HSD17B13 DICHLOROPHENOL INHIBITORS AND THEIR USES

Abstract

This document describes HSD17B13 inhibitors and pharmaceutical compositions comprising such inhibitors. The compounds and compositions in question are useful for the treatment of liver diseases, metabolic diseases, or cardiovascular diseases, such as NAFLD or NASH, or drug-induced liver injury (DILI).

Description

DICHLOROPHENOL HSD17B13 INHIBITORS AND USES THEREOF CROSS REFERENCE TO RELATED REQUESTS This application claims the benefit of US provisional application serial number 63 / 113,555 filed on November 13, 2020; US provisional application with serial number 63 / 113,557 filed on November 13, 2020; US provisional application with serial number 63 / 170,855 filed on April 5, 2021; and U.S. Provisional Application Serial No. 63 / 225,282 filed July 23, 2021, which are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION Nonalcoholic fatty liver diseases (NAFLD), including NASH (non-alcoholic steatohepatitis), are considered to be hepatic manifestations of metabolic syndrome and are characterized by the accumulation of triglycerides in the liver. liver of patients without a history of excessive alcohol consumption. Most patients with NAFLD are obese or morbidly obese and have concomitant insulin resistance. The incidence of NAFLD / NASH has increased rapidly worldwide in line with the increasing prevalence of obesity, and it is currently the most common chronic liver disease. NAFLD is classified into simple steatosis, where only hepatic steatosis is seen, and NASH, where intralobular inflammation and ballooning degeneration of hepatocytes are seen along with hepatic steatosis. The proportion of patients with NAFLD who have NASH is still unclear, but could range between 20 and 40%. NASH is a progressive disease and can lead to liver cirrhosis and hepatocellular carcinoma. Twenty percent of patients with NASH are reported to develop cirrhosis, and 30 to 40% of patients with cirrhosis from NASH experience liver-related death. Recently, NASH has become the third most common indication for liver transplantation in the United States. Currently, the main treatment for NAFLD / NASH is lifestyle modification through diet and exercise. However, drug therapy is indispensable because obese patients with NAFLD often have difficulty maintaining a better lifestyle. 17p-Hydroxysteroid dehydrogenases (HSD17B) comprise a large family of 15 members, some of which are involved in sex hormone metabolism. Some HSD17Bs enzymes also play a key role in cholesterol and fatty acid metabolism. A recent study showed that hydroxysteroid 17βdehydrogenase 13 (HSD17B13), an enzyme with unknown biological function, is a novel liver-specific lipid droplet (LD)-associated protein in oonRhn / cznz / a / υιλι mice and humans. HSD17B13 expression is markedly increased in patients and mice with nonalcoholic fatty liver disease (NAFLD). Hepatic overexpression of HSD17B13 promotes lipid accumulation in the liver. HSD17B13 may also have potential as a biomarker for chronic liver disease, such as alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD) (e.g. steatosis, nonalcoholic steatohepatitis (NASH) , NASHfibrosis or cirrhosis), steatohepatitis and liver cancer. BRIEF DESCRIPTION OF THE INVENTION Provided herein are methods, compounds and compositions useful for reducing the expression or activity of HSD17B13 in a subject in need thereof. Furthermore, provided herein are methods, compounds and compositions comprising specific inhibitors of HSD17B13, which may be useful in reducing the morbidity of HSD17B13-related diseases or conditions in a subject in need thereof. Such methods, compounds and compositions may be useful, for example, for treating, preventing, delaying or ameliorating liver disease, metabolic disease or cardiovascular disease. Described herein is a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers: each Z is independently N or GR1; each R1 are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; L is -O-, -C(=O)NR3-, -NR3C(=O)-, -C(=O)C(R4)2-, or -C(R4)2C(=O)-; R3 is hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; each R4 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; Ring A is a 3 to 12 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, N, P and B; each R5 is independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; or two R5s on the same atom join together to form an oxo; n is 0-6; RAes: (a) -C(=O)NR10R11; or (b) C4-C10 alkyl optionally substituted with one or more RAa; or (c) -(C(R12)2)pCYcloalkyl, -(C(R12)2)Pheterocycloalkyl, -(C(R12)2)Paryl, or (C(R12)2)pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally and independently substituted with one or more RAbs; R10 and R11 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl, C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, CiC10 heteroalkyl, C2-C10 alkenyl, C2-C10 alkynyl. , cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or Ci-C6 alkyl (heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a; each R10ais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, C1-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10b; or two R10a on the same atom join together to form an oxo; each R10bes independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R10ben the same atom join together to form an oxo; each RAason independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, oonRhn / cznz / a / υιλι C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C(=O)NRcRd, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAaon the same atom come together to form an oxo; each RAbson independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Oí-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Oí-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAben the same atom come together to form an oxo; each RAaais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; each R12 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Cs haloalkyl, Ci-Ce deuteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R12on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl are optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-Οθ haloalkyl, Οι-deuteroalkyl Οθ, or two R12on the adjacent carbon join together to form a cycloalkyl optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Οι-Οθ alkyl, Οι-haloalkyl Οθ, Οι-Οθ deuteroalkyl; p is 1-4; each Raes independently Ci-Οθ alkyl, Ci-Οθ haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Οθ aminoalkyl, Ci-Οθ heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl , cycloalkyl, heterocycloalkyl, aryl, heteroaryl, CiCetcycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or C1C6 alkyl (heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, oonRhn / cznz / a / υιλι halogen, -CN, -OH, -OCH3, -S( =O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3 )2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, CiCe alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, aminoalkyl CiCe, or Ci-Ce heteroalkyl; each Rbes independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2 alkynyl -Ce, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, CiCe alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, or Ci heteroalkyl -C3; and each Rcy Rd is independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, alkynyl C2-Ce, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroahlo); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3j-C(=O)OH, -C(=O)OCH3, CiCe alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, or Ci- heteroalkyl EC; or Rcy Rdse taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, OCH3, -S(=O)CH3j-S(=O)2CH3 , -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, N(CH3)2, -C(=O)CH3i-C (=O)OH, -C(=O)OCH3 Ci-C6 alkyl, Ci-C6 haloalkyl, CrCe deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, or CiC6 heteroalkyl; as long as the compound is not oonRhn / cznz / a / υιλι Λ / tZ / ZUZ Ó / UHUUOO Herein a compound of Formula (the), or one of its Λ / tz / zuz ó / unauoo pharmaceutically acceptable salts, solvates or stereoisomers: CL 'KJn Formula (la). Described herein is a compound of Formula (Ib), or one of its pharmaceutically acceptable salts, solvates or stereoisomers: Herein a compound of Formula (le), or one of its pharmaceutically acceptable salts, solvates or stereoisomers: Formula (le). Described herein is a compound of Formula (Id), or one of its pharmaceutically acceptable salts, solvates or stereoisomers: HO Cl oonRbn / cznz / a / υιλι Also described herein is a pharmaceutical composition comprising a compound described herein, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, and a pharmaceutically acceptable carrier. Also described herein is a method of treating a disease in a subject in need thereof, the method comprising administering a pharmaceutically effective amount of a compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, or a pharmaceutical composition described herein. In some embodiments of a method of treating a disease, the disease is a liver disease, a metabolic disease, or a cardiovascular disease. In some embodiments of a method of treating a disease, the disease is NAFLD. In some embodiments of a method of treating a disease, the disease is NASH. In some embodiments of a method of treating a disease, the disease is drug-induced liver injury (DILI). In some embodiments of a method of treating a disease, the disease is associated with HSD17B13. In some embodiments of a method of treating a disease, the disease is alcoholic liver disease. In some embodiments of a method of treating a disease, the disease is cirrhosis. In some embodiments of a method of treating a disease, the disease is decompensated portal hypertension. In some embodiments of a method of treating a disease, the disease is a cholestatic liver disease. INCORPORATION BY REFERENCE All publications, patents and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference. DETAILED DESCRIPTION OF THE INVENTION Definitions In the following description, certain specific details are set forth to provide a complete understanding of various modalities. However, one skilled in the art will understand that the invention can be practiced without these details. In other cases, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the modalities. Unless the context requires otherwise, throughout the specification and claims that follow, the word comprises and its variations, such as comprise and comprising should be interpreted in an open and inclusive sense, that is, as including, but not limited to. Furthermore, the headings provided herein are for convenience only and do not construe the scope or significance of the claimed invention. Reference throughout this specification to some modalities or a modality means that a particular feature, structure or characteristic described in relation to the modality is included in at least one modality. Therefore, the occurrences of phrases in one modality or in the modality in various places throughout this specification do not necessarily all refer to the same modality. Furthermore, particular features, structures or features may be combined in any suitable manner in one or more embodiments. Furthermore, as used in this specification and the accompanying claims, the singular forms a, an, and the include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally used in its sense that includes “and / or” unless the content clearly indicates otherwise. The following terms, as used in this document, have the following meanings, unless otherwise indicated: “oxo” refers to =0. “Carboxyl” refers to -COOH. “Alkyl” refers to a straight-chain or branched-chain saturated hydrocarbon monoradical having from one to about ten carbon atoms, more preferably from one to six carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl -3-butyl, 2,2-dimethyl-1 -propyl, 2-methyl-1 -pentyl, 3-methyl-1 -pentyl, 4-methyl-1 -pentyl, 2-methyl2-pentyl, 3-methyl-2 -pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1 -butyl, 3,3-dimethyl-1 -butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t- butyl, n-pentyl, isopentyl, neopentyl, tert-amyl, and hexyl, and longer alkyl groups, such as heptyl, octyl, and the like. Whenever it appears here, a numerical range such as “Ci-Ce alkyl” or “Ci-ealkyl”, means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms , 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some embodiments, the alkyl is a C1-10 alkyl. In some embodiments, the alkyl is a C1-6 alkyl. In some embodiments, the alkyl is a C1-5 alkyl. In some embodiments, the oonRhn / cznz / a / υιλι alkyl is a C1-4 alkyl. In some embodiments, the alkyl is a C1-3 alkyl. Unless otherwise specifically indicated in the specification, an alkyl group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkyl is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl is optionally substituted with halogen, -CN, -OH or -OMe. In some embodiments, the alkyl is optionally substituted with halogen. Alkenyl refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon double bonds and having two to about ten carbon atoms, more preferably two to about six carbon atoms. The group may be in ciso trans conformation on the double bond(s), and should be understood to include both isomers. Examples include, but are not limited to, ethenyl (-CH=CH2), 1-propende (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3butadienyl and the like. Whenever it appears here, a numerical range such as “C2Ce alkenyl” or “C2-6alkenyl” means that the alkenyl group can consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where a numerical range is not specified. Unless otherwise specifically indicated in the specification, an alkenyl group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkenyl is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or NO2. In some embodiments, the alkenyl is optionally substituted with halogen, -CN, -OH or -OMe. In some embodiments, the alkenyl is optionally substituted with halogen. Alkynyl refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon triple bonds and having two to about ten carbon atoms, more preferably two to about six carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl and the like. Whenever it appears here, a numerical range such as “C2-C6 alkynyl” or “C2-6alkynyl” means that the alkynyl group can consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where a numerical range is not specified. Unless otherwise specifically indicated in the specification, an alkynyl group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, oonRhn / cznz / a / υιλι cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkynyl is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or NO2. In some embodiments, the alkynyl is optionally substituted with halogen, -CN, -OH or OMe. In some embodiments, the alkynyl is optionally substituted with halogen. "Alkylene" refers to a linear or branched divalent hydrocarbon chain. Unless otherwise specifically indicated in the specification, an alkylene group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkylene is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or NO2. In some embodiments, the alkylene is optionally substituted with halogen, -CN, -OH or -OMe. In some embodiments, the alkylene is optionally substituted with halogen. “Alkoxy” refers to a radical of formula -OR, where Ra is an alkyl radical as defined. Unless otherwise specifically indicated in the specification, an alkoxy group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkoxy is optionally substituted with halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or NO2. In some embodiments, the alkoxy is optionally substituted with halogen, -CN, -OH or -OMe. In some embodiments, the alkoxy is optionally substituted with halogen. "Aryl" refers to a radical derived from a hydrocarbon ring system comprising 6 to 30 carbon atoms and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is linked through an aromatic ring atom) or bridged ring systems. . In some embodiments, the aril is a 6 to 10 membered aril. In some embodiments, the aryl is a 6-membered aryl (phenyl). Aryl radicals include, but are not limited to, aryl radicals derived from the hydrocarbon ring systems of anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene and triphenylene. Unless otherwise specifically indicated in the specification, an aryl may be optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl , heterocycloalkyl, heteroaryl, and the like. In some embodiments, the aryl is optionally substituted with halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. In some embodiments, the aryl oonRhn / cznz / a / υιλι is optionally substituted with halogen. Cycloalkyl refers to a partially or fully saturated monocyclic or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or heteroaryl ring, the cycloalkyl is linked through a non-aromatic ring atom) or bridged ring systems. In some embodiments, the cycloalkyl is completely saturated. Representative cycloalkyls include, but are not limited to, cycloalkyls having three to fifteen carbon atoms (C3-C15 cycloalkyl or C3-C15 cycloalkenyl), three to ten carbon atoms (C3-C10 cycloalkyl or C3-Ccycloalkenyl). C10), three to eight carbon atoms (C3-C8 cycloalkyl or Cs-Cs cycloalkenyl), three to six carbon atoms (C3-C6 cycloalkyl or Cs-Ce cycloalkenyl), three to five atoms of carbon (C3-C5 cycloalkyl or C3-C5 cycloalkenyl), or three to four carbon atoms (C3-C4 cycloalkyl or C3-C4 cycloalkenyl). In some embodiments, the cycloalkyl is a 3- to 10-membered cycloalkyl or a 3- to 10-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 3- to 6-membered cycloalkyl or a 3- to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl or a 5- to 6-membered cycloalkenyl. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cisdecalin, trans-decalin, bicyclo[2.1,1]hexane, bicyclo[2.2.1] heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane and bicyclo[3.3.2]decane, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Partially saturated cycloalkyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. Unless otherwise specifically indicated in the specification, a cycloalkyl is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -COOH, COOE, -CF3, -OH, -OMe, -NH2, or NO2. In some embodiments, a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. In some embodiments, the cycloalkyl is optionally substituted with halogen. “Halo” or “halogen” refers to bromine, chlorine, fluorine or iodine. In some embodiments, the halogen is fluorine or chlorine. In some embodiments, the halogen is fluorine. “Haloalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, for example, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1 ,2-difluoroethyl, 3bromo-2-fluoropropyl, 1,2-dibromoethyl and the like. “Hydroxyalkyl” refers to an alkyl radical, as defined above, that is oonRhn / cznz / a / υιλι substituted by one or more hydroxyls. In some embodiments, the alkyl is substituted with a hydroxyl. In some embodiments, the alkyl is substituted with one, two or three hydroxyls. Hydroxyalkyl include, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl. "Aminoalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with an amine. In some embodiments, the alkyl is substituted with one, two or three amines. Aminoalkyls include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl. "Deuteroalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more deuteriums. In some embodiments, the alkyl is substituted with a deuterium. In some embodiments, the alkyl is substituted with one, two or three deuterium. In some embodiments, the alkyl is substituted with one, two, three, four, five or six deuterium. Deuteroalkyls include, for example, CD3, CH2D, CHD2, CH2CD3, CD2CD3, CHDCD3, CH2CH2D, or CH2CHD2. In some embodiments, the deuteroalkyl is CD3. Heteroalkyl refers to an alkyl group wherein one or more alkyl skeletal atoms are selected from an atom other than carbon, e.g., oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus , or combinations thereof. A heteroalkyl is attached to the rest of the molecule on a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a Ci-Ceen heteroalkyl where the heteroalkyl consists of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen, nitrogen (e.g., -NH-, -N( alkyl)-), sulfur, phosphorus or combinations thereof where the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyl are, for example, -CH2OCH3, -CH2CH2OCH3, CH2CH2OCH2CH2OCH3, -CH(CH3)OCH3, -CH2NHCH3, -CH2N(CH3)2, -CH2CH2NHCH3, or CH2CH2N(CH3)2. Unless otherwise specifically indicated in the specification, a heteroalkyl is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, a heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, a heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroalkyl is optionally substituted with halogen. Heterocycloalkyl refers to a fully or partially saturated 3 to 24 membered ring radical comprising 2 to 23 carbon atoms and one to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur. In some embodiments, the heterocycloalkyl is completely saturated. In some embodiments, the oonRhn / cznz / a / υιλι heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocycloalkyl comprises one to three nitrogens. In some embodiments, the heterocycloalkyl comprises one or two nitrogens. In some embodiments, the heterocycloalkyl comprises a nitrogen. In some embodiments, the heterocycloalkyl comprises a nitrogen and an oxygen. Unless specifically stated otherwise in the specification, the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused ring systems (when fused with an aryl or heteroaryl ring, the heterocycloalkyl is linked through a non-aromatic ring atom) or bridged; and the nitrogen, carbon or sulfur atoms in the heterocycloalkyl radical may be optionally oxidized; the nitrogen atom may optionally be quaternized. Representative heterocycloalkyls include, but are not limited to, heterocycloalkyls having two to fifteen carbon atoms (C2-C15 heterocycloalkyl or C2-C15 heterocycloalkenyl), two to ten carbon atoms (C2C10 heterocycloalkyl or C2-C10 heterocycloalkenyl) , two to eight carbon atoms (C2-C8 heterocycloalkyl or C2-C8 heterocycloalkenyl), two to seven carbon atoms (C2-C7 heterocycloalkyl or C2-C7 heterocycloalkenyl), two to six carbon atoms (C2-C6 heterocycloalkyl or C2-C7 heterocycloalkenyl), two to five carbon atoms (C2-C5 heterocycloalkyl or C2-C5 heterocycloalkenyl), or two to four carbon atoms (C2-C4 heterocycloalkyl or C2-C4 heterocycloalkenyl). The examples of such radicals heterocycloquilo include, but are not limited to, azetidinil, oxetanyl, dioxolanil, tense [1,3] ditianil Hydroisoindolyl, 2-oxopiperazinilo, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidinyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tritianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxothiomorpholinyl, 1,1-dioxo-thiomorpholinyl , 1, 3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl and 2-oxo-1,3-dioxol-4-yl. The term heterocycloalkyl also includes all ring forms of carbohydrates, including, but not limited to, monosaccharides, disaccharides, and oligosaccharides. Unless otherwise noted, heterocycloalkyls have 2 to 10 carbons in the ring. It is understood that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including heteroatoms) that form the heterocycloalkyl (i.e., the skeletal atoms of the heterocycloalkyl ring). In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 4-membered 3-heterocycloalkenyl 3-heterocycloalkenyl heterocycloalkyl heterocycloalkyl heterocycloalkyl heterocycloalkyl. members. members. members. In In In In members. members. members. members. some some some some modalities, modalities, modalities, modalities, the the the the heterocycloalkyl heterocycloalkyl heterocycloalkyl heterocycloalkyl In some embodiments, the heterocycloalkyl In some embodiments, the heterocycloalkyl In some embodiments, the heterocycloalkyl In some embodiments, heterocycloalkyl is a 5- to 6-membered heterocycloalkenyl. Unless otherwise specifically indicated in the specification, a heterocycloalkyl may be optionally substituted as described below, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the heterocycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -COOH, COOE, -CF3, -OH, OMe, -NH2, or NO2. In some embodiments, the heterocycloalkyl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. In some embodiments, the heterocycloalkyl is optionally substituted with halogen. Heteroaryl refers to a 5- to 14-membered ring system radical comprising one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur, and at least one aromatic ring. . In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heteroaryl comprises one to three nitrogens. In some embodiments, the heteroaryl comprises one or two nitrogens. In some embodiments, the heteroaryl comprises a nitrogen. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is linked through an aromatic ring atom) or bridged ring systems. ; and the nitrogen, carbon or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may optionally be quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. In some embodiments, the heteroaryl is a 6-membered heteroaryl. In some embodiments, the heteroaryl is a 5-membered heteroaryl. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, bencindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, olyl, benzodioxinyl , benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, , indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopia ridazinyl, H- pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, , tetrazolyl, triazinyl and thiophenyl ( i.e. thienyl). Unless otherwise specifically indicated in the specification, a heteroaryl may be optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl , heterocycloalkyl, heteroaryl, and the like. In some embodiments, the heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or NO2. In some embodiments, the heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. In some embodiments, the heteroaryl is optionally substituted with halogen. The term “optional” or ‘Optionally’ means that the event or circumstance described below may or may not occur, and that the description includes instances where such event or circumstance occurs and instances where it does not occur. For example, optionally substituted alkyl means alkyl or substituted alkyl as defined above. Additionally, an optionally substituted group may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2FC3), monosubstituted (e.g., -CH2CH2F), or substituted at a level anywhere between fully substituted and monosubstituted ( for example, -CH2CHF2, CH2CF3, -CF2CH3, -CFHCHF2, etc.). Those skilled in the art will understand that, with respect to any group containing one or more substituents, such groups are not intended to introduce any substitution or pattern of substitution (for example, substituted alkyl includes optionally substituted cycloalkyl groups, which in turn are defined as including optionally substituted alkyl groups, potentially ad infinitum) that are spherically impractical and / or not synthetically feasible. Therefore, any substituent described should generally be understood as having a maximum molecular weight of about 1,000 daltons, and more typically, up to about 500 daltons. An effective amount or therapeutically effective amount refers to an amount of a compound administered to a mammal, either as a single dose or as part of a series of doses, that is effective to produce a desired therapeutic effect. The “treatment” of an individual (e.g., a mammal, such as a human) or a cell is any type of intervention used in an attempt to alter the natural course of the individual or cell. In some embodiments, the treatment includes administration of a pharmaceutical composition, subsequent to the onset of a pathological event or contact with an etiological agent and includes stabilization of the condition (e.g., the condition does not worsen) or alleviation of the condition. In some embodiments, the treatment also includes prophylactic treatment (e.g., administration of a composition described herein when an individual is suspected of suffering from liver disease, e.g., NAFLD). Synergy or synergize refers to an effect of a combination that is greater than the sum of the effects of each component alone at the same doses. “HSD17B13” means hydroxysteroid 17-beta dehydrogenase 13 and refers to any HSD17B13 nucleic acid. For example, in some embodiments, HSD17B13 includes a DNA sequence encoding HSD17B13, an RNA sequence transcribed from DNA encoding HSD17B13 (including genomic DNA comprising introns and exons). HSD17B13 may also refer to any amino acid sequence of HSD17B13 (may include secondary or tertiary structures of the protein molecule), encoded by a DNA sequence and / or an RNA sequence. The target can be referred to in upper or lower case. Compounds Disclosed herein are compounds of Formula (I), or one of their pharmaceutically acceptable salts, solvates or stereoisomers, useful in the treatment of liver diseases. In some embodiments, the liver disease is NAFLD. Described herein is a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers: oonRhn / cznz / a / υιλι each Z is independently N or CR1; each R1 are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; L is -O-, -C(=O)NR3-, -NR3C(=O)-, -C(=O)C(R4)2-, or -C(R4)2C(=O)-; R3 is hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; each R4 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; Ring A is a 3 to 12 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, N, P and B; each R5 is independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; or two R5s on the same atom join together to form an oxo; n is 0-6; RAes: (a) -C(=O)NR10R11; or (b) C4-C10 alkyl optionally substituted with one or more RAa; or (c) -(C(R12)2)pCYcloalkyl, -(C(R12)2)pheterocycloalkyl, -(C(R12)2)paryl, or (C(R12)2)pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally and independently substituted with one or more RAbs; R10 and R11 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl, C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, C1C10 heteroalkyl, C2-C10 alkenyl, C2-C10 alkynyl. , cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or Ci-C6 alkyl (heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a; each R10ais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Οι-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10b; or two R10a on the same atom join together to form an oxo; each R10bes independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, oonRhn / cznz / a / υιλι haloalkyl Oí-Ce, Ci-Ce deuteroalkyl, Oí-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Oí-Ce heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R10ben the same atom come together to form an oxo; each RAason independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAaon the same atom come together to form an oxo; each RAbson independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, C1-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAben the same atom come together to form an oxo; each RAaais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, C1-C6 hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; each R12 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, C1-C6 haloalkyl, Ci-Ce deuteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R12on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl are optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-deuteroalkyl Ce, or two R12on the adjacent carbon come together to form a cycloalkyl optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-haloalkyl Ce, Ci-Ce deuteroalkyl; p is 1-4; oonRhn / cznz / a / υιλι each Raes independently Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-C6 deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-alkenyl C6, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-Ceyaryl alkyl), or C1C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCq aminoalkyl, or Ci heteroalkyl -Cs; each Rbes independently hydrogen, Ci-Ce alkyl, O-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2 alkynyl -Ce, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroahlo); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1C& aminoalkyl, or Ci heteroalkyl -Cs; and each Rcy Rd is independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, alkynyl C2-Cs, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3j-C(=O)OH, -C(=O)OCH3, C1C3 alkyl, CrCe haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Ce aminoalkyl, or Ci-Cs heteroalkyl; or Rcy Rdse taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, OCH3, -S(=O)CH3, -S(=O) 2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, N(CH3)2, -C(=O)CH3i- C(=O)OH, -C(=O)OCH3, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, or C1C6 heteroalkyl; as long as the compound is not oonRbn / cznz / a / υιλι Λ / C / ZUZÓ / U4UUOO Λ / C / ZUZÓ / U4UUOO Described herein is a compound of formula (I) or one of its pharmaceutically acceptable salts, solvates or stereoisomers.: where: Formula (I), CL H.O. Ring B is Yes N oCR1; each Z is independently N or CR1; each R1 are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; L is -O-, -C(=O)NR3-, -NR3C(=O)-, -C(=O)C(R4)2-, or -C(R4)2C(=O)-; R3 is hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; each R4 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; Ring A is a 3 to 12 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, N, P and B; each R5 is independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; or two R5s on the same atom join together to form an oxo; n is 0-6; RAes: (a) -C(=O)NR10R11; or (b) C4-C10 alkyl optionally substituted with one or more RAa; or (c) -(C(R12)2)pC¡cloalkyl, -(C(R12)2)pheteroc¡cloalkyl, -(C(R12)2)paryl, or (C(R12)2)pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally and independently substituted with one or more RAbs; R10 and R11 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl, C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, C1C10 heteroalkyl, C2-C10 alkenyl, C2-C10 alkynyl. , cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or Ci-C6 alkyl (heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a; each R10ais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, C1-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10b; or two R10a on the same atom join together to form an oxo; each R10bes independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, oonRhn / cznz / a / υιλι haloalkyl Oí-Ce, deuteroalkyl of Ci-Ce, hydroxyalkyl of Ci-Ce, aminoalkyl of Ci-Ce, heteroalkyl of Oí-Ce, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R10ben the same atom come together to form an oxo; each RAason independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAaon the same atom come together to form an oxo; each RAbson independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAben the same atom come together to form an oxo; each RAaais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; each R12 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; or two R12on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl are optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-deuteroalkyl Ce, p is 1-4; each Raes independently Ci-Ce alkyl, Ci-Ce haloalkyl, C1-C6 deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl , cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1 alkyl oonRhn / cznz / a / υιλι Ce(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or CiC6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, CiCe alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiC& aminoalkyl, or Ci heteroalkyl -EC; each Rbes independently hydrogen, Ci-Cs alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2 alkynyl -C3, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3i-S( =O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O )CH3, -C(=O)OH, -C(=O)OCH3, CiCq alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, or Ci- heteroalkyl EC; and each Rcy Rd is independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, alkynyl C2-Ce, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, CiC& alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, or Ci heteroalkyl -EC; or Rcy Rdse taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, OCH3, -S(=O)CH3, -S(=O) 2CH3, -S(=O)2NH2i-S(=O)2NHCH3, -S(=O)2N(CH3)2, -nh2, -NHCH3, N(CH3)2, -C(=O)CH3, - C(=O)OH, -C(=O)OCH3, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, or CiC6 heteroalkyl; as long as the compound is not oonRhn / cznz / a / υιλι Λ / C / ZUZÓ / U4UUOO Λ / E / ZUZ or / UHyUOO Described herein is a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers: where: Formula (I), Ring B is Yes N oCR1; each Z is independently N or CR1; each R1 are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; L is -O-, -C(=O)NR3-, -C(=O)C(R4)2-, or -C(R4)2C(=O)-; R3 is hydrogen, Ci-Οβ alkyl, Ci-Οβ haloalkyl, or Ci-Ce deuteroalkyl; each R4 is independently hydrogen, deuterium, halogen, Οι-Οβ alkyl, Oí-Ce haloalkyl, or Ci-Οθ deuteroalkyl; Ring A is a 3 to 12 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, N, P and B; each R5 is independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; or two R5s on the same atom join together to form an oxo; n is 0-6; RAes: (a) -C(=O)NR10R11; or (b) C4-C10 alkyl optionally substituted with one or more RAa; or (c) -(C(R12)2)pC¡cloalkyl, -(C(R12)2)Pheteroc¡cloalkyl, -(C(R12)2)Paryl, or (C(R12)2)Pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally and independently substituted with one or more RAbs; R10 and R11 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl, C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, C1C10 heteroalkyl, C2-C10 alkenyl, C2-C10 alkynyl. , cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-Ce alkyl (aryl), or Ci-C6 alkyl (heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a; each R10ais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10b; or two R10a on the same atom join together to form an oxo; each R10bes independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, oonRhn / cznz / a / υιλι heteroalkyl Ci-C6, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R10ben the same atom join together to form an oxo; each RAason independently deuterium, halogen, -CN, -NO2, ΌΗ, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S( =O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS( =O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C(= O)NRcRd, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAaon the same atom come together to form an oxo; each RAbson independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, C1-C6 haloalkyl, Oí-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, C1-C6 heteroalkyl, C2-Ce alkenyl, C2 alkynyl -Ce, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAben the same atom come together to form an oxo; each RAaais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, C1-C6 haloalkyl, Ci-Οθ deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2 alkynyl -Ce, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; each R12 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, C1-C6 haloalkyl, Ci-Οθ deuteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R12on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl are optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-deuteroalkyl Ce, or two R12on the adjacent carbon come together to form a cycloalkyl optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-haloalkyl Οθ, Ci-Ce deuteroalkyl; p is 1-4; each Raes independently Ci-Ce alkyl, Ci-Ce haloalkyl, oonRbn / cznz / a / υιλι Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-alkenyl C6, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1Cetcycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or C1C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Ce aminoalkyl, or Ci heteroalkyl -Cs; each Rbes independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2 alkynyl -Ce, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Ce aminoalkyl, or Ci heteroalkyl -EC; and each Rcy Rd is independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, alkynyl C2-Ce, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3, -C(=O)OH, -C(=O)OCH3, C1Cq alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Ce aminoalkyl, or Ci heteroalkyl -EC; or Rcy Rdse taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, OCH3, -S(=O)CH3, -S(=O) 2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, N(CH3)2, -C(=O)CH3i- C(=O)OH, -C(=O)OCH3, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, or C1C6 heteroalkyl; as long as the compound is not oonRhn / cznz / a / υιλι ci Λ / tZ / ZUZ Ó / UHUUOO Described herein is a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers: each Z is independently N or GR1; each R1 are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, NRcRd, CrCe alkyl, CrCe haloalkyl, or Ci-Ce deuteroalkyl; L is -O-, -C(=O)NR3-, -C(=O)C(R4)2-, or -C(R4)2C(=O)-; R3 is hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; each R4 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Cs haloalkyl, or Ci-Ce deuteroalkyl; Ring A is a 3 to 12 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, N, P and B; each R5 is independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; or two R5s on the same atom join together to form an oxo; n is 0-6; RAes: (a) -C(=O)NR10R11; or (b) C4-C10 alkyl optionally substituted with one or more RAa; or (c) -(C(R12)2)pC¡cloalkyl, -(C(R12)2)pheterocycloalkyl, -(C(R12)2)paryl, or (C(R12)2)pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally and independently substituted with one or more RAbs; R10 and R11 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl, C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, C1 heteroalkyl. Cyo, C2-C10 alkenyl, C2-C10 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl) , or Ci-C6(heteroaryl)alkyl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a; each R10ais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Oí-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10b; or two R10a on the same atom join together to form an oxo; each R10bes independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or two R10ben the same atom join together to form an oxo; each RAason independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAaon the same atom come together to form an oxo; each RAbson independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, C1-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, C1-C6 heteroalkyl, C2-Ce alkenyl, C2 alkynyl -Ce, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAben the same atom come together to form an oxo; each RAaais independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S (=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS (=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C( =O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2 alkynyl -Ce, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; each R12 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-C3 haloalkyl, or Ci-Ce deuteroalkyl; or two R12on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl are optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, C1-C6 haloalkyl, Ci-deuteroalkyl Ce, p is 1-4; each Raes independently Ci-Ce alkyl, Ci-Ce haloalkyl, C1-C6 deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2-Ce alkynyl , cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1Ceicycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or C1C6 alkyl (heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(= O)CH3j-C(=O)OH, -C(=O)OCH3, C1Ce alkyl, CrCe haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Ce aminoalkyl, or Ci-Ce heteroalkyl; each Rbes independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, hydroxy Ci-Ce alkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2 alkynyl -C6, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2i-NHCH3, -N(CH3)2, -C(=O )CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Cq aminoalkyl, or Ci- heteroalkyl C3; and each Rcy Rd is independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, oonRhn / cznz / a / υιλι deuteroalkyl of Ci-Ce, hydroxyalkyl of Ci-Ce, aminoalkyl of Ci-Ce, heteroalkyl of Ci-Ce, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-Cetcycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl), or Ci-C6 alkyl C6(heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S (=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2i-C(=O )CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, or Ci-heteroalkyl Cs; oonRhn / cznz / a / υιλι or Rcy Rd are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, OCH3, -S(=O)CH3 , -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, N(CH3)2, - C(=O)CH3i-C(=O)OH, -C(=O)OCH3, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci- aminoalkyl Ce, or C1C6 heteroalkyl; as long as the compound is not In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound is not OH θ. In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound does not In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound Λ / tz / zuz ó / unauoo In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound is not H% hn^N'JhH°—\\ #—i or CL In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound is of Formula (la): In some embodiments of a compound of Formula (I) or (la), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Y is N. In some embodiments of a compound of Formula (I) or (la), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Y is CR1. In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound is of Formula (Ib): In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound is of Formula (le): In some embodiments of a compound of Formula (I) or (le), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, a Z is CR1 and a Z is N. In some embodiments of a compound of Formula (I) or (le), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each Z is CR1. In some embodiments of a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the compound is of Formula (Id): oonRhn / cznz / a / υιλι In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R1 is hydrogen, deuterium, halogen, Ci-Cs alkyl, Ci-Ce haloalkyl , or Ci-Ce deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R1 is hydrogen, deuterium, halogen or Ci-Ce alkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R1 is hydrogen, deuterium or Ci-Ce alkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R1 is hydrogen. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, L is -O-, -C(=O)NR3-, C(= O)C(R4)2-, or -C(R4)2C(=O)-. In some embodiments of a compound of Formula (I), (la)(Id), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, L is C(=O)C(R4)2- or -C(R4) 2C(=O)-. In some embodiments of a compound of Formula (I), (la)(Id), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, L is -O-. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, L is -NR3C(=O)- or -C(=O)NR3- . In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, L is -C(=O)NR3-. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R3 is hydrogen or Ci-Ce alkyl. In some embodiments of a compound of Formula (I ), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R3 is hydrogen. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is a 3 to 10 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, N, P and B. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, the Ring A is a 3 to 10 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S or N. In some embodiments of a compound of Formula (I), (la)-(ld), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, ring A is a 3 to 6 membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S or N. In some embodiments of a compound of formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, ring A is an 8 to 12 membered bicyclic ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, or N. In some embodiments of a compound of formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, ring A is an 8 to 10 bicyclic ring. members optionally comprising 1-4 heteroatoms selected from the group consisting of O, S or N. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its salts, solvates or stereoisomers pharmaceutically Acceptable, Ring A is phenyl or a 5- or 6-membered heteroaryl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is a 5-membered heteroaryl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is a 6-membered heteroaryl. In some embodiments of a compound of formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, ring A is thiophene, tlazol, isothiazole, oxazole, isoxazole, phenyl, pyridine or pyrimidine. In some embodiments of a compound of formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, ring A is thiazole, isothiazole, oxazole, isoxazole, phenyl, pyridine or pyrimidine. In some embodiments of a compound of formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, ring A is thiophene, oxazole, isoxazole, phenyl, pyridine or pyrimidine. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is oxazole, isoxazole, phenyl, pyridine or pyrimidine. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is not thiophene. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is neither thiazole nor isothiazole. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is not a thiazole. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is not isothiazole. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or oonRhn / cznz / a / υιλι stereoisomers, Ring A is thiophene. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is tlazol or isothiazole. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is oxazole or isoxazole. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is phenyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is pyridine.In some embodiments of a compound of Formula (I), (la)(Id), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, Ring A is dihydroquinazoline, isoindoline or 2,3-dihydrobenzooxazepine. In some embodiments of a compound of Formula (I), (la)-(ld), or a salt thereof, is 0-4 and n” is 0-2. In some embodiments of a compound of Formula (I), (la)-(ld), or a salt thereof, In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, is In some embodiments of a compound of Formula (I), (la)-(ld), or a salt thereof, oonAhn / cznz / a / υιλι pharmaceutically acceptable solvates or stereoisomers,(r5)es r5c; where R5a, R5b, R5c and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-deuteroalkyl EC. In some embodiments of a compound of Formula (I), (la)-(ld), or a salt thereof, pharmaceutically acceptable solvates or stereoisomers, (R5)nes ; where R5a, R5b and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R5a is deuterium, halogen, -CN, -OH, -ORa, -SH, - SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5b, R5c, and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R5a is deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5b, R5c, and R5d are independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or CiC6 deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, wherein R5bes deuterium, halogen, -CN, -OH, -ORa, -NRcRd , Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5a, R5c, and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -SH, -SRa, -ORa, -NRcRd, CrCe alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, wherein R5bes deuterium, halogen, Οι-Οβ alkyl, Οι-Οβ haloalkyl , or Ci-Ce deuteroalkyl; and R5a, R5c, and R5d are independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or CrCe deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, wherein R5ces deuterium, halogen, -CN, -OH, -ORa, -NRcRd , Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5a, r5c, and p¡5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl . In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, wherein R5ces deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl , or Ci-Ce deuteroalkyl; and R5a, R5b, and R5d are independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, where R5 is deuterium, halogen, -CN, -OH, -ORa, -NRcRd , Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5a, R5b, and R5c are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or CrCe deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, wherein R5 is deuterium, halogen, CrCe alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5a, R5b, and R5c are independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or CrCe deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, wherein R5ces deuterium, halogen, -CN, -OH, -ORa, -NRcRd , Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; R5des deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or CrCe deuteroalkyl;, R5a, and R5b are independently hydrogen, deuterium, halogen, CN, -OH , -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, CrCe haloalkyl, or CrCe deuteroalkyl In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, wherein R5 is deuterium, halogen, C1-C5 alkyl, CrCe haloalkyl, or CrCe deuteroalkyl; R5des deuterium, halogen, CrCe alkyl, CrCe haloalkyl, or Ci-Ce deuteroalkyl;, R5a, and R5b are independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or oonRhn / cznz / a / υιλι deuteroalkyl of Οι-Οθ. In some embodiments of a compound of Formula (I), (la)-(ld), or a salt thereof, or onRhn / cznz / a / υιλι pharmaceutically acceptable solvates or stereoisomers, . In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R5 is independently hydrogen, deuterium, halogen, Οι-Οθ alkyl, Οι haloalkyl -Οθ, or CiC6 deuteroalkyl; or two R5s on the same atom are taken together to form an oxo. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R5 is independently hydrogen, deuterium, halogen or Ci-Οθ alkyl; or two R5s on the same atom join together to form an oxo. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R5 is independently hydrogen, halogen or Οι-Οθ alkyl; or two R5s on the same atom join together to form an oxo. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R5 is independently hydrogen, deuterium, halogen, Οι-Οθ alkyl, Οι haloalkyl -Οθ, or Οι-Οθ deuteroalkyl; or two R5s on the same atom join together to form an oxo. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R5 is independently hydrogen, Ci-Οθ alkyl, Ci-Οθ haloalkyl, or Οι-Οθ deuteroalkyl; or two R5s on the same atom join together to form an oxo. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 0-5. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 0-4. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 0-3. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 0-2. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 0 or 1. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 0. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its salts, pharmaceutically acceptable solvates or stereoisomers, n is 1. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 2. In some embodiments of a compound of Formula (I), (la)-(ld), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, n is 3. In some embodiments of a compound of Formula (I), (la)-(ld ), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 4. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 5. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n is 6. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n' is 0-3. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n' is 0-2. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n' is 0 or 1. In some embodiments of a compound of Formula (I) , (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n' is 0. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n' is 1. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n' is 2. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n' is 3. In some embodiments of a compound of Formula (I), ( la)-(ld), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, n' is 4. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n" is 0 or 1. In some embodiments of a compound of Formula (I) , (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n” is 0. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, n” oonRhn / cznz / a / υιλι is 1. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers acceptable, n” is 2. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, RA is -C(=O)NR10R11. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R11 is hydrogen or Ci-Ce alkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R11 is hydrogen. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R10 is C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl. , C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, C1-C10 heteroalkyl, Ci-C6 alkyl(cycloalkyl), Ci-C6 alkyl(heterocycloalkyl), Ci-C6 alkyl(aryl) or Ci-C alkyl C6(heteroaryl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R10 is C1-C10 alkyl optionally substituted with one or more R10a. In some embodiments of a compound of formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R10 is Ci-C6 alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl) , Ci-C6(aryl)alkyl, or Ci-C6(heteroaryl)alkyl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a. In some embodiments of a compound of formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R10 is Ci-Ce alkyl (aryl) or Ci-C6 alkyl (heteroaryl) ; wherein each alkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, R10 is Ci-C6 alkyl (aryl) wherein the aryl is optionally substituted with one or more R10a. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R10a is independently deuterium, halogen, -CN, -OH, -ORa, -NRcRd , -C(=O)Ra, -C(=O)Ob, -C(=O)NRcRd, C1C& alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Ce aminoalkyl , Ci-Ce heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10b. In some embodiments of a compound of Formula (I), (la)(Id), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R10aoonRhn / cznz / a / υιλι is independently deuterium, halogen, -CN, -OH , -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, or Ci-Ce heteroalkyl; wherein each alkyl is optionally and independently substituted with one or more R10b. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R10a is independently deuterium, halogen, -OH, -ORa, Ci-Ce alkyl , Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; wherein each alkyl is optionally and independently substituted with one or more R10b. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R10a is independently deuterium, halogen, -OH, -ORa, Ci-Ce alkyl , Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R10a is independently deuterium, halogen, -ORa, Ci-Ce alkyl, or haloalkyl by Ci-Ce. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, RA is C4-C10 alkyl optionally substituted with one or more RAa. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each RAa is independently deuterium, halogen, -CN, -OH, -ORa, -NRcRd , -C(=O)Ra, -C(=O)Ob, -C(=O)NRcRd, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAaon the same atom come together to form an oxo. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each RAa is independently deuterium, halogen, -CN, -OH, -ORa, -NRcRd , cycloalkyl or heterocycloalkyl; wherein each cycloalkyl and heterocycloalkyl is optionally and independently substituted with one or more RAaa. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each RAa is independently deuterium, halogen, -CN, -OH, -ORa, or - NRcRd. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, RA is -(C(R12)2)Pcycloalkyl, (C(R12)2) pheterocycloalkyl, -(C(R12)2)Paryl, or -(C(R12)2)Pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally and independently substituted with one or more RAbs. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, RA is -(C(R12)2)Paryl or (C(R12)2) Pheteroahlo; wherein the aryl and heteroaryl are optionally and independently substituted with one or more RAbs. In some embodiments of a compound of Formula (I), (la) oonRhn / cznz / a / υιλι (Id), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, RA is (C(R12)2)Paryl; wherein the aryl is optionally and independently substituted with one or more RAbs. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R12 is independently hydrogen, deuterium, halogen or Ci-Ce alkyl; or two R12s on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R12 is hydrogen or two R12 on the same carbon come together to form a cycloalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each R12 is hydrogen. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, two R12 on the same carbon come together to form a cycloalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, two R12on the adjacent carbon come together to form a cycloalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each RAbson independently deuterium, halogen, -CN, -OH, -ORa, -C (=O)Ra, -C(=O)Ob, -C(=O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci- aminoalkyl Ce, Ci-Ce heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAben the same atom are taken together to form an oxo. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each RAbson independently deuterium, halogen, -CN, -OH, -ORa, alkyl of Ci-Ce, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is optionally and independently substituted with one or more RAaa. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each RAbson independently deuterium, halogen, -CN, -OH, -ORa, alkyl of Ci-Ce, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; wherein each alkyl is optionally and independently substituted with one or more RAaa. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each RAaa is independently deuterium, halogen, -CN, -OH, -ORa, -C (=O)Ra, -C(=O)Ob, -C(=O)NRcRd, Ci-C6 alkyl, oonRhn / cznz / a / υιλι Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci hydroxyalkyl -Ce, Ci-C3 aminoalkyl, or Ci-Ce heteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, each Raaa is independently deuterium, halogen, -CN, -OH, -ORa, alkyl of Ci-Ce, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, p is 1-3. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, p is 1 or 2. In some embodiments of a compound of Formula (I), (la)-(ld), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, p is 1. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its salts, pharmaceutically acceptable solvates or stereoisomers, p is 2. In some embodiments of a compound of Formula (I), (la)-(ld), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, p is 3. In some embodiments of a compound described herein, each Ra is independently Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O )2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3j -C(=O)OH, -C(=O)OCH3, CiCe alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, Ci-Ce heteroalkyl. In some embodiments of a compound described herein, each Ra is independently CrCe alkyl, CrCe haloalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is optionally independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, S(=O)CH3, -S(=O)2CH3, -S (=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2i-C(=O)CH3, -C(= O)OH, -C(=O)OCH3, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl. In some embodiments of a compound described herein, each Ra is independently Ci-Ce alkyl, Ci-Ce haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of a compound described herein, each Ra is independently Ci-Ce alkyl or Ci-Ce haloalkyl. In some embodiments of a compound described herein, each Ra is independently alkyl of CiC6. oonRhn / cznz / a / υιλι In some embodiments of a compound described herein, each Rbes independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, CiΟθ deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O )2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3 , -C(=O)OH, -C(=O)OCH3, CiC& alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, Ci-Ce heteroalkyl. In some embodiments of a compound described herein, each Rbes independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is optionally independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O)2CH3, - S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, NHCH3, -N(CH3)2, -C(=O)CH3, -C( =O)OH, -C(=O)OCH3, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl. In some embodiments of a compound described herein, each Rbes independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of a compound described herein, each Rbes independently hydrogen, Ci-Ce alkyl, or CiCe haloalkyl. In some embodiments of a compound described herein, each Rbes independently hydrogen or Ci-Ce alkyl. In some embodiments of a compound described herein, each R° and Rd are independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Cs heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O )2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3j -C(=O)OH, -C(=O)OCH3, CiCq alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, CiCe aminoalkyl, Ci-Ce heteroalkyl. In some embodiments of a compound described herein, each Rcy Rd is independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is optionally independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O)2CH3, - S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -nh2, -NHCH3, -N(CH3)2, -C(=O)CH3j-C( =O)OH, -C(=O)OCH3, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl. In some embodiments of a compound described herein, each Rcy Rd is oonRhn / cznz / a / υιλι independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of a compound described herein, each Rcy Rd is independently hydrogen, Ci-Ce alkyl or Ci-C6 haloalkyl. In some embodiments of a compound described herein, each Rcy Rd is independently hydrogen or Ci-Ce alkyl. In some embodiments of a compound described herein, Rcy Rd are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -NH2 , NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci- deuteroalkyl Ce, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, C1C6 heteroalkyl. In some embodiments of a compound described herein, each RA, RAa, RAb, R10, R10a, R11, Ra, Rb, Rc, Rd, and the heterocycloalkyl formed when Rcy Rd are taken together are independently substituted with one, two, three or four substituents as defined herein. In some embodiments of a compound described herein, each RA, RAa, RAb, R10, R10a, R11, Ra, Rb, Rc, Rd, and the heterocycloalkyl formed when Rcy Rd are taken together are independently substituted with one, two or three substituents as defined herein. In some embodiments of a compound described herein, each RA, RAa, RAb, R10, R10a, R11, Ra, Rb, Rc, Rd, and the heterocycloalkyl formed when Rcy Rd are taken together are independently substituted with one or two substituents. as defined in this document. In some embodiments of a compound described herein, each RA, RAa, RAb, R10, R10a, R11, Ra, Rb, Rc, Rd, and the heterocycloalkyl formed when Rcy Rd are taken together is independently substituted with a substituent as follows: defined in this document. Any combination of the groups described above for the various variables is considered here. Throughout the specification, the groups and substituents thereof are chosen by one skilled in the art to provide stable residues and compounds. Described herein is a compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates or stereoisomers, selected from a compound of Table 1. oonRhn / cznz / a / υιλι Table 1. Exemplary compounds Ex. Structure Name 1 0 A / Cl 0 HN γ^ΟΗ A J As Cl N-(3-benzyl-4-oxo-3,4dihydroquinazolin-5-yl)-3,5dichloro-4-hydroxybenzamide 2 F Fsj / F cA^nh O 0 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-(2-(trifluoromethoxy)benzyl)- 3,4-dihydroquinazo¡n-5yl)benzamide 3 / N. A cAA^nh 0 0 3,5-dichloro-N-(3(cyclopropylmethyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 4 Cl AA A NH h°aS ιγΓν 0 cA^A^ nh 0 0 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-((2-oxo-1,2-dihydropyridin-4¡l)methyl)-3,4-dihydroquinazolin5- l)benzamide 5 0 0 HN^^fCI crA? I 3,5-dichloro-4-hydroxy¡-N-(3-(2methoxybenzyl)-4-oxo-3,4dihydroquinazolin-5yl)benzamide 6 o A^\.CI O HN ^A A AA^N>f|] ^'A^0H f>AJ Cl F I F 3,5-dichloro-4-hydroxy-N-(4-oxo3-(4-(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5yl)benzamide 7 0 A / ? \ / Cl O HN A^A AA^N rA toh AA AA ci 3,5-dichloro-N-(3-(4fluorobenzyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 8 O A / >. ,CI 0 HN Y F AA^N Tii A*31-1 A AA AA ci 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-(4-(trifluoromethoxy)benzyl)- 3,4 -dihydroquinazolin-5yl)benzamide Ex. Structure Name 9 0 0 3,5-dichloro-N-(3-(2fluorobenzyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 10 H0A 0ΙΛγΗ 0 0 3,5-dichloro-4-hydrox ¡-N-(4-oxo3-(3-(trifluoromethoxy¡)benzyl)3,4-dihydroquinazol¡n-5yl)benzamide 11 γΟτΆ) Cl Y or 3,5-dichloro-4-hydrox ¡-N-(4-oxo3-(3-(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5yl)benzamide 12 0 A / ^ / Cl = O HN ]| xA5 Γ (S)-3,5-dichloro-N-(3-(1-(3fluorophenyl)ethyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 13 Z / =° t>Lo o^ J g O 3,5-dichloro-N-(3-((3-fluoropyridin-4-yl)methyl)-4-oxo3,4-dihydroquinazolin-5-yl)-4hydroxybenzamide 14 Cl ^ΥΝ^ι νΛ ηοΛ W ^s c|^^NH 0 0 N-(3-((1,3,4-thiadiazol-2-¡l)methyl)4-oxo-3,4-dihydroquinazolen-5yl)-3,5 -dichloro-4hydroxybenzamide 15 ¿Aó ClAAyNH O 0 3,5-dichloro-4-hydroxy¡-N-(3(oxazol-4-ylmethyl)-4-oxo-3,4dihydroquinazolin-5yl)benzamide 16 ci^^NH 0 0 3,5-dichloro-N-(3-(3fluorobenzyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 17 M^O ΛΑζνη o cK Y 0 3,5-dichloro-4-hydroxy¡- N-(4-oxo3-(pyridin-4-ylmethyl)-3,4dihydroquinazolin-5-yl)benzamide Ex. Structure Name 18 -W? cr Y F F 0 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-(2-(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5yl)benzamide 19 z t>L° o^5 § o 3 ,5-dichloro-4-hydroxy¡-N-(4-oxo3-((6-(trifluoromethyl)pyrídin-3¡l)methyl)-3,4-dihydroquinazo¡n5-¡ l)benzamide 20 -A Wf c|A^nh 0 ¿> 0 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-(1 -phenylcyclopropyl)-3,4dihydroquinazolin-5yl)benzamide 21 cr γ or 3,5-dichloro-N-(3-(1-(2fluorophenyl)cyclopropyl)-4-oxo3,4-dihydroquinazolin-5-yl)-4hydroxybenzamide 22 cr n and 0 4,6-dichloro-N -(3-(3fluorobenzyl)-4-oxo-3,4dihydroquinazolin-5-¡l)-5hydroxypicolinamide 23 F-xj / F γγυο ciA^ynh 0 0 4,6-dichloro-5-hydroxy¡-N-(4 -oxo3-(2-(trifluoromethox¡)benzyl)3,4-dihydroquinazo¡n-5¡l)picol¡namide 24 HO k zCI c'xT °T-NH 0 NJHX^[íí:rX'¡l Vs HfA ^ 4-(3,5-dichloro-4hydroxybenzamide)-N-(2fluorobenzyl)thiazole-5carboxamide oonRhn / cznz / a / υιλι Ex. Structure Name 25 Cl odL^ci n^NH / / 1 H T f Y FY F 