocycle, wherein the optionally substituted 3-6 membered heterocycle contains at least one heteroatom selected from N and O. In some embodiments, the 3-6 membered heterocycle is an optionally substituted C 1~6 Alkyl and -OR 30 In some embodiments, R 1 teeth, [ka] [ka] is selected from.

[0367] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] is selected from.

[0368] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] is selected from.

[0369] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] In some embodiments, R 1 R 20 is selected from hydrogen and optionally substituted C1-C3 alkyl. In some embodiments, R 1 R 21 is selected from hydrogen and optionally substituted C1-C3 alkyl. In some embodiments, R 1 R 21 is replaced as necessary 1~10 In some embodiments, R 1 R 21 -OR 30 , -N(R 30 )2, -(O-CH2-(CH2) p ) n -W, C substituted as needed 3~10 C substituted with one or more substituents selected from carbocycles and optionally substituted 3- to 10-membered heterocycles 1~10 In some embodiments, R 1 teeth, [ka] [ka] is selected from.

[0370] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] and R 1 R 21 is an optionally substituted 3- to 7-membered heterocycle. In some embodiments, the 3- to 7-membered heterocycle is -OR 30 and C, substituted as needed 1~10 In some embodiments, R is substituted with one or more substituents selected from alkyl. 1 teeth, [ka] is selected from.

[0371] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] In some embodiments, R 1 R 23 is an optionally substituted C1-C6 alkyl. In some embodiments, C1-C6 alkyl is —OR 30 , -N(R 30 )2, optionally substituted C 1~10 Alkyl, optionally substituted C 3~10 In some embodiments, R is substituted with one or more substituents selected from a carbocycle and a 3- to 10-membered heterocycle. 1 teeth, [ka] is selected from.

[0372] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 R 23 is an optionally substituted 3- to 7-membered heterocycle. In some embodiments, the 3- to 7-membered heterocycle is optionally substituted C1~10 In some embodiments, R is substituted with one or more substituents selected from alkyl. 1 teeth, [ka] is.

[0373] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] [ka] [ka] is selected from.

[0374] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] [ka] is selected from.

[0375] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] [ka] is selected from.

[0376] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] is selected from.

[0377] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] is selected from.

[0378] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 is -OH and [ka] In some cases, R 1 teeth, [ka] and R 22 is optionally substituted C1-C6 alkyl, preferably optionally substituted C 2~4 In some cases, R 1 teeth, [ka] and R 22 is a substituted C1-C6 alkyl, preferably a substituted C 2~4 In some cases, R 22 The above substituent is -OR 30 , -(O-CH2-(CH2) p ) n -W, -S(O)R30 , -S(O)2R 30 , =O, =S, =N(R 30 ), and —CN. In some cases, R 22 The above optional substituents are -OR 30 , -S(O)2R 30 and ═O. In some cases, R 22 The above optional substituents are -OR 30 , and -S(O)R 30 In some cases, -OR 30 and -S(O)R 30 R 30 is hydrogen and C 1~10 alkyl, 1~10 Alkyl is a halogen, -OH, -CN, -NO2, -NH2, =O, =S, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 and optionally substituted with one or more substituents independently selected from a carbocycle, a 3- to 10-membered heterocycle, and a -OR 30 and -S(O)R 30 R 30 In each occurrence, hydrogen and C 1~10 alkyl.

[0379] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 1 teeth, [ka] In some cases, R 1 teeth, [ka] is selected from.

[0380] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R′ and R″ at each occurrence are independently selected from hydrogen.

[0381] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from an optionally substituted C3-C5 carbocycle and an optionally substituted 4-5 membered heterocycle, and the optional substituents on ring A, at each occurrence, are selected from halogen, ═O, —OH, —OC 1~3 In some cases, Ring A is selected from an optionally substituted saturated C3-C5 carbocycle and an optionally substituted saturated 4-5 membered heterocycle, and the optional substituents on Ring A, at each occurrence, are selected from halogen, ═O, —OH, —OC 1~3 In some cases, for compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), the 4- to 5-membered heterocycle contains at least one heteroatom selected from oxygen and sulfur.

[0382] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] is selected from.

[0383] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] is selected from.

[0384] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] is selected from.

[0385] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), Ring A is selected from unsubstituted C3-C5 carbocycles and optionally substituted 4-5 membered heterocycles, and the optional substituents on the 4-5 membered heterocycles are selected from, at each occurrence, halogen, ═O, —OH, —OC 1~3 alkyl, and —CN.

[0386] In some embodiments of a compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), R 4 teeth, [ka] is selected from.

[0387] In some embodiments of a compound or salt of Formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from optionally substituted C3-C5 carbocycles.

[0388] In some embodiments of the compounds or salts of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG), ring A is selected from unsubstituted C3-C5 carbocycles. In some cases, z is selected from 0 and 1. In some cases, R 4 teeth, [ka] is selected from.

[0389] In some embodiments, the compound or salt of formula (L), (LA), (LB), (LC), (LD), (LE), (LF), or (LG) is [ka] [ka] [ka] [ka] is selected from. Compound groups 1, 2, and 3

[0390] Chemical entities having carbon-carbon or carbon-nitrogen double bonds can exist in Z or E forms (or cis or trans forms). Additionally, some chemical entities can exist in various tautomeric forms. Unless otherwise specified, the compounds described herein are intended to include all Z, E, and tautomeric forms as well.

[0391] "Isomers" are different compounds with the same molecular formula. "Stereoisomers" are isomers that differ only in the way their atoms are arranged in space. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. The term "(±)" is used to designate a racemic mixture when appropriate. "Diastereoisomers" or "diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is specified according to the Cahn-Ingold-Prelog RS system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified as either R or S. Resolved compounds whose absolute configuration is unknown can be designated as (+) or (-) depending on the direction (dextrorotatory or levorotatory) they rotate the plane of polarized light at the wavelength of the sodium D line. Certain compounds described herein contain one or more asymmetric centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms, which asymmetric centers can be defined in terms of absolute stereochemistry as (R)- or (S)-. The chemical entities, pharmaceutical compositions, and methods of the present invention are meant to include all possible such stereoisomers, including racemic mixtures, optically pure forms, diastereomeric mixtures, and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. The optical activity of a compound can be analyzed via any suitable method, including, but not limited to, chiral chromatography and polarimetry, to determine the predominance of one stereoisomer over another.

[0392] Unless stereochemistry is specified, molecules having a stereocenter described herein include isomers, such as enantiomers and diastereomers, enantiomeric mixtures including racemates, diastereomeric mixtures, and other mixtures thereof, to the extent that those skilled in the art can prepare them by routine experimentation. In certain embodiments, single enantiomers or diastereomers, i.e., optically active forms, can be obtained by asymmetric synthesis or by resolution of a racemate or diastereomeric mixture. Resolution of a racemate or diastereomeric mixture, if possible, can be achieved by conventional methods, such as crystallization in the presence of a resolving agent, or chromatography using, for example, a chiral high-pressure liquid chromatography (HPLC) column. Furthermore, a mixture of two enantiomers enriched in one of the two enantiomers can be purified by recrystallization and / or trituration to provide the major enantiomer in a more optically enriched form.

[0393] In certain embodiments, the compositions of the present disclosure may contain two or more enantiomers or diastereomers of a compound, with a single enantiomer or diastereomer comprising at least about 70%, at least about 80%, at least about 90%, at least about 98%, or at least about 99% or more by weight of the total weight of all stereoisomers. Methods for producing substantially pure enantiomers are well known to those skilled in the art. For example, a single stereoisomer, e.g., an enantiomer substantially free of its stereoisomer, can be obtained by resolution of a racemic mixture using methods such as the formation of diastereomers using an optically active resolving agent (Stereochemistry of Carbon Compounds, (1962) by EL Eliel, McGraw Hill; Lochmuller (1975) J. Chromatogr., 113(3): 283-302). Racemic mixtures of chiral compounds can be separated and isolated by any suitable method, including, but not limited to, (1) formation of ionic diastereomeric salts with the chiral compound and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing reagents, separation of the diastereomers, and conversion to pure stereoisomers, and (3) direct separation of substantially pure or enriched stereoisomers under chiral conditions. Another approach for separating enantiomers is to use a Diacel chiral column and elution with an organic mobile phase, such as that provided by Chiral Technologies (www.chiraltech.com) (fee-for-service).

[0394] "Tautomer" refers to a molecule that can shift protons from one atom of the molecule to another atom of the same molecule. In certain embodiments, the compounds presented herein exist as tautomers. In an environment where tautomerization is possible, a chemical equilibrium of tautomers exists. The exact ratio of tautomers depends on several factors, including physical conditions, temperature, solvent, and pH. Some examples of tautomeric equilibrium include: [ka] Includes:

[0395] The compounds disclosed herein may, in some embodiments, be present in different enriched isotopically enriched forms, e.g. 2 H, 3 H, 11 C. 13 C, and / or 14 The compound is used in an isotopic form enriched in C content. In a particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, and thus increase the duration of action of the drug.

[0396] Unless otherwise stated, compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, the replacement of hydrogen by deuterium or tritium, or the replacement of carbon by methyl ... 13 C or 14 Compounds having the present structures except for the replacement by a C-enriched carbon are within the scope of this disclosure.

[0397] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may contain isotopes of, for example, deuterium ( 2H), tritium ( 3 H), iodine-125( 125 I), or carbon-14 ( 14 It can be labeled with an isotope such as C. 2 H, 11 C. 13 C. 14 C. 15 C. 12 N, 13 N, 15 N, 16 N, 16 O. 17 O. 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl, 37 Cl, 79 Br, 81 Br, and 125 All isotopic substitutions are contemplated using I. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0398] In certain embodiments, the compounds disclosed herein are 2 replaced by H atoms 1 Having some or all of the H atoms. Synthetic methods for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the synthetic methods described below.

[0399] Deuterium-substituted compounds are described in Dean, Dennis C.; Editor. Recent Advances in Using various methods such as those described in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp, George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21, and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32. It is synthesized.

[0400] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to synthesize deuterium-containing compounds. Many deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0401] The compounds of the present invention also include crystalline and amorphous forms of the compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, nonsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, and mixtures thereof.

[0402] The present disclosure includes the salts of the compounds described herein, particularly pharmaceutically acceptable salts.The compounds of the present disclosure that have sufficient acidity, sufficient basicity, or both functional groups can react with some inorganic bases and inorganic and organic acids to form salts.Alternatively, compounds that are inherently charged, such as those that have quaternary nitrogen, can form salts with suitable counterions, such as halides, for example, bromides, chlorides, or fluorides, particularly bromides.

[0403] The methods and compositions described herein include the use of amorphous and crystalline forms (also known as polymorphs). The compounds described herein may take the form of pharmaceutically acceptable salts. Similarly, in some embodiments, active metabolites of these compounds with the same type of activity are included within the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated forms and solvated forms with pharmaceutically acceptable solvents such as water, ethanol, etc. Solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0404] In certain embodiments, a compound or a salt of a compound may be a prodrug, for example, a hydroxyl in the parent compound is presented as an ester or carbonate, or a carboxylic acid present in the parent compound is presented as an ester. The term "prodrug" is intended to encompass compounds that are converted to the pharmaceuticals of the present disclosure under physiological conditions. One method for making a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal, such as a specific target cell of the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids, and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0405] Prodrugs are often useful because in some situations they may be easier to administer than the parent drug. For example, they may be bioavailable by oral administration, whereas the parent drug is not. Prodrugs can help enhance the cell permeability of the compound compared to the parent drug. Prodrugs can also have improved solubility in pharmaceutical compositions compared to the parent drug. Prodrugs can be designed as reversible drug derivatives for use as modifiers to enhance drug transport to site-specific tissues or increase drug residence time in cells.

[0406] In some embodiments, the prodrug design increases the lipophilicity of the pharmaceutical agent, hi some embodiments, the prodrug design increases the effective water solubility. See, for example, Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the See ACS Symposium Series, and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987. According to another embodiment, the present disclosure provides a method for producing the compounds defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0407] Synthetic chemistry transformations and methods useful for synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989), T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991), L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994), and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995). Pharmaceutical Formulations of Compounds of Groups 1, 2, and 3

[0408] A compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) can be formulated into any suitable pharmaceutical formulation. Pharmaceutical formulations of the present disclosure typically contain an active ingredient (e.g., a compound or salt of any one of the formulas described herein) and other suitable additives, including, but not limited to, inert solid diluents and fillers, diluents, sterile aqueous solutions and various organic solvents, permeation enhancers, antioxidants, solubilizing agents, and the like. The composition contains one or more pharmaceutically acceptable excipients or carriers, including a stimulating agent, as well as an adjuvant.

[0409] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I) of the first aspect, Formula (X) of the second aspect, Formula (L) of the third aspect, etc.) is formulated with an agent that inhibits decomposition of the compound or salt. In certain embodiments, the compound or salt is formulated with one or more antioxidants. Acceptable antioxidants include, but are not limited to, citric acid, d,I-α-tocopherol, BHA, BHT, monothioglycerol, ascorbyl palmitate, ascorbic acid, and propyl gallate. In certain embodiments, the formulation contains 0.1-30%, 0.5-25%, 1-20%, 5-15%, or 7-12% (wt / wt) CCI-779, 0.5-50%, 1-40%, 5-35%, 10-25%, or 15-20% (wt / wt) water-soluble polymer, 0.5-10%, 1-8%, or 3-5% (wt / wt) surfactant, and 0.001%-1%, 0.01%-1%, or 0.1%-0.5% (wt / wt) antioxidant. In certain embodiments, the antioxidant in the formulations of the present invention is used at a concentration ranging from 0.001% to 3% wt / wt.

[0410] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I) of the first aspect, Formula (X) of the second aspect, Formula (L) of the third aspect, etc.) is formulated with a pH adjuster to maintain a pH of about 4 to about 6. Acceptable pH adjusters include, but are not limited to, citric acid, sodium citrate, dilute HCl, and other weak acids or bases capable of buffering a solution containing a compound or salt of the present disclosure to a pH in the range of about 4 to about 6.

[0411] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I) of the first aspect, Formula (X) of the second aspect, Formula (L) of the third aspect, etc.) is formulated with a chelating agent or other material capable of binding metal ions, such as ethylenediaminetetraacetic acid (EDTA) and salts thereof, which can enhance the stability of a compound or salt of any one of the formulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.).

[0412] Pharmaceutical preparations can be provided in any suitable form, and the form can vary depending on the route of administration. In some embodiments, the pharmaceutical compositions disclosed herein can be formulated into a dosage form for administration to a subject. In some embodiments, the pharmaceutical compositions are formulated for oral, intravenous, intraarterial, aerosol, parenteral, oral buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, intranasal, pulmonary, transmucosal, inhalation, and / or intraperitoneal administration. In some embodiments, the dosage form is formulated for oral administration. For example, the pharmaceutical composition can be formulated into the form of a pill, tablet, capsule, inhalant, liquid suspension, liquid emulsion, gel, or powder. In some embodiments, the pharmaceutical composition can be formulated as a unit dosage in liquid, gel, semi-liquid, semi-solid, or solid form.

[0413] The amount of a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) will depend on the mammal being treated, the severity of the disorder or condition, the rate of administration, the pharmacokinetics of the compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.), and the discretion of the prescribing physician.

[0414] In some embodiments, a pharmaceutically acceptable carrier for a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), Formula (I), Formula (X), Formula (L), etc.) can include a physiologically acceptable compound that is an antioxidant.