4-(3,5-dichloro-4hydroxybenzamide)-N-(2(trifluoromethyl)phenethyl)thiazole-5carboxamide 26 I O O rv o = / \I O 4-(3,5-dichloro-4hydroxybenzamido)-N-(2(trifluoromethyl)benzyl)thiazole-5carboxamide 27 Cl L Cl K, NH N-- / < <X N JO S'jT 0 Fv ° pY F 4-(3,5-dichloro-4h¡droxybenzamido)-N-(2(trifluoromethoxy)benzyl)thiazole-5carboxamide 28 HO X O αχΧ 0-¼ i__ %u YO F F 4-(3, 5-dichloro-4hydroxybenzamido)-N-(2,4difluorobenzyl)thiazole-5carboxamide 29 yd° 1 o— oZ ° \\ / > I ~ 4-(3,5-dichloro-4hydroxybenzamido)-N-(1 - (4fluorophenyl)cyclopropyl)thiazole-5carboxamide oonRhn / cznz / a / υιλι Ex. Structure Name 30 Cl \oh oJ^Al M / NH J f H fX^F o 4-(3,5-dichloro-4hydroxybenzam¡do)-N-((4,4difluorocyclohex¡l)met¡l)t azole-5carboxamide 31 HO k -Xa o aa o o T 5-(3,5-dichloro-4hydroxybenzamido)-N-(2(trifluoromethoxy)benzyl)thiazole-4carboxamide 33 HO k xCI c'kJ s. sh^A^A \=N H A J F 5-(3,5-dichloro-4hydroxybenzamide)-N-(2fluorobenzyl)thiazole-4carboxamide 34 Cl i°h oA^Aci Q ZNH / Vx. O 5-(3,5-dichloro-4h¡droxybenzamido)-N-(3fluorobenzyl)thiazole-4carboxamide 35 Cl xA^0H ΓΙ ογ^'ει NH ζίζ^θ o ^0AJ! 3-(3,5-dichloro-4hydroxybenzamide)-N-(2methoxyphenethyl)thiophene-2carboxamide oonRhn / cznz / a / υιλι Ex. Structure Name 36 0 / O. A ,CI lT ° HN ¡I XXdh A-V ci 3,5-dichloro-4-hydroxy¡-N-(3-(2methoxyphenethyl)-4-oxo-3,4dihydroquinazolin-5yl)benzamide 37 Cl ΗθΑΐ i Aa Cl NH . . ch-Ají n carboxamide 38 Cl '.OH OyXAci F <= / NH AF ο^χ Π F CIAAJ, / J I u 5-chloro-2-(3,5-dichloro-4hydroxybenzamido)-N-(2(trifluoromethox¡)phenet l)thiophene3-carboxamide 39 cAA^nh or 0 N-(3-((1,3,4-thiadiazol-2-yl)methyl)4-oxo-3,4-dihydroquinazolin-5yl )-3,5-dichloro-4hydroxybenzamide 40 o O / =\ η H h / \1 ^- Zx Z=° 3 o 4,6-dichloro-5-hydroxy¡-N-(4-oxo3-(3- (trifluoromethyl)benzyl)-3,4dihydroquinazolin-5¡l)picol¡namide 41 0 CI\^N^ JL ψ Y NH 0 Hcry ci ü A A ü A N 4,6-dichloro-N-{3-[(1S) -1-(3fluorophenyl)ethyl]-4-oxo-3,4dihydroquinazolin-5-yl}-5hydroxypyridine-2-carboxamide 42 0 VAh o h° τ ΑΑύχ ci ü Λ A ü A N F 4,6-dichloro-N-{3 -[(4fluorophenyl)methyl]-4-oxo-3,4dihydroquinazolin-5-yl}-5hydroxypyridine-2-carboxamide 43 o Cl\ A Αχ 4,6-dichloro-5-hydroxy¡-N-(4-oxo3- (2-(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5¡l)picolinam¡de Ex. Structure Name 44 o V / - o ncr'Y N F ~^ 4,6-dichloro-N-(3-(2fluorobenzyl)-4-oxo-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide 45 OH Ci^xL ^CI O^'NH 0 3,5-dichloro-4-hydroxy¡-N-(3-(4-(4methylpiperazin-1 -i l)benzyl)-4oxo-3,4-dih¡droquinazolín- 5yl)benzamide 47 OH CI\J\.CI tj O^NH 0 Ξ ¿Ó^O x / ' N v / (R)-3,5-dichloro-N-(3-(1-(3fluorophenyl)ethyl) -4-oxo-3,4dihydroquinazolin-5-¡l)-4hydroxybenzamide 48 OH O^NH 0 or 3,5-dichloro-A / -(3-(3cyanobenzyl)-4-oxo-3,4dihydroquinazolin-5-¡ l)-4hydroxybenzamide 49 o_ o—<^~^z n> \_ / I Z. )=O 3 O / o 4,6-dichloro-5-hydroxy- / V-(4-oxo3-(3- (trifluoromethoxy)benzyl)3,4-dihydroquinazolin-5yl)picolinamide 50 0 HO iXi'Xl CF 4,6-dichloro-5-hydroxy¡- / \ / -(4-oxo3-(4-(trifluoromethoxy )benz¡l)3,4-dihydroquinazo¡n-5¡l)picol¡namide 51 o O / = / / ^X 1 Λ / =° x,? 3,5-dichloro-4-hydroxy¡- / V-(3-(2(methylsulfon¡l)benzyl)-4-oxo-3,4dihydroquinazolin-5yl)benzamide. Ex. Structure Name 52 o C'1VNH 0 HO τ Cl Λ / -(3-((1 -(tert-butyl)-l Hpyrazol-3-yl)methyl)-4-oxo-3,4dihydroquinazolin-5 -yl)-3,5dichloro-4-hydroxybenzamide 53 o_ o— fyz° \__ / I z 7=° 'tí 3,5-dichloro-A / -(3-(2cyanobenzyl)-4-oxo-3,4dih ¡droquinazolin-5-yl)-4hydroxybenzamide 54 f2hc,0AJ o ^NH 3,5-dichloro-A / -[4-({[2- (difluoromethox¡)phenyl]methyl}amin o)quinazolin-5 -yl]-4- hydroxybenzamide 56 o γ ηρ^ΝΗ o H0 Γϊ Cl uu 1N> \ 3,5-dichloro-4-h hydroxy-A / -{3-[( 1 methyl-1 H-pyrazole-3- il)met¡l]-4oxo-3,4-dihydroqu¡nazol¡n-5¡IJbenzamide 57 OH ci^X^ci VJ O^NH 0 I 3,5-dichloro-A / -(3-(3, 3dimethylbut¡l)-4-oxo-3,4dihydroquinazolin-5-¡l)-4hydroxybenzamide 58 OH ClxJ^CI vj O^NH 0 Ho^a 3,5-dichloro-4-hydroxy¡- / \ / -(3 -(4-(2hydroxyethoxy¡)benz¡l)-4-oxo-3,4dihydroquinazolin-5- yl)benzamide 59 OH CixU^.C! Ο^ΉΗ 0 00'0., II 0 3,5-dichloro-4-hydroxy¡- / \ / -(3-(4(methylsulfonyl)benzyl)-4-oxo-3,4dihydroquinazoline-5- ¡ l)benzamide Ex. Structure Name 60 OH O^NH 0 . óóX 3,5-dichloro-4-hydroxy¡- / \ / -(3-(3(methylsulfonyl)benzyl)-4-oxo-3,4dihydroquinazolin-5yl)benzamide. 61 0 0ΙΎΝΎ^νη ° i 4,6-dichloro-N-(3-(3,3dimethylbutíl)-4-oxo-3,4dihydroquinazolin-5-íl)-5hydroxypicolinamide 62 o CK .N . A X 5-¡l)-4,6dichloro-5-hydroxypicolinamide 63 w A v° 3 i—Z. ' Oll o 3,5-dichloro-N-(3-(4-(1,1-dioxydotíomorpholino)benzyl)-4oxo-3,4-dihydroquinazolin-5-íl)4-hydroxybenzamide 64 OH Cix / L'CI A FA ONH O 3 O orib 3,5-dichloro-4-hydroxy¡-N-(2-methyl4-oxo-3-(2- (trifluoromethoxy¡)benzyl)-3,4dihydroquinazoline -5-yl)benzamide 65 Cl O HO. A nh 0 A^. and A. A x Cl n YV CF3 h Ί j Η J 2,4-dichloro-3-hydroxy-N-(4-oxo3-(3-(trifluoromethoxy)benzyl)3,4-dihydroquinazole ¡n-5yl)benzamide 66 0 CI1VNH ° ϊ H0^'i ci ÓAN2 M 4,6-dichloro-N-(3-(2cyanobenzyl)-4-oxo-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide 67 O ck A -hydroxy¡benzamide Ex. Structure Name 68 OH ci^X^ci Ο^ΉΗ 0 rA-^N^^CF3 Ll j Xj '''- N 3-chloro-5-cyano-4-hydroxy¡-N-(4oxo-3- (3-(trifluoromethyl)benzyl)3,4-dihydroquinazolin-5yl)benzamide 69 0 CK / ΪΧ. JL FoC. Yózxnh o 3 o Hcrv rí / u^N' / ^Tij ¿ U H u 3-(3,5-dichloro-4h¡droxybenzamido)-N-(2(trifluoromethoxy)benzyl)p¡choline measure 70 OH CI^Á^CI 1 XX CF 0 NH o o (tx\ ^-^N^CFs 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-(2-(trifluoromethoxy)benzyl) -2(trifluoromethyl)-3,4dihydroquinazolin-5yl)benzamide 71 OH d^J-xX! )carbamoyl)pheníl)-4hydroxybenzamide 72 O ck A Π ΪΗ u -ó· ¿ú|j 4,6-dichloro-N-(3-(1-(2-fluorophenyl)cyclopropíl)-4-oxo3 ,4-dihydroquinazolin-5-yl)-5hydroxypicolinamide 73 Cl / L,OH ojQ HN U °'CF3 3-(3,5-dichloro-4hydroxybenzamido)-N-(2(trifluoromethoxy¡)benzyl )¡son¡cot¡ namide 74 0 । O HN'X^Y'CI XXr O N cf3 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-(1-(2- (trifluoromethoxy)phen¡ l)ethyl)-3,4dihydroquinazolin-5-yl)benzamide oonRhn / cznz / a / υιλι Ex. Structure Name 75 OH Clx / L / CI [ΓΎ Ο^ΉΗ 0 CF3 N 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-((3-(trifluoromethyl)pyri¡ d¡n-2¡l)methyl)-3,4-dih¡droquinazolin5-¡l)benzamide 76 O ci^Znh 0 η°^γ ΛΛ^ Cl N'n' f A 3,5-dichloro-N- (3-((1-(2fluorophenyl)-1 H-pyrazol-3yl)methyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 77 0 ci^Anh oCl n'n A 3,5-dichloro -4-hydroxy¡-N-(4-oxo3-((1 -phenyl-1 H-pyrazol-3-yl)methyl)3,4-d¡hydroquinazolin-5yl)benzamide 78 OH ClxJ^CI 0 4,6-dichloro-5-hydroxy¡-N-(3-(2(methylsulfonyl)benzyl)-4-oxo-3,4dihydroquinazolin-5yl)picolinamide 80 0 CK A γγ NH ° HO^f N N 3, 5-dichloro-4-hydroxy-N-(4-oxo3-(pyridin-3-ylmethyl)-3,4dihydroquinazolin-5yl)benzamide 81 OH CI^4^,CI •í#k F,C. ONH 0 3 0 ÓÓXÓ ΎΝ Cl 3,5-dichloro-N-(8-chloro-4-oxo-3(2-(trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide oonRhn / cznz / a / υιλι Ex. Structure Name 82 OH Ο^ΉΗ O CF3 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-((2-(trifluoromethyl)pyr¡din-3¡l) methyl)-3,4-dihydroquinazolin5-¡l)benzamide 83 H0¿X “AT 0 0 3,5-dichloro-N-(3-(2-(1,1- dioxidothiomorphol¡no)benz¡ l)-4oxo-3,4-dihydroquinazolin-5-yl)4-hydroxybenzamide 84 OH ΟΙ,Α,ΟΙ I 0 0^ NH O N ¿A'ó 3,5-dichloro-4-hydroxy¡-N-(3 -(2morpholinobenzyl)-4-oxo-3,4dihydroquinazolin-5yl)benzamide 85 0 CK A ,cf3 p^|| NH O O 3 ho^y r ¿ U H u ,O ''Ά I 3,5-dichloro-N-(4-(2(dimethylamino)ethoxy¡)-2-((2(trifluoromelox¡)benc¡ l)carbamoyl)phenyl)-4-hydroxy¡benzamide 86 0 F3% O HNAf^fCI Φ«φΓΗ or ΌΗ 3,5-dichloro-4-hydroxy¡-N-(4-(2hydroxyethoxy¡)-2 -((2- (trifluoromethox¡)benz¡l)carbamo ¡l)phenyl)benzamide 87 OH οι^Α^,ο T¥ Ο^ΉΗ o óóo ^ N O N cf3 3,5-dichloro-4-hydroxy¡-N -(4-oxo3-((2-(tnfluoromethoxy¡)pyrídin-3yl)methyl)-3,4-dihydroqu¡nazol¡n5-¡l)benzamide oonRhn / cznz / a / υιλι Ex. Structure Name 88 OH CI^Y / CI TQT O^NH O γ / χ> I cf3 3,5-dichloro-4-hydroxy-N-(8-met¡l4-oxo-3-(2- (trifluoromethox¡)benzyl)-3,4dihydroquinazolin-5-yl)benzamide 89 OH Cl^ / Lxi and f3c. γι5> 3,5-dichloro-N-(2,8-dimethyl-4oxo-3-(2- (trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5-íl)-4hydroxybenzamide 90 OH CixJ^CI Y Y N .Y O^'NH O Cl cf3 4,6-dichloro-N-(8-chloro-4-oxo-3(2-(trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide 91 OH ci^Y,c| Y Y .Y f3cl Y~i 4,6-dichloro-5-hydroxy¡-N-(8-methyl4-oxo-3-(2- (trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5- ¡l)picolinamide 92 OH ci^Y^ci vj .Y F.C, O^NH O 3 O 3,5-dichloro-4-hydroxy-N-(4-oxo3-(2-(trifluoromethoxy)benzyl)3,4-dihydropyrido[2,3d ]p¡r¡m¡d¡n-5-il)benzam¡da oonRhn / cznz / a / υιλι Ex. Structure Name 93 OH Á F3C~~O O^NH 0 ΓΥγ V / N'XD 1 3,5-dichloro-4-hydroxy-N-(1 -methyl2,4-dioxo-3-(2- (trifluoromethoxy) benzyl)-1,2,3,4tetrahydroquinazolin-5-yl)benzamide 94 OH CI-^ / Lxi ιγύ 'b'x y C F 9 CT NH O ψ O J ΎυΑ 3,5-dichloro-4-hydroxy¡- N-(6-methyl4-oxo-3-(2-(trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5-yl)benzamide 95 or ClxYí>úr'NH O OCF3 «θ'τ (\VyS Cl YÁA M H 3,5-dichloro-N-(2,4-dioxo-3-(2(trifluoromethoxy)benzyl)-1,2,3,4tetrahydropyr¡do[2,3-d]pyr¡ mid¡n5-¡l)-4-hydroxybenzamide 96 OH ci^A^ci Ο*ΉΗ 0 O'^^ ÓÓCÚ 3,5-dichloro-4-h¡drox¡-N-(2-met¡l4 -oxo-3-(2- (trifluoromethoxy¡)benzyl)-3,4dihydropyrido[2,3-d]pyrimidin-5- ¡I) benzamide 97 O O HN--\_ CFÓ3 MCI ^I\T sC| / OH N-(3-benzyl-4-oxo-3,4dihydrotiene[2,3-d]pyrimidin-5yl)-3,5-dichloro-4hydroxybenzamide 98 0 O HN-A_. OCNód vT1 OI N-(3-benzyl-4-oxo-3,4dihydrothieno[2,3-d]pyrimidin-5¡l)-4,6-didoro-5hydroxypicolinamide 99 P > ονΓ° — T o N-(5 -benzyl-1 -methyl-4-oxo-4,5dihydro-1 H-pyrazolo[3,4d]pyrimidin-3-yl)-3,5-dichloro-4hydroxybenzamide Ex. Structure Name 100 OH cixA-Gi TJ O^NH 0 N 3,5-dichloro-4-hydroxy-N-(4-oxo3-(pyrazolo[1,5-a]pyridi n-3¡lmethyl)-3 ,4-dihydroquinazolin-5yl)benzamide 101 OH d^A.01 trifluoromethyl)-3,4dihydroquinazolin-5¡l)picolinam¡da 102 H L - -1 :=l ϊι : T c ··· •j- ·: i L . / Y ... CX.J u trans racemic Rac- 3,5-dichloro-4-hldroxy¡-N-(4oxo-3-((1 R,2S)-2phenylcyclopropyl)-3,4dihydroquinazolin-5yl)benzamide 103 YY ΥΥ O\ 1 Ω 3,5-dichloro-4 -hldroxy-N-(4-oxo3-(2-(trifluoromethoxy¡)benzyl)3,4-dihydrothieno[2,3-d]pyrimidin5-¡l)benzamide 104 O T \ .o £X_ z <-> Y 4,6-dichloro-5-hydroxy-N-(4-oxo3-(2-(trifluoromethoxy)benzyl)3,4-dihydrothieno[2,3-d]pyrimidin5-yl)picolinamide 105 \ O ci\ / ^ A n3 YV^NH O Y Y / rc 3,5-dichloro-4-hydroxy¡- / V-(3-(2-(1 methyl-1 H-pyrazol-3-yl)benzyl)- 4oxo-3,4-d¡hydroquinazolin-5yl)benzamide 106 0 II nh2 ck Yk 1 | Y NH O o=s=o today óóA 3,5-dichloro-4-hydroxy- / V-(4-oxo3-(2-sulfamoylbenzyl)-3,4dihydroquinazolin-5yl)benzamide 107 m / Cl XY, \ .OH CuLQ a ζΧγ'Ν or A / -(5-benzyl-1 -methyl-4-oxo-4,5dihydro-1 H-pyrazolo[3,4d]pyrimidin-3-yl)-4,6-dichloro- 5hydroxypicolinamide oonRhn / cznz / a / υιλι Ex. Structure Name 108 o TFA salt of 4,6-dichloro-5hydroxy-A / -(4-oxo-3-((1 R,2S)-2phenylcycloprop¡l)-3,4dihydroquinazolin-5yl)picolinamide 109 0 CK^N A -V A or 4,6-dichloro-5-hydroxy-A / -(4-oxo3-((1 S,2F?)-2-phenylcyclopropyl)3,4-dihydroquinazolin-5yl)picolinamide 110 ? o hoa k) Au 4,6-dichloro-5-hydroxy-A / -(4-oxo3-(2-(pyridin-2-yl)benzyl)-3,4dihydroquinazolin-5¡l)picolinamide 111 ? o ciWnh o V h°a ó0a5 3,5-dichloro-4-hydroxy-A / -(4-oxo3-(2-(pyridin-2-yl)benzyl)-3,4dihydroquinazolin-5-yl)benzamide 112 O 9 Ω YA A or 3,5-dichloro-4-hydroxy-A / -(8-methyl4-oxo-3-(2- (trifluoromethoxy)benzyl)-2(trifluoromethyl)-3,4dihydroquinazolin-5-yl)benzamide 113 O F ckxN^ A AH Yf NH 0 O F ho lucVó Cl A / UAY) AY I 4,6-dichloro-5-hydroxy-N-(1-methyl2,4-dioxo-3-(2- (trifluoromethoxy) benzyl)-1,2,3,4tetrahydroquinazoline-5- ¡l)picol¡namide 114 HO k Al CI-^ / YZ °*k A c / S<'n' / ^aAi Λ I H | NA f-AA 5-(4,6-dichloro-5hydroxy¡p¡cholínamido)-N-(2fluorobenzyl)-3-methylisothiazole-4carboxamide 115 HO k Al αΎΪ Νγ 0¼ U I cók (S)-5-(4 ,6-dichloro-5hydroxy¡p¡colinamido)-N-(1 -(2fluorophenyl)ethyl)-3-methyl¡sothiazol4-carboxamide 116 H0A Ονίζθ α^γΝΗ o o 3,5-dichloro-4-hydroxy¡-N- (4-oxo3-(2-phenylcyclopropyl)-2(trifluoromethyl)-3,4dihydroquinazolin-5yl)benzamide Ex. Structure Name 117 0 Ck A. Y NH 0 h°t Cl YA NY 3,5-dichloro-4-h idroxy-N-(3-((1 methyl-1 H-índazol-3-íl) methyl)-4oxo-3,4-dihydroquanazoln-5yl)benzamide 118 0 u HnA^ OT O?N M ~ c / °H f^Tf F 3,5-dichloro-4-hydroxy¡-N -(1-methyl4-oxo-5-(2- (trifluoromethoxy)benzyl)-4,5dihydro-1 H-pyrazolo[3,4djpyrimidin- 3-!l)benzamide 119 0 ΥΆ CCto M ^hT N OH I \ Cl fTf F 4,6-dichloro-5-hydroxy-N-(1 -methyl4-oxo-5-(2- (trifluoromethoxy)benzyl)-4,5dihydro-1 H-pyrazolo[3, 4d]pyrimidine- 3-¡l) picolinamide 120 OH ci\Av / ci Π H ípl \YvNYv O G^F τ F 1-(4,6-dichloro-5h¡droxyp¡choline¡l)-N-(2( trifluoromethoxy)benzyl)p¡perid¡n a-2-carboxamide 121 O___.- - YY fyv ° \__ / I Z / ^° tAx HjQ 3,5-dichloro-4-hydroxy-N-( 4-oxo3-((1S,2R)-2-phenylcyclobut¡l)-3,4dihydroquinazolin-5yl)benzamide 122 0 Ck z+s. A Yy nh o H0L ÓÓXJ N cr N 3,5-dichloro-N-(3-((2chloropyridin-3-¡l)methyl)-4-oxo3,4-dihydroquinazolin-5-¡l )-4hydroxybenzamide 123 0 ^0 0 rN^ H0Y ÓO u 3,5-dichloro-4-hydroxy¡-N-(3-(2morpholino-1 -phenylethyl)-4-oxo-3,4dihydroquinazolin-5yl)benzamide 124 U NH O O F ΗΟ' / <ϊγ νΥΑνΥΥ ¿ uV u 3,5-dichloro-4-hydroxy¡-N-(4-oxo3-(2-(trifluoromethoxy)benzyl)3,4-dihydropy¡do[4 ,3d]pyri¡mid¡n-5-¡l)benzam¡da Ex. Structure Name 125 Cl HO-^k~V Cl „ nh 0 Fbv° 5-(3,5-dichloro-4hydroxybenzamide)-N-(2(trifluoromethoxy)benzyl)-2(trifluoromethyl)thiazol- 4carboxamide 126 HO k χθΙ ο^τ i i Cl- / Y F νψ Ci ° °YC 0 1-(4,6-dichloro-5hydroxypicolino¡l)-N-(2(trifluoromethoxy)benzyl)pyrrolidine -2-carboxamide 128 lki5 ZI or -Π or 1-( 3,5-dichloro-4-hydroxy¡benzoyl)N-(2- (trifluoromelox¡)benzyl)pyrrolidin -2-carboxamide 129 .o¿X«l:O C|A^NH 0 0 4 ,6-dichloro-N-{3-[(2-chloropyridin3-¡l)methyl]-4-oxo-3,4dihydroquinazolin-5-yl}-5hydroxypyridin-2-carboxamide 130 -¿W> C|A ^NH 0 0 3,5-dichloro-N-{3-[(3fluoropyridin-2-yl)methyl]-4-oxo3,4-dihydroquinazolin-5-yl}-4hydroxybenzamide Ex. Structure Name 131 OH ci^Axi I il 0 ΗΝίΆ) oróíV F^F F 4,6-dichloro-5-hydroxy¡-N-(6-met¡l4-oxo-3-{[2- (trifluoromethoxy)phen ¡l]methyl}-3,4dih¡droqu¡nazolin-5-¡l)pyrídin-2carboxamide 132 0 A XI 0 HN Y Y y<OH i^. As. y & o n AF f 3,5-dichloro-N-(8-fluoro-4-oxo-3{[2-(trifluoromethoxy)phenyl]methyl}3,4-dihydroquinazolin-5-yl) -4hydroxybenzamide 133 0 o hnX^Y01 ιΧτ^Ν>τιΐ T0H As.A ci o n F^F F F 4,6-dichloro-N-(8-fluoro-4-oxo-3{[2-(trifluoromethoxy)pheníl ]met¡l}3,4-dihydroquinazolin-5-yl)-5hydroxypyridine-2-carboxamide 134 Cl ho^A^n l Ay° Cl / NH C\ h \ b 0 Fw° fA F 4,6-dichloro-5 -hydroxy¡-N-[2-({[2(trifluoromeloxy)phen¡l]met¡l}carb amoyl)cyclopentyl]pyrid¡n-2carboxamide 137 -¿WO C|A^NH 0 0 3 ,5-dichloro-N-{3-[(2fluoropyridin-3-yl)methyl]-4-oxo3,4-dihydroquinazolin-5-yl}-4hydroxybenzamide 138 F\^N. hoAnWnA5 A\A\ / NH 0 cr y 0 4,6-dichloro-N-{3-[(2fluoropyridin-3-yl)methyl]-4-oxo3,4-dihydroquinazolina-5-¡l} -5hydroxypyridine-2-carboxamide Ex. Structure Name 140 o_ Ω vd / =\ χο λα z / =° 4,6-dichloro-A / -(3-((3-fluoropyridin-2-¡l)met¡l)-4-oxo3,4 -dihydroquinazolin-5-yl)-5hydroxypicolinamide 141 OH Ck Λ ,α Η T xX F'óC Ο^ΝΗ O / O d¿i 4,6-dichloro-A / -(2,8-dimethyl-4oxo-3- (2- (trifluoromelox¡)benzyl)-3,4dihydroquinazo¡n-5-¡l)-5hydroxypicolinamide 142 OH CI^ / L / CI O^NH 0 CF3 3,5-dichloro-N-(2 ,8-dimet¡l-4oxo-3-((2-(trifluoromethyl)pyridin3-¡l)methyl)-3,4-dihydroquinazolin-5-yl)-4hydroxybenzamide 143 OH c^ / L / O! TjT O^NH 0 Cl ÓVrj 3,5-dichloro- / V-(3-((3- chlorop¡ridín-2-¡l)met¡l)-4-oxo3,4-dih¡droquinazolin-5 -yl)-4hydroxybenzamide 144 OH Cl_l Cl F Y J.F 1 F^O 0 HN^O 4,6-dichloro-5-hydroxy¡- / V((1S,2S)-2-((2- (trifluoromethox¡)benc ¡l)carbam ¡l)cyclohexyl)p¡cholinamide 145 OH CI-xJ^ / CI V KF 1 F^O 0 Hhdo rfV^Ndrd Η Ί η II 4,6-dichloro-5-hydroxy¡- / V - ((1 R,2R)-2-((2- (trifluoromethoxy)benzyl)carbamoyl)cyclohexyl)p¡cholinamide oonRhn / cznz / a / υιλι Ex. Structure Name 146 0 CK A II Ap NH 0 CF3 hlQ'^k [|A^NXAÍ1 ci A 3,5-dichloro-A / -(2,8-dimet¡l-4oxo-3-((3- (trifluoromethyl)pyridin- 2-¡l)methyl)-3,4- dihydroquinazolin-5-¡l)-4- hydroxybenzamide 147 OH □^Α,α ΧγΝ Ο^ΉΗ 0 CF3 Aky-' xA γΑΝΑ^ AA 4,6-dichloro-A / -(2,8-dimethyl-4oxo-3-((2-(trifluoromethyl)pyridin-3-yl)methyl)- 3,4- dihydroquinazolin-5-¡l)-5- hydroxypicolinamide 148 OH c|\A>wci II 1 nA O^NH 0 Cl k-A k NXJ 4,6-dichloro-A / -(3-(( 3-chloropyridin-2-yl)methyl)-4-oxo3,4-dihydroquinazolin-5-yl)-5hydroxypicolinamide 149 OH °|\Αγ'01 O^NH 0 OCF3 ¿oru N CF2H<^ 3,5- dichloro-A / -(2-(difluoromethyl)8-methyl-4-oxo-3-(2(trifluoromethoxy¡)benzyl)-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 150 OH CI^ A / CI H | A AF O^NH O oA úortb F 4,6-dichloro-N-(8-fluoro-2-methyl4-oxo-3-(2- (trifluoromethoxy¡)benzyl)-3,4dihydroquinazolin-5-yl) -5hydroxypicolinamide 151 O CK / ^A fAf γγ NH 0 y hoA ψίτύ 3,5-dichloro-N-(2,8-dimethyl-4oxo-3-(2-(trifluoromethyl)benzyl)3,4-d¡ hydroquinazolin-5-1)-4hydroxybenzamide oonRhn / cznz / a / υιλι Ex. Structure Name 152 OH CI\Jx.CI Cr NH 0 Ο^Έ Ócboó A 1 F 3,5-dichloro-N-(2-(fluoromethyl)-8methyl-4-oxo-3-(2 - (trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5-¡l)-4hydroxybenzamide 153 O Clx A Ay NH o cf3 γ / οϊ 4,6-dichloro-A / -(2,8-dimethyl-4oxo -3-((3-(trifluoromethyl)p¡r¡d¡n2-¡l)methyl)-3,4- dihydroquinazolin-5-yl)-5hydroxypicolinamide 154 u Ck / x, A FX|ZF Y j nh o y H C>y l|j N ^^Tll Cl ykA A F 3,5-dichloro-N-(8-fluoro-2-methyl4-oxo-3-((3- (trifluoromethyl)pyr¡d¡n- 2-¡l)methyl¡l)3,4-dihydroquinazolin-5-yl)-4hydroxybenzamide 155 u ciiTnh ° F'^fF Hcry <αα<ν γη Cl ί / Ά A F 4,6-dichloro-A / -( 8-fluoro-2-methyl4-oxo-3-((3- (trifluoromethyl)pyridín-2-íl)methyl)3,4-díhydroquinazolin-5-íl)-5hydroxypicolinamide 156 u Cl Π NH 0 T η οηχ> ífjT N ^Yh ci A N Cl 3,5-dichloro-N-(8-chloro-2-methyl4-oxo-3-(2- (trifluoromethyl)benzyl)-3,4dih¡ droquinazolin-5-¡l)-4hydroxybenzamide 157 OH ClxJx^CI O^NH 0 I ocf3 A Y N \ F 3,5-dichloro-N-(8-fluoro-2-methyl4-oxo-3-(1-(2- (trifluoromethoxy)phenyl)ethyl)-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide oonRhn / cznz / a / υιλι Ex. Structure Name 158 OH α^Υ^οι O^NH 0 CF3 F 3,5-dichloro-N-(8-fluoro-2-methyl4-oxo-3-(2- (trifluoromethyl)benzyl)-3,4dih ¡droquinazolin-5-¡l)-4hydroxybenzamide 159 OH Cl^ / k^CI ΊγΝ O^NH 0 CF3 0Λγύ5 F 4,6-dichloro-N-(8-fluoro-2-methyl4-oxo-3-(2- (trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide 160 OH Cix / Lx1 Yj O^NH O OCF3 óóró Y N CFjÍF^ 4,6-dichloro-N-(2-(difluoromethyl)8-methyl -4-oxo-3-(2- (trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide 161 0 CK Jk | Y NH O r^\ “Ύ kk'i'boci y / - y 3,5-dichloro-N-(2,8-dimethyl-3-((1 methyl-1 H-indazol-3-yl) met¡l)-4oxo-3,4-dihydroquinazolin-5-¡l)4 -hydroxybenzamide 162 CX / z \ 1 °y5 o ? 4,6-dichloro-N-(2,8-dimethyl-3-((1 methyl-1 H-indazol-3-yl)methyl)-4oxo-3,4-dihydroquinazolin-5-yl)- 5 -hydroxypicolinamide 163 0 CA / N. Jk fJ\f Yj Y NH 0 H0^i ci γΆ V 4,6-dichloro-A / -(2,8-dimethyl-4oxo-3-(2-(trifluoromethyl)benzyl)3,4- dihydroquinazolina-5-íl)-5hydroxypicolinamide oonRhn / cznz / a / υιλι Ex. Structure Name 164 0 CK A NH 0 cf3H°X|X> ιίΊΓ^ΝΑιΊ ci AA.A [ N CF2H 3,5-dichloro-A / -(2-(difluoromethyl)8-methyl-4-oxo-3 -((3- (trifluoromethyl)pyrídin-2-¡l)methyl)3,4-dihydroquinazolin-5-yl)-4hydroxybenzamide 165 OH Y Y O*W 0 CF3 μΛι^ιΛ CI 4,6- dichloro-A / -(8-chloro-2-methyl4-oxo-3-((3- (trifluoromethyl)pyridín-2-¡l)methyl)3,4-dihydroquinazolin-5-yl) -5hydroxypicolinamide 166 OH ClxA^Oi O^MH O CF3 YJk <Y hk Y CI 3,5-dichloro-A / -(8-chloro-2-methyl4-oxo-3-((3- (trifluoromethyl)p ¡r¡d¡n-2-¡l)met¡l)3,4-dihydroquinazolin-5-yl)-4- hydroxybenzamide 167 OH Clx^A.01 Ο^ΉΗ 0 yOF3 A 3,5-dichloro -A / -(2-(difluoromethyl)8-methyl-4-oxo-3-(2- (trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 168 n u [X fvf l'>j^5>p'NH o f ηοΆ^ AfV ci AA -A y N F 3,5-dichloro- / V-(8-fluoro-2-methyl4-oxo-3-(2- ( trifluoromeloxy)benzyl)-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 169 OH d^A^ A Oí fvf O^NH 0 γ^Ό A L A A D ¡A dd 3,5-dichloro-4-hydroxy¡- N-(8-methyl2-(methyl-d3)-4-oxo-3-(2(tnfluoromethoxy¡)benzyl)-3,4dihydroquinazolin-5-yl)benzamide oonRbn / cznz / a / υιλι Ex. Structure Name 170 o Cl\ Y A fJi ,f y NH 0 Y H lli N Ά^ΙΙ ci L <a a aa oi 4,6-dicloro-n-(8-cloro-2-metil4-oxo-3-(2- (trifluorometil)bencil)-3,4dih¡droquinazolin-5-¡l)-5hidroxipicolinamida 171 o— =\>°c> °A, φΡ 3,5-dichloro-N-(8-fluoro-2-(methyld3)-4-oxo-3-(2-(trifluoromethyl)benzyl)-3,4d¡hydroquinazolin-5-yl )-4hydroxybenzamide 172 0 ckA ll NH 0 Cl ncry A[ NAA Cl LAnA nY 3,5-dichloro- / V-(3-((3-chloropyridin-2-yl)methyl)-2,8dimethyl-4-oxo- 3,4dihydroquinazolin-5-¡l)-4hydroxybenzamide 173 OH d^A / cl O^NH 0 I ocf3 <Αό F (S)-3,5-dichloro-A / -(8-fluoro-2methyl-4 -oxo-3-(1-(2- (trifluoromethoxy)phen¡l)ethyl)-3,4dihydroquinazolin-5-¡l)-4hydroxybenzamide 174 Ϊ A ck A Y| and NH 0 -_ O F ho^ / ΓιΤ νΑιί Cl AA Ά F (R)-3,5-dichloro-A / -(8-fluoro-2methyl-4-oxo-3-(1-(2- (trifluoromethoxy) phen¡l)ethyl)-3,4dihydroquinazolin-5-¡l)-4hydroxybenzamide 175 0 CK _N. A A^ Aj'A, Cl or rac-4,6-dichloro-5-hydroxy-N-(4oxo-3-((1 R,2S)-2phenílcyclobutyl)-3,4dihydroquinazolin-5íl) picol¡nam¡da 176 OH α^Αγ! II 1 -3-(2(tnfluoromethox¡)benzyl)-3,4dihydroquinazolin-5¡l)picol¡nam¡da QQnptrn / cznz / a / υιλι Ex. Structure Name 177 Ύ A o cf3 ho^Y ΙιΊ ci AA..A nA | N cf2h 4,6-dichloro-A / -(2-(difluoromethyl)8-methyl-4-oxo-3-((3- (trifluoromethyl)pyrídin-2-¡l)methyl)3,4 -dihydroquinazolin-5-yl)-5hydroxypicolinamide 178 o V / nh 0 Cl HOV AYA Cl nJ 4,6-dichloro-N-(3-((3-chloroprídin-2-yl)methyl)- 2,8dimethyl-4-oxo-3,4- dihydroquinazolin-5-¡l)-5hydroxypicolinamide 179 OH CIAúzCI y X CA 0^ NH O XX 3,5-dichloro-4-hydroxy¡-N-(8- methyl2-(methyl-d3)-4-oxo-3-(2(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-yl) benzamide 180 OH CI-^Aj / CI IAn X ULf O NH 0 Y K ©A D 4,6-dichloro-5-hydroxy¡-N-(8-methyl2-(methyl-d3)-4-oxo-3-(2(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-yl) picolinamide 181 o_p sA JA 4,6-dichloro-N-(2-(difluoromethyl)8-methyl-4-oxo-3-(2- (trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-¡l)- 5-hydroxypicolinamide 182 HO \ .Cl C'AJ ΥΊ YA 5-(3,5-dichloro-4hydroxybenzamide)-N-(2(trifluoromethyl)benzyl)thiazole-4carboxamide 183 O CK / s A X ^A NH O F Η0^τ íT^i νΑί Cl Y%nA 3,5-dichloro-N-(3-((3fluoropyrádin-2-yl)methyl)-2,8dimethyl-4-oxo-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide Ex. Structure Name 184 LL LL O= or ? 4,6-dichloro-N-(8-fluoro-2-(methyld3)-4-oxo-3-(2-(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-íl)-5hydroxypicolinamide 185 HO\ ,CI Cl ΙΪ ,· jC n ° v xTX η \^N H 5-(3,5-dichloro-4hydroxy¡benzamido)-N-(2(trifluoromethyl)benzyl)thiazole-4carboxamide 186 OH c|\xAci ior T F O^NH 0 FAF 3,5-dichloro-N-(2-(fluoromethyl)-8methyl-4-oxo-3-(2- (trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 187 OH Ci-X / Lx! H J 0 A ° S\AA^'n%A \ h VA# NV \ 5-(4,6-dichloro-5hydroxy¡p¡cholinam¡do)-N-((1 methyl-1 H-indazol-3- ¡l)methyl)thiazol-4-carboxamide 188 A ZI O^ / °\ ΠΞ -dichloro-4hydroxybenzamide)-N-((1 -methyl1 H-indazol-3-yl)methyl)thiazole-4carboxamide 189 HO \ OI CIVXÍ Xa? 5-(4,6-dichloro-5hydroxy¡p¡cholinamide)-N-(3fluorobenzyl)thiazole-4carboxamide oonRhn / cznz / a / υιλι Ex. Structure Name 190 OH CixJx / GI or O^NH 0 ArP F 3,5-dichloro-N-(8-fluoro-2-methyl3-((1 -methyl-1 H-indazol-3yl)methyl)-4 -oxo-3,4dihydroqu¡nazolin-5-¡l)-4hydroxybenzamide 191 HO \ Cl and Vf oAnH o 0 F sC^hCII \=N H 5-(4,6-dichloro-5hydroxyp¡col¡nam¡do)- N-(2(trifluoromethoxy¡)benzyl)thiazole-4carboxamide 192 - oH1 IZ \^o ¡ z O or ΞΕ 5-(4,6-dichloro-5hydroxy¡picol¡nam¡do)-N-( 2(trifluoromethyl)benzyl)thiazol-4carboxamide 193 Cl 1 OH Q / NH <\C h Π S PF 5-(4,6-dichloro-5hydroxy¡p¡cholinam¡do)-N-((6(trifluoromethyl )pyrídin-2¡l)methyl)thiazol-4-carboxamide 194 OH CI^Á ,d O^NH O ΔΑχΒΡ n~n N N\ F 4,6-dichloro-N-(8-fluoro -2-methyl3-((1 -methyl-1 H-indazol-3yl)methyl)-4-oxo-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide 195 s__ / =\ / ° h z, )=o B- 4 ,6-dichloro-N-(3-((3-fluoropyridín-2-¡l)methyl)-2,8dimethyl-4-oxo-3,4-dihydroquinazolin-5-yl)-5hydroxypicolinamide oonRhn / cznz / a / υιλι Ex. Structure Name 196 I o O x yVQ ví A O=\ I o zm -n 5-(4,6-dichloro-5hydroxy¡p¡cholinamate)-N-((3(trifluoromethyl)pyridín -2¡l)methyl)thiazol-4-carboxamide 197 0 exA NH O F A A A A AF ho t| y n Y Y f Cl LA- A J F 3,5-dichloro-N-(8-fluoro-2-methyl4-oxo-3-((6- (trifluoromethyl)pyr¡d¡n-2-¡l)met¡ l)3,4-dihydroquinazolin-5-yl)- 4-hydroxybenzamide 198 O οιγΛΗ ? Ay s'j^bj'AíA HO \ V=N o Y F f F 5-(3,5-dichloro-4hydroxybenzam¡do)-N-((6(trifluoromet¡l)pyr¡d¡n-2 ¡l)methyl)thiazol-4-carboxam¡da 199 0 Ckz^A / | NH 0 / A A A ,CFo hoA γτσ 3,5-dichloro-A / -(2,8-dimethyl-4oxo-3-((6-(trifluoromethyl)pyr¡din- 2-¡l) methyl)-3,4-dihydroquinazolin-5-yl)-4-hydroxybenzamide 200 or Cl\ / ¾. A YY^ NH 0 D D CF3H0 ίίΊΛ'Ν'ΧΓΪΙ ci AA A AJ Y N 3,5-dichloro-N-(2,8-dimet¡l-4oxo-3-((2- (trifluoromet¡l)phen¡l )methyl-d2)3,4-dihydroquinazolin-5-yl)-4hydroxybenzamide 201 0 Cl\ / N. A Y Y NH 0 D D CF3H0 ííi^N^rii ci LxA A A A Y^ N 4,6-dichloro-N-(2,8-dimethyl-4oxo-3-{[2- (trifluoromethyl)phen¡l](2H2)met¡ l}3,4-dihydroquinazolin-5-yl)-5hydroxypyridine-2-carboxamide 202 OH ClxJ^.CI O^NH 0 r~^ γ O 4,6-dichloro-N-(2,8-dimethyl- 4oxo-3-((1 R,2S)-2phenylcyclobutyl)-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide oonRhn / cznz / a / υιλι Ex. Structure Name 203 OH αΑγα (AnH O A 3,5-dichloro-N-(2,8-dimethyl-4oxo-3-((1 R,2S)-2phenylcyclobutyl)-3,4dihydroquinazolin-5-yl)-4hydroxybenzamide 204 0 ci\A AA NH ° cf3 xi N Ail ci L LA )-4hydroxybenzamide 205 o_ o—C: / =\ A° z A° B o ω 4,6-dichloro-N-(2,8-dimethyl-4oxo-3-((6-(trifluoromethyl)p¡ rid¡n2-¡l)methyl)-3,4- dihydroquinazolin-5-yl)-5hydroxypicolinamide 206 0 4-oxo-3(2-(trifluoromethyl)benzyl)-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide 207 O CXNANH o ΗΟ^γ AXnA Cl Aa Ó 4,6-dichloro-A / -(8-fluoro-2 -methyl4-oxo-3-((1S,2R)-2phenylcyclobutyl)-3,4dihydroquinazolin-5-yl)-5hydroxypicolinamide Additional Forms of Compounds Disclosed Herein Isomers / Stereoisomers In some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein possess one or more double bonds. The compounds presented herein include all cis, trans, syn, anti, entgegen (E) and zusammen (Z) isomers, as well as corresponding mixtures thereof. In some situations, the compounds described herein possess one or more chiral centers and each center exists in the R configuration or S configuration. The compounds described herein include all diastereomeric, enantiomeric and epimeric forms, as well as their corresponding mixtures. In additional embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereoisomers, resulting from a single preparatory step, combination or interconversion, are useful for the applications described herein. In some embodiments, the compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereomeric compounds, separating the diastereomers and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are preferred. In some embodiments, diastereoisomers have different physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and are separated by taking advantage of these differences. In some embodiments, the diastereoisomers are separated by chiral chromatography or, preferably, by separation / resolution techniques based on solubility differences. In some embodiments, the optically pure enantiomer is then recovered, along with the resolving agent, by any practical means that does not result in racemization. Labeled compounds In some embodiments, the compounds described herein exist in their isotopically labeled forms. In some embodiments, the methods described herein include methods of treating diseases by administering such isotope-labeled compounds. In some embodiments, the methods described herein include methods of treating diseases by administering said isotopically labeled compounds as pharmaceutical compositions. Therefore, in some embodiments, the compounds described herein include isotopically labeled compounds, which are identical to those listed herein, but in that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number normally found in nature. Examples of isotopes that may be incorporated into the compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chloride, such as 2H,3H,13C,14C,15N,18O,17O,31P ,32P,35S,18F, and36CI, respectively. The compounds described herein and pharmaceutically acceptable salts, solvates or stereoisomers thereof containing the aforementioned isotopes and / or other isotopes of other atoms are within the scope of this invention. Certain isotopically labeled compounds, for example those in which radioactive isotopes such as 3H and 14C are incorporated, are useful in tissue distribution assays of drugs and / or substrates. Tritiated, i.e. 3H and carbon-14, i.e. 14C isotopes are particularly preferred for their ease of preparation and detectability. Furthermore, substitution with heavy isotopes such as deuterium, i.e. 2H, produces certain oonRhn / cznz / a / υιλι therapeutic advantages resulting from increased metabolic stability, for example, increased in vivo half-life or reduced dosage requirements. In some embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent tags, or chemiluminescent tags. In some embodiments, the labeled compounds described herein are used to measure in vitro and in vivo binding of unlabeled HSD17B13 inhibitors. Pharmaceutically acceptable salts In some embodiments, the compounds described herein exist as their pharmaceutically acceptable salts. In some embodiments, the methods described herein include methods of treating diseases by administering such pharmaceutically acceptable salts. In some embodiments, the methods described herein include methods of treating diseases by administering such pharmaceutically acceptable salts as pharmaceutical compositions. In some embodiments, the compounds described herein possess acidic or basic groups and therefore react with any of various inorganic or organic bases and inorganic and organic acids to form a pharmaceutically acceptable salt. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds disclosed herein, or a solvate or stereoisomer thereof, or by separately reacting a purified compound in its free form with a suitable acid or base, and isolating the salt thus formed. Examples of pharmaceutically acceptable salts include salts prepared by reaction of the compounds described herein with a mineral, an organic acid or an inorganic base, such salts include acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate , bisulfite, bromide, butyrate, butyn-1,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanepropionate, decanoate, digluconate, dihydrogen phosphate, dinitrobenzoate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate , glycolate, hemisulfate, heptanoate, hexanoate, hexino-1,6-dioate, hydroxybenzoate, y-hydroxybutyrate, hydrochloride, hydrobromide, iodide, 2-hydroxyethanesulfonate, iodide, isobutyrate, lactate, maleate, malonate, methanesulfonate, mandelate metaphosphate, methanesulfonate, methox i benzoate, methylbenzoate, monohydrogen phosphate, 1-naphthalenesulfonate, 2naphthalenesulfonate, nicotinate, nitrate, palmoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenylacetate, phenylbutyrate, , salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylate, unconate and xylenesulfonate. oonRhn / cznz / a / υιλι Additionally, the compounds described herein can be prepared as pharmaceutically acceptable salts formed by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid, including, but not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, acid sulfuric acid, nitric acid, phosphoric acid, metaphosphoric acid and the like; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, melic acid, maleic acid, fumaric acid, p-toluenesulfonic acid, tartaric acid, trifluoroacetic acid acid, citric acid, benzoic acid, 3-(4-hydroxybenzo¡l)benzo¡ic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1carboxylic acid) , 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid and muconic acid. In some embodiments, other acids, such as oxalic acid, although not themselves pharmaceutically acceptable, are used in the preparation of salts useful as intermediates to obtain the compounds described herein, solvate or stereoisomer thereof and its salts. pharmaceutically acceptable acid addition. In some embodiments, the compounds described herein comprising a free acid group react with a suitable base, such as the hydroxide, carbonate, bicarbonate, sulfate, of a pharmaceutically acceptable metal cation, with ammonia or with a primary, secondary organic amine pharmaceutically acceptable tertiary or quaternary. Representative salts include alkali or alkaline earth salts, such as lithium, sodium, potassium, calcium and magnesium, and aluminum salts and the like. Illustrative examples of bases include sodium hydroxide, potassium hydroxide, choline hydroxide, sodium carbonate, N+(61-4 alkyl)4, and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. It should be understood that the compounds described herein also include quaternization of any nitrogen-containing basic groups they contain. In some embodiments, products soluble or dispersed in water or oil are obtained by said quaternization. Solvates oonRhn / cznz / a / υιλι In some embodiments, the compounds described herein exist as solvates. The invention provides methods for treating diseases by administering said solvates. The invention further provides methods for treating diseases by administering such solvates as pharmaceutical compositions. Solvates contain stoichiometric or non-stoichiometric amounts of a solvent and, in some embodiments, are formed during the crystallization process with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates when the solvent is alcohol. Solvates of the compounds described herein may conveniently be prepared or formed during the processes described herein. By way of example only, hydrates of the compounds described herein can conveniently be prepared by recrystallization from an aqueous / organic solvent mixture, using organic solvents including, but not limited to, dioxane, tetrahydrofuran or methanol. Furthermore, the compounds provided herein may exist in solvated and unsolvated forms. In general, solvated forms are considered equivalent to unsolvated forms for the purposes of the compounds and methods provided herein. Tautomers In some situations, compounds exist as tautomers. The compounds described herein include all possible tautomers within the formulas described herein. Tautomers are compounds that are interconvertible by migration of a hydrogen atom, accompanied by a change of a single bond and an adjacent double bond. In bonding arrangements where tautomerization is possible, there will be a chemical equilibrium of the tautomers. All tautochemical forms of the compounds described herein are contemplated. The exact ratio of tautomers depends on several factors, including temperature, solvent, and pH. Treatment method Provided herein are methods of inhibiting the expression or activity of HSD17B13, which may be useful for treating, preventing or ameliorating a disease associated with HSD17B13 in a subject in need, such as NAFLD or NASH, by administering a compound. that targets HSD17B13, or one of its pharmaceutically acceptable salts, solvates or stereoisomers. Provided herein are methods of inhibiting the expression or activity of HSD17B13 in a cell comprising contacting the cell with a described HSD17B13 inhibitor or one of its pharmaceutically acceptable salts, solvates or stereoisomers, thereby inhibiting the expression or activity of HSD17B13 in the