[0415] In some embodiments, the present disclosure provides a pharmaceutical composition for oral administration containing at least one compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) and a pharmaceutical excipient suitable for oral administration. The composition may be in solid, liquid, gel, semi-liquid, or semi-solid form. In some embodiments, the composition further comprises a second agent.

[0416] Pharmaceutical compositions of the present disclosure suitable for oral administration can be presented as powders or granules, solutions or suspensions in aqueous or non-aqueous liquids, oil-in-water or water-in-oil liquid emulsions, or dispersible powders or granules, or as syrups or elixirs, or as separate dosage forms, such as hard or soft capsules, cachets, lozenges, or tablets, or as liquids or aerosol sprays, each containing a predetermined amount of the active ingredient. Such dosage forms can be prepared by any of the formulation methods, which typically include combining the active ingredient(s) with the carrier. Generally, the compositions are prepared by uniformly and intimately mixing the active ingredient(s) with a liquid carrier or finely divided solid carrier, or both, and then, if necessary, shaping the product into the desired presentation. For example, tablets can be prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredient(s) in a free-flowing form, e.g., powder or granules, optionally mixed with excipients such as, but not limited to, binders, lubricants, inert diluents, and / or surface-active or dispersing agents. Molded tablets can be made by molding in a suitable machine a mixture of a powdered compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.), moistened with an inert liquid diluent.

[0417] In some embodiments, the present disclosure provides a pharmaceutical composition for injection, comprising a compound or salt of any one of the formulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) and a pharmaceutical excipient suitable for injection. The components and amounts of the drugs in the composition are as described herein.

[0418] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) may be formulated for injection as an aqueous or oily suspension, emulsion using sesame oil, corn oil, cottonseed oil, or peanut oil, as well as elixirs, mannitol, dextrose, or sterile aqueous solutions, and similar pharmaceutical vehicles.

[0419] Physiological saline solutions are also conventionally used for injection. Ethanol, glycerol, propylene glycol, liquid polyethylene glycol, etc. (and suitable mixtures thereof), cyclodextrin derivatives, and vegetable oils can also be used. Proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, to maintain the required particle size in the case of dispersions, and by the use of surfactants. Prevention of microbial action can be achieved by various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, etc.

[0420] Pharmaceutical compositions can also be prepared from a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) and one or more pharmaceutically acceptable excipients suitable for transdermal, inhalation, sublingual, buccal, rectal, intraosseous, intraocular, intranasal, epidural, or intraspinal administration. Preparations for such pharmaceutical compositions are well known in the art. For example, see Anderson, Philip O.; Knoben, James E.; Troutman, William G, eds., Handbook of Clinical Drug Data, Tenth Edition, McGraw-Hill, 2002; Pratt and Taylor, eds., Principles of Drug Action, Third Edition, Churchill Livingston, New York, 1990; Katzung, ed., Basic and Clinical Pharmacology, Ninth Edition, McGraw Hill, 2003, Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw Hill, 2001, Remingtons Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins., 2000, Martindale, The Extra Pharmacopoeia, Thirty-Second Edition (The Pharmaceutical Press, London, (1999).

[0421] The present disclosure also provides kits. The kits may include a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) and one or more additional agents in suitable packaging accompanied by written materials, which may include instructions for use, a discussion of clinical studies, a list of side effects, etc. Such kits may also include information, such as scientific references, package inserts, clinical trial results, and / or summaries thereof, demonstrating or establishing the activity and / or benefits of the composition and / or describing dosage, administration, side effects, drug interactions, or other information useful to healthcare providers. Such information may be based on the results of various studies, for example, studies using experimental animals, including in vivo models, and studies based on human clinical trials. The kits may further contain another agent. In some embodiments, the compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) and the agent are provided as separate compositions in separate containers within the kit. In some embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) and a drug are provided as a single composition in a container within a kit. Additional items for appropriate packaging and use (e.g., measuring cups for liquid preparations, foil wrappers to minimize exposure to air, etc.) are known in the art and can be included in the kit. The kits described herein can be provided, sold, and / or promoted to healthcare providers, including physicians, nurses, pharmacists, prescribing personnel, etc. Kits can also, in some embodiments, be sold directly to consumers. Therapeutic Applications of Groups 1, 2, and 3 Compounds

[0422] In one aspect, the disclosure provides a method of inhibiting mTORC1, comprising administering a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.). In one aspect, the disclosure provides a method of inhibiting mTORC1 without significantly modulating mTORC2, comprising administering a compound or salt of any one of the formulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.). In certain embodiments, the compounds and salts of the disclosure do not significantly inhibit mTORC2.

[0423] Without being bound by any particular mechanism, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) may exhibit reduced side effects compared to rapamycin. In particular, the compounds or salts of the present disclosure do not significantly affect the gastrointestinal tract and / or cardiac system. In certain embodiments, the compounds of the present disclosure may be administered at higher doses or for longer periods than those prescribed for rapamycin. For example, for example, for two months or more, four months or more, six months or more, one year or more, or two years or more, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) may be administered once daily, every other day, once weekly, or once every two weeks for a period of time, such as two months or more, four months or more, six months or more, one year or more, or two years or more. For examples of contemplated dosages, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) may be administered at doses that are 30% or more, 50% or more, 80% or more than the rapamycin dosage indicated for the same indication.

[0424] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) is administered to a subject in need thereof to treat a tauopathy (including but not limited to, Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy (PSP), corticobasal degeneration, corticobasal syndrome, frontotemporal dementia, frontotemporal lobar degeneration (FTLD) including but not limited to FTLD-17, behavior variant FTD, primary progressive aphasia (semantic, agrammatic or language aphasia), Decreased type), argyrophilic granule disease, Pick's disease, globular glial tauopathies, primary age-related tauopathies (including neurofibrillary tangle dementia), chronic traumatic encephalopathy (CTE) - including traumatic brain injury and age-related tau astrogliopathy), mTOR opathies (including but not limited to tuberous sclerosis complex (TSC)), mTOR opathies associated with epileptic seizures, focal cortical dysplasia (FCD), ganglioglioma, hemimegalencephaly, neurofibromatosis type 1, Sturge-Weber syndrome, Cowden syndrome, PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy), familial multiple discoid fibromas (FMDF) , epilepsy / epileptic seizures (both genetic and acquired forms of diseases such as familial focal epilepsy, epileptic spasms, infantile spasticity (IS), status epilepticus (SE), temporal lobe epilepsy (PLE) and absence epilepsy), rare diseases associated with dysfunction of mTORC1 activity (e.g., lymphangioleiomyomatosis (LAM), Leigh syndrome, Friedreich ataxia, Diamond-Blackfan anemia, etc.), metabolic diseases (e.g., obesity, type II diabetes, etc.), autoimmune and inflammatory diseases (e.g., systemic lupus erythematosus (SLE)), mTORC1 pathway (e.g., leukemia, multiple sclerosis (MS), psoriasis, etc.), cancer, fungal infections, proliferative diseases, maintenance of immunosuppression, transplant rejection, traumatic brain injury, autism, lysosomal storage diseases and neurodegenerative diseases associated with overactivation of mTORC1 (e.g., Parkinson's, Huntington's disease, etc.), abnormal compound accumulation, dysfunction of the autophagic mechanism, and generally, disorders that can be modulated by selective inhibition of the mTORC1 pathway.

[0425] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) is administered to a subject in need thereof for the treatment and / or prevention of a tauopathy selected from the group consisting of progressive supranuclear palsy, dementia pugilistica (chronic traumatic encephalopathy), frontotemporal dementia, Ritiko-Bodig disease (Parkinson-dementia complex of the Gam Islands), tangle-predominant dementia (NFT similar to Alzheimer's disease but without plaques), ganglioglioma and gangliocytoma, meningioangiomatosis, subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis complex, Pick's disease, corticobasal degeneration (in which tau protein is deposited in the form of inclusions within distended or "ballooned" neurons), Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal dementia, and frontotemporal lobar degeneration.

[0426] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) is administered to a subject in need thereof for the treatment and / or prevention of a tauopathy selected from the group consisting of Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy (PSP), corticobasal degeneration, corticobasal syndrome, frontotemporal dementia, frontotemporal lobar degeneration (FTLD) including but not limited to FTLD-17, behavioral FTD, primary progressive aphasia (semantic, agrammatic, or hypolinguistic), argyrophilic grain disease, Pick's disease, globular glial tauopathy, primary age-related tauopathy (including neurofibrillary tangle dementia), chronic traumatic encephalopathy (CTE) - traumatic brain injury, and age-related tauastrogliopathy.

[0427] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) is administered to a subject in need thereof for the treatment and / or prevention of an mTOR opopathy. The mTOR opopathy may be, for example, tuberous sclerosis, focal cortical dysplasia, or PTEN (phosphatase and tensin homolog) disease. The mTOR opopathy may be a disease or disorder described elsewhere herein.

[0428] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) is administered to a subject in need thereof for the treatment and / or prevention of cancer.Non-limiting examples of cancer include acute lymphocytic leukemia (ALL); acute myeloid leukemia; adrenocortical carcinoma; astrocytoma, childhood cerebellar or cerebral; basal cell carcinoma; bladder cancer; bone tumors, osteosarcoma / malignant fibrous histiocytoma; brain cancer; brain tumors, e.g., cerebellar astrocytoma, malignant glioma, ependymoma, medulloblastoma, gliomas of the visual pathway and hypothalamus; brain stem glioma; breast cancer; bronchial adenoma / carcinoid; Burkitt's lymphoma; cerebellar astrocytoma; cervical cancer; cholangiocarcinoma; chondrosarcoma; chronic lymphocytic leukemia; chronic myelogenous leukemia; chronic myeloproliferative disorder; colon cancer; cutaneous T cell lymphoma; endometrial cancer; ependymoma; esophageal cancer; eye cancers, e.g., intraocular melanoma and retinoblastoma; gallbladder cancer; glioma; hairy cell leukemia; head and neck cancer; heart cancer; hepatocellular (liver) cancer; Hodgkin's lymphoma; hypopharyngeal cancer; islet cell carcinoma (endocrine pancreas); Kaposi's sarcoma; kidney cancer (renal cell carcinoma); laryngeal cancer; leukemias, e.g., acute lymphoblastic, acute myeloid, chronic lymphocytic, chronic myeloid, and hairy cell; lip and oral cavity cancer; liposarcoma; lung cancers, e.g., non-small cell and small cell; lymphomas, e.g., AIDS-related, Burkina Faso, and others. Lymphoma, cutaneous T-cell, Hodgkin's and non-Hodgkin's, macroglobulinemia, malignant fibrous histiocytoma / osteosarcoma of bone; melanoma; Merkel cell carcinoma; mesothelioma; multiple myeloma / plasma cell neoplasm; mycosis fungoides; myelodysplastic syndrome; myelodysplastic / myeloproliferative disease; myeloproliferative disorder, chronic; nasal cavity and paranasal sinus cancer; nasopharyngeal carcinoma; neuroblastoma; oligodendroglioma; oropharyngeal cancer; osteosarcoma / malignant fibrous histiocytoma of bone; ovarian cancer; pancreatic cancer; parathyroid cancer; pharyngeal cancer; pheochromocytoma; pituitary adenoma; plasma cell neoplasm; pleuropulmonary blastoma; prostate cancer; rectal cancer ;renal cell carcinoma (kidney cancer);renal pelvis and ureter, transitional cell carcinoma;rhabdomyosarcoma;salivary gland cancer;sarcoma, Ewing family of tumors;sarcoma, Kaposi's;sarcoma, soft tissue;sarcoma, uterine;Sezary syndrome;skin cancer (non-melanoma);skin cancer;small intestine cancer;soft tissue sarcoma;squamous cell carcinoma;squamous cell cervical carcinoma of unknown primary, metastatic;gastric cancer;testicular cancer;throat cancer;thymoma and thymic carcinoma;thymoma;thyroid cancer;thyroid cancer, childhood;uterine cancer;vaginal cancer;Waldenstrom's macroglobulinemia;Wilms' tumor, and any combination thereof.

[0429] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I) of the first aspect, Formula (X) of the second aspect, Formula (L) of the third aspect, etc.) is administered to a subject in need thereof for the treatment and / or prevention of seizures and / or seizure-related disorders. Seizure-related disorders may include, but are not limited to, West syndrome, focal cortical dysplasia (FCD), tuberous sclerosis complex (TSC), childhood absence epilepsy, benign focal epilepsy of childhood, juvenile myoclonic epilepsy (JME), temporal lobe epilepsy, frontal lobe epilepsy, refractory epilepsy, Lennox-Gastaut syndrome, occipital lobe epilepsy, Proteus syndrome, hemimegalencephaly syndrome (HMEG), megalencephaly syndrome (MEG), megalencephaly-capillary malformation (MCAP), megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), and PTEN disorders.

[0430] The compound is suitable for use in the treatment and / or prevention of disorders involving fibrosis and / or inflammation (e.g., liver and kidney disorders) according to any of the therapeutic compounds disclosed herein. Disorders may include, but are not limited to, liver fibrosis (which may occur in end-stage liver disease), cirrhosis, toxic liver failure, nonalcohol-related fatty liver disease (NASH), and alcohol-related fatty liver disease. Another example may be renal fibrosis resulting from acute kidney injury, chronic kidney disease, or diabetic nephropathy, which may induce renal fibrosis and inflammation. Disorders may include polycystic kidney disease, ischemia / reperfusion injury, transplantation, adriamycin nephropathy, unilateral ureteral obstruction (UUO), glomerulopathy, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), and mesangial lupus proliferative nephritis.

[0431] The compounds are consistent with any of the therapeutic compounds disclosed herein for use in the treatment and / or prevention of acute or chronic organ or tissue transplant rejection, e.g., heart, lung, combined heart-lung, liver, kidney, pancreas, skin or cornea transplants, prevention of graft-versus-host disease, such as after bone marrow transplantation.

[0432] The compounds are consistent with any of the therapeutic compounds disclosed herein for use in the treatment and / or prevention of autoimmune and / or inflammatory conditions, particularly inflammatory conditions having an etiology that may include an autoimmune component, such as arthritis (e.g., rheumatoid arthritis, chronic progressive arthritis, and osteoarthritis) and rheumatic diseases. Examples include autoimmune hematological disorders (e.g., including hemolytic anemia, aplastic anemia, pure red cell anemia, and idiopathic thrombocytopenia), systemic lupus erythematosus, polychondritis, scleroderma, Wegener's granulomatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, psoriasis, Stevens-Johnson syndrome, idiopathic sprue, and autoimmune inflammatory bowel disease (e.g., including ulcerative colitis and Crohn's disease). These may include endocrine ophthalmopathy, Graves' disease, sarcoidosis, multiple sclerosis, primary biliary cirrhosis, juvenile diabetes mellitus (type 1 diabetes mellitus), uveitis (anterior and posterior), keratoconjunctivitis sicca and vernal conjunctivitis, interstitial pulmonary fibrosis, psoriatic arthritis, glomerulonephritis (with or without nephrotic syndrome, including, for example, idiopathic nephrotic syndrome or minimal change nephropathy) and juvenile dermatomyositis.

[0433] The compounds conform to any of the therapeutic compounds disclosed herein for use in the treatment and / or prevention of a mitochondrial disease or disorder.

[0434] The compounds are consistent with any of the therapeutic compounds disclosed herein for use in the treatment and / or prevention of smooth muscle cell proliferation and migration leading to vascular intimal hyperplasia, vascular occlusion, occlusive coronary atherosclerosis, or restenosis.

[0435] In certain embodiments, the present disclosure provides a method for treating the disease characterized by the overactivation of mTORC1.The following references include the method for evaluating mTORC (for example, mTORC1) activity: T. O'Reilly et al., Translational Oncology, v3, i2, p 65-79, (2010); J. Peralba, Clinical Cancer Research, v9, i8, p 2887-2892 (2003); DR Moore et al., Acta Physiologica, v201, i3, p 365-372 (2010); M. Dieterlen., Clinical Cytometry, v82B, i3, p151-157, (2012), and each of them is incorporated herein by reference.

[0436] In certain embodiments, the present disclosure provides a method for treating age-related diseases. It can be established that modulation of mTORC1 signaling can extend the lifespan of a wide range of organisms, from flies to mammals, and delay the occurrence of age-related diseases, thus providing a therapeutic option for preventing or treating age-related diseases in humans. In recent clinical studies, Mannick et al. (mTOR inhibition improves immune function in the elderly, Sci Transl Med. 2014 Dec 24;6(268):268ra179. doi: 10.1126 / scitranslmed.3009892) showed that mTOR inhibition improves immune function in the elderly.

[0437] In certain embodiments, the present disclosure provides a method for treating mitochondrial diseases. Mitochondrial myopathy and mitochondrial stress are caused by mitochondrial damage, as described in Chinnery, PF (2015); EMBO Mol. Med. 7, 1503-1512, Koopman, WJ et al., 10 (2016); EMBO Mol. Med. 8, 311-327, and Young, MJ, and Yound and Copeland, WC (2016); Curr. Opin. Genet. Dev. 38, 52-62. It can be a disability.

[0438] In certain embodiments, the present disclosure provides a method for treating autophagic disorders. In some cases, the autophagic disorders may include autophagic disorders that result in mitochondrial damage, lysosomal storage diseases, cancer, Crohn's disease, etc. In some cases, the autophagic disorder may be as described in Jiang P. & Mizushima, N., Autophagy and human diseases, Cell Research volume 24, p.69-79 (2014).

[0439] In certain embodiments, the compounds or salts of the present disclosure are used to induce heterodimerization of the FRB domains of FKBP12 and mTOR. Chemical induction of dimerization (CID) can be used as a biological tool to spatially manipulate specific molecules, such as peptides and polypeptides, within cells at precise times to control specific activities. Uses of CID include experimental investigations to elucidate cell systems and therapeutic uses to regulate cell-based therapies. Exemplary uses include cell activation, which is used to promote engraftment, treat diseases or conditions, or control or modulate the activity of therapeutic cells expressing chimeric antigen receptors or recombinant T cell receptors. The compounds of the present disclosure can be used in the development of triggering systems or molecular switches to control cell signaling.

[0440] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) is administered to a subject in need thereof to treat diabetic nephropathy, kidney-related type 1 diabetes and type 2 diabetes complications, autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), kidney diseases associated with cyst formation or cystogenesis, focal segmental kidney disease, urinary tract infection ... It is administered for the treatment and / or prevention of glomerulosclerosis (FSGS) and other diseases associated with sclerosis of the kidney (glomerulopathies, IgA nephropathy, mesangial lupus proliferative nephritis), laminopathies, age-related macular degeneration (AMD), diabetic macular edema, diabetic retinopathy, glaucoma, age-related retinal diseases, immune system aging, respiratory tract infections, urinary tract infections, heart failure, osteoarthritis, pulmonary arterial hypertension (PAH), and / or chronic obstructive pulmonary disease (COPD).

[0441] In certain embodiments, a compound or salt of any one of the formulas or subformulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.) is administered to a subject in need thereof for the treatment and / or prevention of lymphangioleiomyomatosis (LAM) and / or polycystic kidney disease.

[0442] The use of rapamycin as a dimerizer is limited by the side effects associated with mTOR inhibition.mTOR inhibition may reduce cell growth and proliferation, and possible immunosuppression.In contrast, the compounds of the present disclosure may show advantages over rapamycin due to their higher selectivity for mTOR1 than mTOR2.mTOR2 inhibition is associated with the negative side effects associated with rapamycin.The compounds described in the present invention are selective for mTOR1 and have minimal effect on mTOR2.

[0443] The term "multimerize" or multimerization refers to the dimerization of two peptides or polypeptides, or the multimerization of more than two peptides or polypeptides, for example, the dimerization of the FRB domains of FKBP12 and mTOR.

[0444] The inducible FKBP12 / FRB-based multimerization system can also be incorporated into chimeric antigen receptor (CAR) T cells, which can be used, for example, in immunotherapy applications. One type of immunotherapy is adoptive cell transfer, in which a subject's immune cells are collected and modified ex vivo, e.g., into CAR-modified T cells, to provide specific, targeted tumor cell killing when the modified cells are returned to the body. T cells from the patient's blood can be extracted and genetically engineered to express a CAR on the cell surface. CAR components typically include an extracellular antibody-derived single-chain variable fragment (scFv) that specifically recognizes a target tumor cell antigen and one or more signaling sequences from multicellular T cells fused to the scFv. Binding of the scFv region to the antigen activates the T cells via the signaling domain of the CAR. In certain embodiments, the compounds of the present disclosure can be administered to cells to activate CAR-T cells via the FKBP12 / FRB-based multimerization system. In certain embodiments, the present disclosure provides methods of activating the growth of cells containing an FKBP protein fusion and an FRB fusion protein, e.g., CAR-T cells, by contacting the cells with a compound or salt of any one of the formulae described herein (e.g., Formula (I), Formula (X), Formula (L), etc.).

[0445] In some cases, it is beneficial to enhance the activity of therapeutic cells. For example, co-stimulating polypeptides can be used to enhance the activation of T cells and CAR-expressing T cells against antigens, thereby increasing the efficacy of adoptive immunotherapy. These treatments are used, for example, to treat tumors for elimination and to treat cancer and hematological disorders, but these treatments can have negative side effects. Excessive on-target effects, such as those directed at large tumor volumes, can lead to cytokine storms associated with tumor lysis syndrome (TLS), cytokine release syndrome (CRS), or macrophage activation syndrome (MAS). In some cases of therapeutic cell-induced adverse events, rapid and nearly complete elimination of therapeutic cells is necessary. If the number of transplanted CAR-T cells needs to be reduced, a triggering ligand can be administered to the treated subject, thereby specifically inducing apoptosis of the modified T cells. For example, multimeric forms of FRB and / or FKBP12 or their variants, which are ligand-binding domains fused to a caspase protein and expressed in modified therapeutic cells, such as those described in WO2020 / 076738, can serve as a scaffold that allows spontaneous dimerization and activation of the caspase units upon recruitment via FRB and / or FKBP12 with a chemical inducer, such as a compound or salt of any one of the formulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.). In certain embodiments, the present disclosure provides a method of inhibiting the growth of cells containing an FKBP protein fusion and an FRB fusion protein by contacting the cells with a compound or salt of any one of the formulas described herein (e.g., Formula (I), Formula (X), Formula (L), etc.). [Example]

[0446] The following examples are offered to illustrate, but not to limit, the claimed invention. It will be recognized that these preparation methods are exemplary and not limiting. Using the teachings provided herein, numerous other methods of producing the rapamycin analogs described herein will be available to those skilled in the art.

[0447] When absolute stereochemistry is specified, it is assigned by analogy based on analytical data for rapamycin (eg, at C16 and C28 of compounds described elsewhere herein). Example 1 NMR spectroscopy

[0448] 1 H NMR spectra were recorded at 400 MHz on a Bruker Avance III NMR spectrometer. Samples were prepared in deuterated chloroform (CDCl) or dimethyl sulfoxide (DMSO-d), and raw data were processed using MNova NMR software. Example 2 UPLC-MS analysis

[0449] LCMS analysis was performed on a Waters Acquity UPLC system consisting of an Acquity i-Class Sample Manager-FL, an Acquity i-Class Binary Solvent Manager, and an Acquity i-Class UPLC Column Manager. UV detection was achieved using an Acquity i-Class UPLC PDA detector (scanning from 210 to 400 nm), and mass detection was achieved using an Acquity QDa detector (mass scanning from 100 to 1250 Da, simultaneously in positive and negative modes). Separation of the analytes was achieved using a Waters Acquity UPLC CSH C18 column (2.1 x 100 mm), 1.7 μm particle size.

[0450] Samples were prepared by dissolving in 1 mL of MeOH or MeCN (with or without sonication). The resulting solution was filtered through a 0.2 μm syringe filter before analysis. All solvents used (including formic acid) were HPLC grade.

[0451] Details of the analytical methods used in this study are presented below.

[0452] Method 1: 0.1% v / v formic acid in water [eluent A], 0.1% v / v formic acid in MeCN [eluent B], flow rate 0.8 mL / min, injection volume 2 μL and equilibration time 1.5 min between samples. [Table 1] Example 3 Preparative HPLC

[0453] Method 1: Compounds were purified by reverse-phase column chromatography on a Gemini NX C18 (30 mm x 150 mm, 5 μm) cartridge eluted with a HO (0.2% formic acid):MeCN gradient. The gradient was selected based on the analytical separation. Example 4 SFC

[0454] SFC was performed using the following method.

[0455] Method 1: Greensep 2EP (19 mm x 100 mm, 5 μm), CO2 / MeCN. The gradient was selected based on the analytical separation. Synthesis of intermediates Example 5 Synthesis of 2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonyl chloride [ka]

[0456] A mixture of 1-bromo-2-[2-(2-methoxyethoxy)ethoxy]ethane (2.50 g, 11.0 mmol) and sodium sulfite [NaSO] (1.39 g, 11.0 mmol) in stirred HO (13.4 mL) was heated to reflux for 18 h. The mixture was concentrated under reduced pressure, then dissolved in ethanol (20 mL) and concentrated to dryness. A 1:1 mixture of TBME / hexane (20 mL) was added, and the mixture was again concentrated to dryness. This final step was repeated to give sodium 2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonate as a solid (as a mixture with sodium bromide), which was used without analysis or purification. POCl (6.8 mL, 74.1 mmol) was added, and the mixture was heated at 70 °C for 4 h and then stirred at rt overnight. The mixture was carefully added to ice-HO (50 mL), and the product was then extracted with EtOAc (3 x 50 mL). The combined organic extracts were dried (NaSO) and concentrated under reduced pressure to give 2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonyl chloride (1.90 g, 70%) as an oil. 1 H NMR (400 MHz, CDCl3) δ 4.14 - 4.04 (m, 2H), 3.99 (t, J = 6.0 Hz, 2H), 3.78 - 3.69 (m, 2H), 3.69 - 3.61 (m, 4H), 3.55 (dd, J = 5.7, 3.4 Hz, 2H), 3.38 (s, 3H). Example 6 Synthesis of N-tert-butyl-2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonamide [ka]

[0457] To a solution of tert-butylamine (0.70 mL, 4.43 mmol) in THF (4.4 mL) was added 2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonyl chloride (0.84 g, 2.21 mmol) dropwise at -20 °C. The mixture was warmed to rt and stirred overnight. The resulting precipitate was filtered, the filter cake was washed with THF (10 mL), and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20–100% EtOAc in hexanes, stained with acidic vanillin solution) to give N-tert-butyl-2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonamide (0.144 g, 23%) as an oil. 1 H NMR (400 MHz, CDCl3) δ 4.77 (s, 1H), 3.90 (t, J = 5.8 Hz, 2H), 3.64 (d, J = 11.5 Hz, 6H), 3.59 - 3.54 (m, 2H), 3.38 (s, 3H), 3.30 (t, J = 5.8 Hz, 2H), 1.37 (s, 9H). Example 7 Synthesis of 2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonamide [ka]

[0458] To N-tert-butyl-2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonamide (144 mg, 0.51 mmol) in DCM (2 mL) was added TFA (0.39 mL, 5.1 mmol), and the mixture was stirred at rt for 18 h. The mixture was concentrated under reduced pressure and then azeotroped with toluene (2 × 10 mL) and DCM (10 mL) to give 2-[2-(2-methoxyethoxy)ethoxy]ethane-1-sulfonamide as an oil, which still contained some TFA but was used without further purification. 1H NMR (400 MHz, CDCl3) δ 4.06 - 3.95 (m, 2H), 3.75 - 3.58 (m, 9H), 3.43 (s, 3H), 3.40 - 3.34 (m, 2H). Example 8 Synthesis of 3-methanesulfonylpropyl trifluoromethanesulfonate [ka]

[0459] 3-Methanesulfonylpropan-1-ol (2.00 g, 14.5 mmol) and 2,6-dimethylpyridine (1.80 mL, 15.2 mmol) were dissolved in anhydrous DCM (25 mL) and cooled to −30° C. Trifluoromethanesulfonyl trifluoromethanesulfonate (2.3 mL, 13.9 mmol) was added dropwise, and the mixture was warmed to −10° C. over 50 minutes. The mixture was quenched with HO (25 mL), and the layers were separated. The organic layer was washed with HO (25 mL) and brine (25 mL), dried (NaSO), filtered, and concentrated under reduced pressure to give 3-methanesulfonylpropyl trifluoromethanesulfonate (3.05 g, 78%) as an oil. 1 H NMR (400 MHz, DMSO-d6) δ 4.36 (t, J = 6.0 Hz, 2H), 3.25 - 3.15 (m, 2H), 3.02 (s, 3H), 2.22 - 2.06 (m, 2H). 19 F NMR (376 MHz, DMSO-d6) δ -77.7 (s). Example 9 Synthesis of 3-[(tert-butyldimethylsilyl)oxy]propyl trifluoromethanesulfonate [ka]

[0460] To a solution of 3-[(tert-butyldimethylsilyl)oxy]propan-1-ol (5.21 g, 27.4 mmol) and DIPEA (6.0 mL, 34.2 mmol) in pentane (26 mL) was added triflic anhydride (5.1 mL, 30.5 mmol) at 0° C. The reaction mixture was stirred at this temperature for 2 h and then filtered through a Celite plug. The residue was dissolved in hexane (20 mL), filtered through a Celite plug, and then concentrated under reduced pressure to give 3-[(tert-butyldimethylsilyl)oxy]propyl trifluoromethanesulfonate (7.56 g, 86%) as an oil. Example 10 Synthesis of intermediate A [ka]

[0461] To a solution of rapamycin (4.00 g, 4.4 mmol) in EtOAc (120 mL) was added 1H-imidazole (1.30 g, 19.0 mmol), and the reaction mixture was cooled to 0 °C. TMSCl (2.2 mL, 17.5 mmol) was added over 10 min, and the reaction was stirred for 50 min. 0.5 M H2SO4 (8.0 mL, 4.0 mmol) was added dropwise over 10 min, and the mixture was stirred for 20 min. The mixture was washed sequentially with brine (120 mL), saturated sodium bicarbonate solution (120 mL), H2O (120 mL), and brine (120 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure, and the resulting solid was purified by silica gel column chromatography (30–60% EtOAc in heptane) to give Intermediate A (3.74 g, 87%) as a solid. 1 H NMR (400 MHz, DMSO-d6) δ 6.52 - 6.32 (m, 2H), 6.31 - 6.07 (m, 3H), 5.48 (dd, J = 12.6, 10.1 Hz, 1H), 5.21 - 4.86 (m, 3H), 4.67 - 4.56 (m, 1H), 4.17 - 3.95 (m, 3H), 3.70 - 3.60 (m, 1H), 3.54 - 3.41 (m, 1H), 3.36 - 3.33 (m, 3H), 3.31 - 3.26 (m, 1H), 3.24 - 3.14 (m, 4H), 3.13 - 2.98 (m, 4H), 2.87 - 2.78 (m, 1H), 2.76 - 2.66 (m, 1H), 2.49 - 2.42 (m, 1H), 2.41 - 2.30 (m, 1H), 2.29 - 2.18 (m, 1H), 2.17 - 2.08 (m, 1H), 2.07 - 2.02 (m, 1H), 1.97 - 1.73 (m, 6H), 1.72 - 1.47 (m, 11H), 1.46 - 1.22 (m, 6H), 1.16 - 0.94 (m, 7H), 0.93 - 0.69 (m, 13H), 0.64 - 0.54 (m, 1H), 0.00 (s, 9H). UPLC-MS (method 1): rt 6.47 min, m / z (ES+) 1003.8 [M +NH4] + (Example 11) Synthesis of intermediate B

change

[0462] To a solution of Intermediate A (2.00 g, 2.0 mmol) and DIPEA (3.4 mL, 19.0 mmol) in anhydrous DCM (25 mL) was added a solution of 3-methanesulfonylpropyl trifluoromethanesulfonate (4.93 g, 18.3 mmol) in anhydrous DCM (7.2 mL), and the mixture was stirred for 18 h. Amberlyst basic resin (15 g) was added, stirring was continued for 10 min, then the mixture was filtered, and the resin was washed with DCM (50 mL). The combined organic layers were washed with HO (2 × 50 mL) and brine (50 mL), then dried (NaSO), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (40–80% EtOAc in heptane) to give Intermediate B (1.15 g, 51%) as a solid. 1 H NMR (400 MHz, DMSO-d6) δ 6.52 - 6.33 (m, 2H), 6.29 - 6.08 (m, 3H), 5.48 (dd, J = 12.6, 10.1 Hz, 1H), 5.19 - 4.90 (m, 3H), 4.16 - 3.96 (m, 3H), 3.69 - 3.53 (m, 3H), 3.52 - 3.44 (m, 1H), 3.34 - 3.30 (s, 4H) 3.22 - 2.93 (m, 14H), 2.77 - 2.65 (m, 1H), 2.49 - 2.42 (m, 1H), 2.41 - 2.30 (m, 1H), 2.29 - 2.18 (m, 1H), 2.17 - 2.09 (m, 1H), 2.08 - 2.02 (m, 1H), 2.00 - 1.74 (m, 8H), 1.73 - 1.47 (m, 11H), 1.46 - 1.22 (m, 6H), 1.16 - 0.95 (m, 7H), 0.94 - 0.71 (m, 13H), 0.69 - 0.57 (m, 1H), 0.00 (s, 9H).UPLC-MS (Method 1): rt 6.56 min, m / z(ES+)112 3.8[M+NH4] + Example 12 Synthesis of intermediate C [ka]

[0463] To a solution of intermediate B (1.12 g, 1.00 mmol) in acetone (47 mL) was added 0.5 M sulfuric acid (1.8 mL, 0.90 mmol) at 0 °C, and the mixture was stirred for 2 h. The mixture was diluted with EtOAc (120 mL) and washed successively with saturated aqueous sodium bicarbonate (2 × 80 mL), HO (2 × 80 mL), and brine (80 mL). The organic layer was dried (NaSO) and then concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (20–100% EtOAc in hexanes) to give intermediate C [also known as compound 59] (0.91 g, 88%) as a solid. 1 H NMR (400 MHz, DMSO-d6) δ 6.52 - 6.34 (m, 2H), 6.29 - 6.06 (m, 3H), 5.47 (dd, J = 12.6, 9.6 Hz, 1H), 5.30 - 5.24 (m, 1H), 5.18 - 4.89 (m, 3H), 4.06 - 3.92 (m, 3H), 3.66 - 3.51 (m, 3H), 3.49 - 3.38 (m, 1H), 3.35 - 3.32 (m, 4H), 3.30 - 3.24 (m, 1H), 3.18 - 3.09 (m, 5H), 3.07 - 2.90 (m, 8H), 2.76 - 2.67 (m, 1H), 2.47 - 2.30 (m, 2H), 2.28 - 2.15 (m, 1H), 2.14 - 2.01 (m, 2H), 1.96 - 1.77 (m, 6H), 1.76 - 1.47 (m, 11H), 1.46 - 1.20 (m, 7H), 1.15 - 0.93 (m, 8H), 0.91 - 0.71 (m, 13H), 0.69 - 0.60 (m, 1H).UPLC-MS (Method 1): rt 4.0 2 min, m / z (ES+) 1051.7 [M+NH4] + Example 13 Synthesis of intermediate D [ka]

[0464] To a solution of Intermediate A (2.65 g, 2.69 mmol) in chlorobenzene (14 mL) was added DIPEA (2.1 mL, 11.8 mmol). The mixture was heated to 60° C., and then a solution of ...

Claims

1. A compound represented by the structure of formula X 【Chemistry 1】 or a pharma- ceutically acceptable salt thereof, L is selected from unsubstituted C 2-4 alkylene; R 1 is selected from -S(O)OH, -S(O) 2 OH, and -S(O) 2 C 1-6 alkyl, said C 1-6 alkyl being optionally substituted with one or more substituents selected from halogen, -OH, -NO 2 , =O, -O-C 1-6 alkyl; R 2 is selected from hydrogen and a C 1 -C 3 alkoxy group; R 3 is selected from hydrogen and a C 1 -C 6 alkoxy group; R ４ teeth, 【Chemistry 2】 is selected from z is 0, 1, 2, 3, 4 or 5; R5 is hydrogen, hydroxy, and optionally substituted C １ ~C ６ alkoxy groups, and the substituents, at each occurrence, are selected from hydroxy, halogen, —CN, —NO ２ , C １ ~C ６ Alkoxy groups, 3- to 10-membered heterocycles, and C ３～１０ carbocycle, said 3- to 10-membered heterocycle and C ３～１０ The carbocycles are each hydroxy, halogen, -CN, -NO ２ , C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C 1 -C 6 alkoxy, and C １ ~C ６ optionally substituted with one or more substituents independently selected from alkoxyC 1 -C 6 alkyl; R ６ and R ７ Together, 【Chemistry 3】 Forming R 25 is independently selected at each occurrence from hydrogen, optionally substituted C 1 -C 6 alkyl, -D-(CH 2 -CH 2 -G) y -V, optionally substituted C 3-20 carbocycle, and optionally substituted 3-20 membered heterocycle; When R 25 is optionally substituted C 1 -C 6 alkyl, the substituents on the C 1 -C 6 alkyl, at each occurrence, are independently selected from halogen, —OH, —CN, —NO 2 , —NH 2 , ═O, ═S, —C(O)N(R 31 ) 2 , —OC(O)N(R 31 ) 2 , —C(O)OR 31 , —P(O)(R 31 ) 2 , —C 1-10 haloalkyl, —O—C 1-10 alkyl, —O—C 1-10 alkyl-CN, —O—C 1-10 alkyl-C(O)OR 31 , C 2-10 alkenyl, C 2-10 alkynyl, C 3-20 carbocycle, and 3-20 membered heterocycle; When R 25 is an optionally substituted C 3-20 carbocycle or an optionally substituted 3-20 membered heterocycle, the substituents on the C 3-20 carbocycle and the 3-20 membered heterocycle at each occurrence are selected from the group consisting of halogen, -OR ３１ , -SR ３１ , -N(R ３１ ) ２ , -C(O)R ３１ , -C(O)N(R ３１ ) ２ , -N(R ３１ ) C(O)R ３１ , -C(O)OR ３１ , -OC(O)R ３１ , -S(O)R ３１ , -S(O) ２ R ３１ , -P(O)(OR ３１ ) ２ , -OP(O)(OR ３１ ) ２ , -NO ２ , =O, =S, =N(R ３１ ), -CN,C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, and C ２～６ alkynyl, D is selected from a bond and -O-; Each G is -O-, -NR ３２ -, -S-, and -SO ２ - independently selected from each y is selected from 1 to 20; Each V is hydrogen and optionally substituted -C １ ~C ６ alkyl, R 30 in each occurrence is hydrogen, C １～１０ Alkyl, C ２～１０ Alkenyl, C ２～１０ Alkynyl, C ３～１０ Carbocycles and 3- to 10-membered heterocycles, each of which is selected from the group consisting of halogen, —OH, —OSi(C 1 -C 6 alkyl) 3 , —CN, —NO ２ , -NH ２ , =O, =S, C １～１０ Alkyl, -C １～１０ Haloalkyl, —O—C １～１０ Alkyl, C ２～１０ Alkenyl, C ２～１０ Alkynyl, C ３～１０ optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; R' and R'' are independently selected at each occurrence from hydrogen, halogen, -OR 31 , and C 1-8 alkyl optionally substituted with one or more substituents independently selected from halogen and -OR 31 ; R 31 is independently selected at each occurrence from hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 3-12 carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -OSi(C 1 -C 6 alkyl) 3 , -CN, -NO 2 , -NH 2 , ═O, ═S, C 1-10 alkyl, -C 1-10 haloalkyl, -O-C 1-10 alkyl, -O-C 1-10 alkyl-OH, C 2-10 alkenyl, C 2-10 alkynyl, C 3-12 carbocycle, and 3-12 membered heterocycle; R ３２ represents, in each occurrence, hydrogen, as well as C １～１０ Alkyl, C ２～１０ Alkenyl, C ２～１０ Alkynyl, C ３～１０ Carbocycles and 3- to 10-membered heterocycles, each of which is independently selected from the group consisting of halogen, —OH, —CN, —NO ２ , -NH ２ , =O, =S, C １～１０ Alkyl, -C １～１０ Haloalkyl, —O—C １～１０ Alkyl, C ２～１０ Alkenyl, C ２～１０ Alkynyl, C ３～１０ optionally substituted with one or more substituents independently selected from: carbocycle, and 3- to 10-membered heterocycle; The substituents on V, in each occurrence, are Halogen, -OR ３０ , -N(R ３０ ) ２ , -SR ３０ , -C(O)R ３０ , -C(O)N(R ３０ ) ２ , -N(R ３０ ) C(O)R ３０ , -C(O)OR ３０ , -OC(O)R ３０ , -S(O)R ３０ , -S(O) ２ R ３０ , -P(O)(OR ３０ ) ２ , -OP(O)(OR ３０ ) ２ , -NO ２ , =S, =N(R ３０ ), and -CN, C １～１０ Alkyl, C ２～１０ Alkenyl, C ２～１０ Alkynyl, each of which is halogen, -OR ３０ , -SR ３０ , -N(R ３０ ) ２ , -C(O)R ３０ , -C(O)N(R ３０ ) ２ , -N(R ３０ ) C(O)R ３０ , -C(O)OR ３０ , -OC(O)R ３０ , -S(O)R ３０ , -S(O) ２ R ３０ , -P(O)(OR ３０ ) ２ , -OP(O)(OR ３０ ) ２ , -NO ２ , =O, =S, =N(R ３０ ), -CN,C ３～１０ optionally substituted with one or more substituents independently selected from carbocycle and 3- to 10-membered heterocycle; C ３～１０ Carbocycles and 3- to 10-membered heterocycles, each of which is independently selected from halogen, -OR ３０ , -SR ３０ , -N(R ３０ ) ２ , -C(O)R ３０ , -C(O)N(R ３０ ) ２ , -N(R ３０ ) C(O)R ３０ , -C(O)OR ３０ , -OC(O)R ３０ , -S(O)R ３０ , -S(O) ２ R ３０ , -P(O)(OR ３０ ) ２ , -OP(O)(OR ３０ ) ２ , -NO ２ , =O, =S, =N(R ３０ ), -CN,C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, and C ２～６ and optionally substituted with one or more substituents independently selected from alkynyl. are independently selected from 2. The compound or salt of claim 1, wherein R 1 is selected from -S(O) 2 OH and -S(O) 2 C 1-6 alkyl, said C 1-6 alkyl being optionally substituted with one or more substituents selected from halogen, -OH, -NO 2 , ═O, -O-C 1-6 alkyl.

3. The compound or salt of claim 2, wherein R 1 is selected from -S(O) 2 C 1-6 alkyl, said C 1-6 alkyl being optionally substituted with one or more substituents selected from halogen, -OH, -NO 2 , ═O, -O-C 1-6 alkyl.

4. The compound or salt of claim 3, wherein R 1 is selected from -S(O) 2 C 1-6 alkyl, said C 1-6 alkyl being unsubstituted.

5. -OL-R 1 is 【Chemistry 4】 2. The compound or salt of claim 1, selected from:

6. -OL-R 1 is 【Chemistry 5】 6. The compound or salt of claim 5, selected from:

7. The compound or salt of claim 1, wherein R 25 of R 4 is selected from hydrogen, optionally substituted C 1 -C 6 alkyl, -D-(CH 2 -CH 2 -G) y -V, optionally substituted 3-10 membered heterocycle, and optionally substituted C 3-10 carbocycle.

8. The compound or salt of claim 7, wherein the optionally substituted C 1 -C 6 alkyl of R 25 is substituted with one or more substituents selected from a C 3-20 carbocycle, -OH and -O-C 1-10 alkyl.

9. The compound or salt of claim 8, wherein the optionally substituted C 1 -C 6 alkyl of R 25 is substituted with one or more substituents selected from -OH and -O-C 1-10 alkyl.

10. The compound or salt of claim 7, wherein D is -O-, G is -O-, y is 1 to 3, and V is selected from -C1 to C6 alkyl and hydrogen.

11. The compound or salt of claim 10, wherein R 25 is selected from hydrogen and -D-(CH 2 -CH 2 -G) y -V, where D is -O-, G is -O-, y is 1 to 3, and V is selected from -C 1 to C 6 alkyl and hydrogen.

12. The compound or salt of claim 1, wherein R' and R'' at each occurrence are independently selected from hydrogen.

13. The compound or salt of claim 1, wherein z is selected from 1, 2 and 3.

14. R 4 is 【Chemistry 6】 2. The compound or salt of claim 1, selected from:

15. R 4 is 【Chemistry 7】 2. The compound or salt of claim 1, selected from:

16. R 4 is 【Chemistry 8】 2. The compound or salt of claim 1, selected from:

17. R 4 is 【Chemistry 9】 2. The compound or salt of claim 1, selected from:

18. R 4 is 【Chemistry 10】 18. The compound or salt of claim 17, selected from:

19. The compound comprising: 【Chemistry 11-1】 【Chemistry 11-2】 【Chemistry 11-3】 or any one of pharma- ceutically acceptable salts thereof.

20. The compound of claim 1, 【Chemistry 12-1】 【Chemistry 12-2】 or any one of pharma- ceutically acceptable salts thereof.

21. The compound of claim 1, 【Chemistry 13】 2. The compound or salt of claim 1, which is:

22. The compound comprising: 【Chemistry 14】 2. The compound or salt of claim 1, which is:

23. The compound of claim 22, 【Chemistry 15】 2. The compound or salt of claim 1, which is:

24. The compound comprising: 【Chemistry 16】 2. The compound or salt of claim 1, which is:

25. The compound of claim 1, 【Chemistry 17】 2. The compound or salt of claim 1, which is:

26. The compound of claim 1, 【Chemistry 18】 2. The compound or salt of claim 1, which is:

27. The compound comprising: 【Chemistry 19】 2. The compound or salt of claim 1, which is:

28. A pharmaceutical composition comprising the compound or salt of claim 1 and a pharma- ceutically acceptable excipient.

29. A pharmaceutical composition as described in claim 28 for treating a subject having a chronic disease, characterized in that the subject would benefit from inhibition of mTORC1 activity.

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