cell. In some embodiments, the cell is a hepatocyte cell. In some embodiments, the cell is in the liver. In some embodiments, the cell is in the liver of a subject who has, or is at risk for having, a disease, disorder, condition, symptom or physiological marker associated with a liver disease, metabolic disease or cardiovascular disease or disorder. In some embodiments, the cells are adipocytes or monocytes from a subject who has or is at risk for having a disease. In some embodiments, the cells are lymphocytes of a subject who has or is at risk of having a disease. In some embodiments, the liver disease, metabolic disease or cardiovascular disease or disorder is metabolic syndrome, fatty liver disease, chronic liver disease, liver cirrhosis, hepatic steatosis, steatohepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease , nonalcoholic steatohepatitis (NASH), fulminant Wilson's disease, rapidly fibrosing hepatitis C viral lesion, and decompensated portal vein hypertension. In some embodiments, the liver disease, metabolic disease, or cardiovascular disease or disorder is NASH. In some embodiments, the liver disease, metabolic disease, or cardiovascular disease or disorder is a cholestatic liver disease. In some embodiments, the liver disease is primary biliary cirrhosis or primary sclerosing cholangitis. Provided herein are methods of treating, preventing, delaying the onset, slowing the progression of, or ameliorating one or more diseases, disorders, conditions, symptoms, or physiological markers associated with HSD17B13 comprising administering to a subject in need thereof a compound described in herein, or one of its pharmaceutically acceptable salts, solvates or stereoisomers. In some embodiments, the subject in need is identified as having, or at risk of having, the disease, disorder, condition, symptom or physiological marker. In some embodiments, the liver disease, metabolic disease or cardiovascular disease or disorder is metabolic syndrome, liver disease, fatty liver disease, chronic liver disease, liver cirrhosis, hepatic steatosis, steatohepatitis, alcoholic liver disease, non-alcoholic fatty liver disease. (NAFLD) and non-alcoholic steatohepatitis (NASH). In some embodiments, the liver disease, metabolic disease, or cardiovascular disease or disorder is NASH. This document provides methods to reduce, improve or regulate hepatic steatosis, liver fibrosis, triglyceride synthesis, lipid levels, liver lipids, ALT levels, NAFLD activity score (ÑAS). cholesterol levels or triglyceride levels, or a combination thereof, in a subject in need thereof comprising administering to the subject a compound described herein, or one of its salts, solvates or stereoisomers pharmaceutically acceptable. In some embodiments, the compound described herein oonRhn / cznz / a / υιλι document, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, ameliorating or regulating hepatic steatosis in the individual. . In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, ameliorating or regulating liver fibrosis in the individual. In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, improving or regulating triglyceride synthesis in the individual. In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, improving or regulating lipid levels in the individual. In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, improving or regulating hepatic lipids in the individual. In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, improving or regulating ALT levels in the individual. In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, improving or regulating the NAFLD activity score in the individual. In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, improving or regulating cholesterol levels in the individual. In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, is provided for use in reducing, improving or regulating triglyceride levels in the individual. In some embodiments, the subject is identified as having, or being at risk for having, a disease, disorder, condition, symptom, or physiological marker associated with a liver disease, a metabolic disease, or a cardiovascular disease or disorder. In some embodiments, the liver disease, metabolic disease or cardiovascular disease or disorder is metabolic syndrome, liver disease, fatty liver disease, chronic liver disease, liver cirrhosis, hepatic steatosis, steatohepatitis, nonalcoholic fatty liver disease (NAFLD) and steatohepatitis. non-alcoholic. (NASH). In some embodiments, the liver disease, metabolic disease, or cardiovascular disease or disorder is NASH. Methods are provided herein to treat, prevent, or delay the onset of drug-induced liver injury (DILI) in a subject in need. In some oonRhn / cznz / a / υιλι modalities, the liver injury is steatohepatitis. Also provided herein are methods to treat, prevent, or delay the onset of drug-induced steatohepatitis (DISH) in a subject in need. In some embodiments, the subject in need is receiving chemotherapy to treat the cancer. In some embodiments, the subject in need is receiving treatment for a cardiovascular disease. In some embodiments, the subject in need is receiving treatment for a psychiatric illness / condition. In some embodiments, the subject in need is receiving pain treatment. In some embodiments, the subject in need is receiving treatment for arthritis. In some embodiments, the chemotherapy is tamoxifen, toremifene, irinotecan, methotrexate, fluorouracil (5-FU), or any combination thereof. In some embodiments, the subject in need receives amiodarone, perhexiline, propranolol, or any combination thereof. In some embodiments, the subject in need receives amitriptyline, clozapine, or any combination thereof. In some embodiments, the subject in need receives methotrexate, pirprofen, or any combination thereof. Dosage In certain embodiments, compositions containing the compounds described herein are administered for prophylactic and / or therapeutic treatments. In certain therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially stop at least one of the symptoms of the disease or condition. Effective amounts for this use depend on the severity and course of the disease or condition, prior therapy, the patient's health status, weight and response to medications, and the judgment of the treating physician. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose-escalation and / or dose-ranging clinical trial. In prophylactic applications, compositions containing the compounds described herein are administered to a patient susceptible to or at risk for a particular disease, disorder or condition. Said amount is defined as a prophylactically effective amount or dose. In this use, the precise amounts also depend on the patient's health, weight and the like. When used in patients, effective amounts for this use will depend on the severity and course of the disease, disorder or condition, prior therapy, the patient's health status and response to medications, and the judgment of the treating physician. . In one aspect, prophylactic treatments include administering to a mammal, which previously experienced at least one symptom or risk factor of the disease being treated and is currently in remission, a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt thereof, to prevent a return of symptoms of the disease or condition. In one aspect, prophylactic treatments include administering to a mammal having patatin-like phospholipase domain-containing polymorphism 3 (PNPLA3), a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt thereof. , to prevent liver damage. The protein variant 148 Isoleucine to Methionine (I148M) of patatin-like phospholipase domain containing 3 (PNPLA3), a protein that is expressed in the liver and is involved in lipid metabolism, has recently been identified as an important determinant of fat content in the liver. Several studies confirmed that the I148M variant predisposes to the full spectrum of liver damage associated with fatty liver: from simple steatosis to steatohepatitis and progressive fibrosis. Furthermore, the I148M variant represents an important determinant of the progression of alcohol-related steatohepatitis to cirrhosis, and of influencing fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis, and possibly in the chronic hepatitis due to hepatitis B virus, hereditary hemochromatosis and primary sclerosing cholangitis. In some embodiments, the PNPLA3 polymorphism is used to predict the progression of liver disease. In certain modalities where the patient's condition does not improve, according to the doctor's discretion, the administration of the compounds is administered chronically, that is, over a prolonged period of time, even throughout the patient's life to improve. or otherwise control or limit the symptoms of the patient's disease or condition. In certain embodiments where a patient's condition improves, the dose of the drug being administered is temporarily reduced or temporarily discontinued for a certain period of time (i.e., a "drug break"). In specific embodiments, the duration drug break is between 2 days and 1 year, including by way of example only, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, days, 20 days, 28 days or more than 28 days The dose reduction during a drug rest period is, for example, 10% to 100%, including, but not limited to, only 10%, 15%. 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% and 100% . Once there has been improvement in the patient's condition, a maintenance dose is administered if necessary. Subsequently, in specific embodiments, the dosage or frequency of administration, or both, is reduced, based on symptoms, to a level where the improved disease, disorder or condition is preserved. In certain modalities, however, the patient requires long-term intermittent or daily treatment for any recurrence of symptoms. The amount of a given agent that corresponds to such an amount varies depending on factors such as the particular compound, the condition of the disease and its severity, the identity (e.g., weight, sex) of the subject or host needing treatment, but nevertheless determined according to the particular circumstances surrounding the case, including, for example, the specific agent being administered, the route of administration, the condition being treated, and the subject or host being treated. In general, however, doses used for the treatment of adult humans are typically in the range of 0.01 mg to 5000 mg per day. In one aspect, doses used for the treatment of adult humans are from about 1 mg to about 1000 mg per day. In one embodiment, the desired dose is conveniently presented in a single dose or in divided doses administered simultaneously or at appropriate intervals, for example as two, three, four or more subdoses per day. In one embodiment, appropriate daily doses for the compound described herein, or a pharmaceutically acceptable salt thereof, are from about 0.01 to about 50 mg / kg by body weight. In some embodiments, the daily dosage or amount of active substance in the dosage form is lower or higher than the ranges set forth herein, depending on a number of variables with respect to an individual treatment regimen. In various embodiments, the daily and unit doses are modified depending on a number of variables including, but not limited to, the activity of the compound used, the disease or condition to be treated, the mode of administration, the requirements of the individual subject, the severity of the disease or condition being treated and the physician's judgment. The toxicity and therapeutic efficacy of such therapeutic regimens are determined by standard pharmaceutical procedures in cell cultures or experimental animals, including, but not limited to, determination of LD10 and ED90. The dose relationship between toxic and therapeutic effects is the therapeutic index and is expressed as the ratio between LD50 and ED50. In certain embodiments, data obtained from cell culture assays and animal studies are used to formulate the therapeutically effective daily dosage range and / or the therapeutically effective unit dosage amount for use in mammals, including humans. In some embodiments, the daily dosage amount of the compounds described herein is within a range of circulating concentrations that include the ED50 with minimal toxicity. In certain embodiments, the daily dosage range and / or unit dosage amount varies within this range depending on the dosage form employed and the route of administration used. oonRhn / cznz / a / υιλι In any of the aforementioned aspects there are additional embodiments wherein the effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, is: (a) administered systemically to the mammal; and / or (b) administered orally to the mammal; and / or (c) administered intravenously to the mammal; and / or (d) administered by injection to the mammal; and / or (e) topically administered to the mammal; and / or (f) administered non-systemically or locally to the mammal. In any of the aforementioned aspects there are additional embodiments comprising single administrations of the effective amount of the compound, including additional embodiments wherein (i) the compound is administered once a day; or (II) the compound is administered to the mammal several times over the course of a day. In any of the aforementioned aspects there are additional embodiments comprising multiple administrations of the effective amount of the compound, including additional embodiments wherein (i) the compound is administered continuously or intermittently: as in a single dose; (i) the time between multiple administrations is every 6 hours; (iii) the compound is administered to the mammal every 8 hours; (iv) the compound is administered to the subject every 12 hours; (v) the compound is administered to the subject every 24 hours. In additional or alternative embodiments, the method comprises a drug break, wherein administration of the compound is temporarily suspended or the dose of the compound being administered is temporarily reduced; At the end of the drug break, dosing of the compound is resumed. In one embodiment, the duration of the drug break ranges from 2 days to 1 year. Administration routes Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ophthalmic, pulmonary, transmucosal, transdermal, vaginal, otic, nasal and topical administration. Furthermore, by way of example only, parenteral administration includes intramuscular, subcutaneous, intravenous and intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic and intranasal injections. In certain embodiments, a compound as described herein is administered locally rather than systemically, for example, by injection of the compound directly into an organ, often in a depot preparation or a sustained release formulation. In specific embodiments, the long-acting formulations are administered by implantation (e.g., subcutaneously or intramuscularly) or by intramuscular injection. Furthermore, in other embodiments, the drug is administered in a targeted drug delivery system, for example, in a liposome coated with an organ-specific antibody. In such embodiments, the liposomes are targeted to the oonRhn / cznz / a / υιλι organ and are selectively absorbed by it. In still other embodiments, the compound as described herein is provided in the form of a rapid release formulation, in the form of a sustained release formulation or in the form of an intermediate release formulation. In still other embodiments, the compound described herein is administered topically. Pharmaceutical Compositions / Formulations The compounds described herein are administered to a subject in need, either alone or in combination with pharmaceutically acceptable carriers, excipients or diluents, in a pharmaceutical composition, in accordance with standard pharmaceutical practice. In one embodiment, the compounds of this invention can be administered to animals. The compounds may be administered orally or parenterally, including intravenous, intramuscular, intraperitoneal, subcutaneous, rectal, and topical routes of administration. In another aspect, provided herein are pharmaceutical compositions comprising a compound described herein, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, and at least one pharmaceutically acceptable excipient. Pharmaceutical compositions are conventionally formulated using one or more pharmaceutically acceptable excipients that facilitate processing of the active compounds into pharmaceutically usable preparations. The appropriate formulation depends on the chosen route of administration. A summary of the pharmaceutical compositions described herein can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Edition (Easton, Pennsylvania: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H. A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th ed. (Lippincott Williams & Wilkins 1999), incorporated herein by reference for such disclosure. In some embodiments, the pharmaceutically acceptable excipient is selected from carriers, binders, fillers, suspending agents, flavoring agents, sweetening agents, disintegrating agents, dispersing agents, surfactants, lubricants, colorants, diluents, solubilizers, wetting agents, plasticizers, stabilizers, penetration enhancers, wetting agents, antifoaming agents, antioxidants, preservatives and any combination thereof. The pharmaceutical compositions described herein are administered to a subject by appropriate routes of administration, including, but not limited to, oral, parenteral (e.g., intravenous, subcutaneous, intramuscular), oonRhn / cznz / a / υιλι intranasal routes of administration. , oral, topical, rectal or transdermal. The pharmaceutical formulations described herein include, but are not limited to, aqueous liquid dispersions, liquids, gels, syrups, elixirs, sludges, suspensions, self-emulsifying dispersions, solid solutions, liposomal dispersions, aerosols, solid oral dosage forms, powders, release formulations , controlled release formulations, fast melting formulations, tablets, capsules, pills, powders, dragees, effervescent formulations, lyophilized formulations, delayed release formulations, sustained release formulations, pulsatile release formulations, multiparticulate formulations and mixed immediate release formulations and controlled. Pharmaceutical compositions including compounds described herein, or one of their pharmaceutically acceptable salts, solvates or stereoisomers are manufactured in a conventional manner, such as, by way of example only, by mixing, dissolving, granulation, drageing, levigation, emulsification, encapsulation, entrapment or compression processes. Pharmaceutical compositions for oral use are obtained by mixing one or more solid excipients with one or more of the compounds described herein, optionally crushing the resulting mixture and processing the mixture of granules, after adding appropriate auxiliaries, if desired, to obtain tablets. or dragees, cores. Suitable excipients include, for example, fillers such as sugars, including lactose, sucrose, mannitol or sorbitol; cellulose preparations such as, for example, corn starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose; or others such as polyvinylpyrrolidone (PVP or povidone) or calcium phosphate. If desired, disintegrating agents are added, such as cross-linked croscarmellose sodium, polyvinylpyrrolidone, agar or alginic acid or a salt thereof such as sodium alginate. In some embodiments, colorants or pigments are added to tablets or dragee coatings for identification or to characterize different combinations of doses of active compound. Pharmaceutical compositions that are administered orally include snap-fit ​​capsules made of gelatin, as well as sealed soft capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Snap-fit ​​capsules contain the active ingredients mixed with fillers such as lactose, binders such as starches and / or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds are dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin or liquid polyethylene glycols. In some embodiments, stabilizers are added. Pharmaceutical compositions for parental use are formulated as infusions or oonRhn / cznz / a / υιλι injections. In some embodiments, the pharmaceutical composition suitable for injection or infusion includes sterile aqueous solutions or dispersions or sterile powders comprising a compound described herein, or one of its pharmaceutically acceptable salts, solvates or stereoisomers. In some embodiments, the pharmaceutical composition comprises a liquid carrier. In some embodiments, the liquid carrier is a solvent or liquid dispersion medium comprising, for example, water, saline, ethanol, a polyol (e.g., glycerol, propylene glycol, liquid polyethylene glycols and the like), vegetable oils, non-toxic glycerol esters, and any combination thereof. In some embodiments, the pharmaceutical compositions further comprise a preservative to prevent the growth of microorganisms. Combination Described herein are methods of treating a liver disease, a metabolic disease or a cardiovascular disease using a compound described herein, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, in combination with an additional therapeutic agent. In some embodiments, the additional therapeutic agent is used for the treatment of diabetes or diabetes-related disorders or conditions. In some cases, the additional therapeutic agent comprises a statin, an insulin-sensitizing drug, an insulin secretagogue, an alpha-glucosidase inhibitor, a GLP agonist, a GIP agonist, a THR beta agonist, a PDE inhibitor , a DPP-4 inhibitor (such as sitagliptin, vildagliptin, saxagliptin, linagliptin, anagliptin, teneligliptin, alogliptin, gemigliptin, or dutogliptin), a catecholamine (such as epinephrine, norepinephrine, or dopamine), peroxisome proliferator-activated receptor (PPAR) gamma agonist ) (for example, a thiazolidinedione (TZD) [such as pioglitazone, rosiglitazone, rivoglitazone, or troglitazone], aleglitazar, farglitazar, muraglitazar, or tesaglitazar), peroxisome proliferator-activated receptor (PPAR) alpha agonist, peroxisome proliferator-activated delta receptor (PPAR) agonist, a farnesoid X receptor (FXR) agonist (e.g., obeticholic acid), or a combination thereof. In some cases, the statin is an HMG-CoA reductase inhibitor. In other cases, additional therapeutic agents include fish oil, fibrate, vitamins such as niacin, retinoic acid (e.g., 9 cis-retinoic acid), nicotinamide ribonucleoside or analogues thereof, or combinations thereof. In other cases, additional therapeutic agents include OAC inhibitors, FGF19 and FGF21 mimetics, CCR2 / CCR5 antagonists, or combinations thereof. In some embodiments, the additional therapeutic agent is vivitrol. In some embodiments, the additional therapeutic agent is a statin such as an oonRhn / cznz / a / υιλι HMG-CoA reductase inhibitor, fish oil, fibrate, niacin, or a combination thereof. In other cases, the additional therapeutic agent is a dyslipidemia drug that prevents lipid absorption, such as orlistat. In some embodiments, the additional therapeutic agent is a vitamin such as retinoic acid or tocopheryl acetate for the treatment of diabetes and diabetes-related disorders or conditions, such as reducing elevated body weight and / or reducing blood glucose. elevated by food intake. In some embodiments, the additional therapeutic agent is a hypoglycemic agent. In some embodiments, the additional therapeutic agent is an anti-obesity agent. In some embodiments, the additional therapeutic agent is selected from a peroxisome proliferator-activated receptor (PPAR) agonist (gamma, dual or pan), a dipeptidyl peptidase (IV) inhibitor, a glucagon-like peptide-1 (GLP -I) analogue, insulin or an insulin analogue, an insulin secretagogue, an inhibitor of sodium glucose cotransporter 2 (SGLT2), a glucophage, a human amylin analogue, a biguanide, an alpha-glucosidase inhibitor, a meglitinide, a thiazolidinedione and a sulfonylurea. In some embodiments, the additional therapeutic agent is metformin, sitagliptin, saxaglitpin, replinide, nateglinide, exenatide, liraglutide, insulin lispro, insulin aspart, insulin glargine, insulin detemir, insulin isophane and glucagon-like peptide-1, or any combination thereof. themselves. In some embodiments, the additional therapeutic agent is a lipid-lowering agent. In some embodiments, the additional therapeutic agent is an antioxidant, a corticosteroid such as budesonide, anti-tumor necrosis factor (TNF), or a combination thereof. In some embodiments, the additional therapeutic agent is administered at the same time as the compound described herein. In some embodiments, the additional therapeutic agent and the compound described herein are administered sequentially. In some embodiments, the additional therapeutic agent is administered less frequently than the compound described herein. In some embodiments, the additional therapeutic agent is administered more frequently than the compound described herein. In some embodiments, the additional therapeutic agent is administered prior to administration of the compound described herein. In some embodiments, the additional therapeutic agent is administered after administration of the compound described herein. oonRhn / cznz / a / υιλι F·' O ::rc .-5....-1-0 LX NH- ..A. ...TO .... i 1 ? ' [ 'J N i: Tnethylorthoformate ----μη 1U0 -C 12 ir Step 1 CH. . Yo HCl in dioxane. NH.· 3140 C 2 hr A 5...... ► i IJI 1 + oonRhn / cznz / a / υιλι EXAMPLES Example 1: Synthesis of N-(3-benzyl-4-oxo-3,4-dihydroqunazolin-5-l)-3,5-dichloro-4hydroxybenzamide? 1-----1j Η. N '3' - 0’ NH 3 l._ J f’d I JΊ| ... aritplrjs 1 4 dioxane,f. 1Ώ0 3. Go Step 2 ΊΓOHo i :'Ί - 4 : r y ?...... Chlorobenzene ’3H · r · N । - Step 3 V-n'-' X· 130’0 121+ Cl1 Step 4 Step 1: Synthesis of 3-benzyl-5-bromoquinazolin-4(3H)-one To a suspension of 5-bromo-2,4-dihydro-1H-3,1-benzoxazíne-2,4-dione (5.00 g, 20.7 mmol) in trimethyl orthoformate (12.0 ml) was added benzylamine (2.66 g , 24.8 mmol) at room temperature and then heated to 100 °C for 12 h. Once the reaction was complete, the reaction mixture was poured into ice water (70 ml) and extracted with ethyl acetate (2x250 ml). The combined organic extracts were washed with brine solution (70 ml) and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography using 20 ethyl acetate. % in hexane as eluent to produce 3-benzyl-5-bromoquinazolin-4(3 / - / )-one (4.50 g, 69%) as an off-white solid. LCMS (ES) m / z cale, for C15H11BrN2O, 314.01; found, 315.0 (M+H). Step 2: Synthesis of tert-butyl (3-benzyl-4-oxo-3,4-dihydroquinazolin-5-yl)carbamate To a stirred solution of 3-benzyl-5-bromo-3,4-dihydroquinazolin-4-one (4.70 g, 14.9 mmol) in 1,4-dioxane (30.0 ml) was added carbamate of tere-butyl (2.62 g, 22.4 mmol) and cesium carbonate (9.72 g, 29.8 mmol), the mixture was degassed under a nitrogen atmosphere for 10 minutes. To this, Xantphos (1.73 g, 2.98 mmol), Pd(dba)2 (858 mg, 1.49 mmol) was added and then heated at 100 °C for 16 h. After completion of the reaction, the reaction mixture was filtered through a pad of celite and washed with ethyl acetate (50 ml). The filtrate was washed with brine solution (70 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography to give tert-butyl (3- Benzyl-4-oxo-3,4-dihydroquinazolin-5¡l)carbamate (5.00 g, 95.41%) as a yellow solid. LCMS (ES) m / z cale. For C20H21N3O3, 351.16; found, 352.2 (M+H). Step 3: Synthesis of 5-amino-3-benzylkynazolin-4(3H)-one To a suspended solution of tert-butyl N-(3-benzyl-4-oxo-3,4-dihydroquinazolin-5yl)carbamate (5.24 g, 14.9 mmol) in 1,4-dioxane was added 4 M HCl in dioxane (5.18 ml, 149 mmol) at 0 °C. The resulting reaction mixture was heated at 80 °C for 1 h. After completion of the reaction, the reaction mixture was concentrated under reduced vacuum to give a crude solid which was triturated with diethyl ether (100 ml) to give 5-amino-3-benzylquinazolin-4(3H)-one (3.50 g, 93%, crude) as a yellow solid. LCMS (ES) m / zcale. For C15H13N3O, 251.11; found, 252.1 (M+H). Step 4: Synthesis of N-(3-benzyl-4-oxo-3,4-dihydroquinazolin-5-yl)-3,5-dichloro-4hydroxybenzamide To a stirred solution of 5-amino-3-benzyl-3,4-dihydroquinazolin-4-one (0.2 g, 0.796 mmol) and 3,5-dichloro-4-hydroxybenzo acid phosphorus trichloride (0.7 ml, 0.796 mmol) was added at 0 °C. The resulting reaction mixture was heated at 130 °C for 12 h. Once the reaction was complete, the reaction mixture was quenched with ice water (30 ml) under stirring for 5 minutes. The solid obtained was collected by filtration. The solid was washed with acetonitrile (15 mL), diethyl ether (15 mL) and dried under vacuum to give crude material. The crude material was purified by preparative HPLC to provide A / -(3-benzyl-4-oxo-3,4-dihydroquinazolin-5-íl)-3,5-dichloro- 4-Hydroxybenzamide (0.025 g, 7%) as an off-white solid LCMS (ES) m / zkale. For C22H15CI2N3O3,439.05; found, 440.1 (M+H);1H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1 H), 11.17 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.61 (s , 1H), 7.85 (m, 3H), 7.35 (m, 5H), 5.26 (s, 2H). Example 2: Synthesis of 3,5-dichloro-4-hydroxy¡-N-(4-oxo-3-(2-(trifluoromethoxy)benzyl)3,4-dihydroquinazolin-5-yl)benzamide oonRhn / cznz / a / υιλιF>. Jl Trimethyl ortho format MU JJAl Ziri_- [(.. J1iodine ethanol '' MnOH ilOCIÍih . -' Step 1 i Step 2 A. 1 ... . 1 L' ' ' ... Ί Ϊ Ϊ •vi acn - ií I í ..i '. --..h - '' Step 3 Step 1: Synthesis of 5-nitro-3-(2-(trifluoromethoxy)benzyl)quinazolin-4(3H)-one To a stirred solution of 1-[2-(tnfluoromethoxy)phenyl]methanamine (3.00 g, 15.7 mmol) in ethanol (25.0 mL) was added 2-amino-6-nitrobenzoic acid (2.86 g, 15.7 mmol). , tñmethoxymethane (3.74 mL, 31.4 mmol) and iodine (0.2 g, 1.57 mmol) at room temperature. The resulting reaction mixture was heated at 80 °C for 16 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to give a crude residue which was purified by flash chromatography to produce 5-nitro-3-{[2-(trifluoromethoxy)phenyl]methyl}-3,4dihydroquinazoline- 4-one as a yellow solid (2.1 g, 37% yield). LCMS (ES) m / z calc.C16H10F3N3O4, 365.06; found, 366.1 (M+H). Step 2: Synthesis of 5-amino-3-(2-(trifluoromethoxy)benzyl)quinazolin-4(3H)-one: To a stirred solution of 5-nitro-3-{[2-(trifluoromethoxy)phenyl]methyl}-3,4-dihydroquinazolin4-one (2.10 g, 5.75 mmol) in methanol: water: tetrahydrofuran ( 1:1:4) (40.0 ml) ammonium acetate (4.43 g, 57.5 mmol) and zinc powder (3.76 g, 57.5 mmol) were added at room temperature and then stirred for 1 h. After completion of the reaction, the reaction mixture was filtered through a pad of celite and washed with ethyl acetate (50 ml). The filtrate was washed with water (20 ml_), brine (20 ml_), dried over sodium sulfate and evaporated under reduced pressure to give a crude residue which was purified by flash chromatography to give 5amino-3-{[2 -(tñfluoromethoxy)phen¡l]methyl}-3,4-d¡hydroqu¡nazolin-4-one (1.29 g, 3.85 mmol) as an off-white solid (1.29 g, 67% yield). LCMS (ES) m / z cale. C16H12F3N3O2, 335.09; found, 336.1 (M+H). Step 3: Synthesis of 3,5-dichloro-4-hydroxy-N-(4-oxo-3-(2-(trifluoromethoxy)benzyl)-3,4dihydroquinazolin-5-yl)benzamide To a stirred solution of 5-amino-3-{[2-(tnfluoromethoxy)phenyl]methyl}-3,4dihydroquinazolin-4-one (0.2 g, 597 pmol) in chlorobenzene (2.00 ml) added 3,5 dichloro-4-hydroxybenzoic acid (0.12 g, 0.597 mmol) and Phosphorus trichloride (0.7 mL, 0.796 mmol) at 0 °C. The resulting reaction mixture was heated at 130 °C for 6 h. Once the reaction was complete, the reaction mixture was quenched with ice water (30 ml) with stirring for 5 minutes. The solid obtained was collected by filtration. The solid was washed with methanol (15 ml), pentane (15 ml) and dried under vacuum to yield 3,5-dichloro-4-hydroxy¡-N-(4-oxo-3-{[2(trifluoromethoxy )phen¡l]methyl}-3,4-d¡hydroqu¡nazol¡n-5-¡l)benzamide as a brown solid (0.14 g, 45%). LCMS (ES) m / z cale. C23H14CI2F3N3O4, 523.03; found, 524.1(M+H).1H NMR (400 MHz, DMSO d6) δ 12.85 (s, 1H), 11.14 (s, 1H), 8.71 (d, J= 8.0 Hz, 1H), 8.57 (s, 1H) ), 7.8 (t, J = 8.4 Hz, 3H), 7.49 - 7.37 (m, 5H), 5.35 (s, 2H). oonRhn / cznz / a / υιλι Example 3: Synthesis of 3,5-dichloro-N-(3-(cyclopropylmethyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4-hydroxybenzamide Trimethyl orthoformate f.J1.,,·· νη^Λγ, powder ZrTV'=,1. ^ ·'|,CH lt,JL 1,’h1 hf Water \lron-i i 11 Step 1 :·- ’ i' । · Step 2 -X .. ,.D i’;:i Chlorobenzene ' L J J l'J j'C 2 h Step 3 Step 1: Synthesis of 3-(cyclopropylmethyl)-5-nitroquinazolin-4(3H)-one To a stirred solution of 2-amino-6-nitrobenzoic acid (3.00 g, 16.5 mmol) and cyclopropylmethanamine (1.52 g, 21.4 mmol) in ethanol (15.0 ml) was added iodine (0.209 g, 1.65 mmol) and trimethyl orthoformate ( 3.64 ml, 32.9 mmol) in a sealed tube and the reaction mixture was stirred at 100 °C for 16 h. After the reaction was completed, the reaction mass was cooled to room temperature, the reaction mass was concentrated in vacuo. The crude material was purified by flash column chromatography as eluent to obtain 3-(cyclopropylmethyl)-5nitroquinazolin-4(3H)-one (2.50 g, 62%) as a yellow gummy solid. LCMS (ES) m / z calculated. forC12H11N3O3, 245.24; found 246.1 (M+H). Step 2: Synthesis of 5-amino-3-(cyclopropylmethyl)quinazoline-4(3H)-one. To a stirred solution of 3-(cyclopropylmethyl)-5-nitroquinazolin-4(3 / - / )-one (2.50 g, 10.2 mmol) in tetrahydrofuran: methanol: Water (4:1:1) (25.0 ml) Zinc powder (6.66 g, 102 mmol) and ammonium acetate (7.86 g, 102 mmol) were added at 0 °C and allowed to stir slowly at room temperature for 1 h. After completing the reaction, the reaction mass was filtered through a bed of celite and washed with 50% methanol in dichloromethane (100 ml), the filtrate obtained was concentrated in vacuo to give a crude residue. The residue was dissolved in 10% methanol in dichloromethane and washed with ice water (50ml), dried anhydrous sodium sulfate, filtered and evaporated under vacuum to give 5-amino-3-(cyclopropylmethyl)quinazoline. -4(3 / - / )-one (2.00 g, 91%) as an off-white solid. LCMS (ES) m / z calculated for C12H13N3O, 215.26; found 216.2 (M+H). Step 3: Synthesis of 3,5-dichloro- / V-(3-(cyclopropylmethyl)-4-oxo-3,4-dihydroquinazolin5-íl)-4-hydroxybenzamide To a stirred solution of 5-amino-3-(cyclopropylmethyl)quinazolin-4(3H)-one (0.150 g, 0.697 mmol) in chlorobenzene (5.0 ml) was added 3,5-dichloro-4-hydroxy acid benzoic acid (0.144 g, 0.697 mmol) and phosphorus trichloride (0.03 mL, 0.348 mmol) at 0 °C. The resulting reaction mixture was heated at 130 °C for 2 h. Once the reaction was complete, the oonRhn / cznz / a / υιλι reaction mixture was quenched with ice water (30 ml) with stirring for 5 minutes. The solid obtained was collected by filtration. The crude solid was purified by preparative HPLC to provide 3,5-dichloro-N-(3-(cyclopropylmethyl)-4-oxo-3,4-dihydroquinazoline-5 -!l)-4hydroxybenzamide) (0.025 g, 8.87%) as a white solid. LCMS (ES) m / z cale, for C19H15CI2N3O3, 403.25; found 404.0 (M+1H).1H-NMR (400 MHz, DMSO-d6): δ 13.09 (s, 1H), 11.16 (br, 1H), 8.73-8.71 (m, 1H), 8.50 (s, 1H) , 7.94 (s, 2H), 7.85 (t, J=8.4 Hz, 1H), 7.437.41 (m, 1H), 3.92 (d, J=7.2 Hz, 2H), 1.37-1.31 (m, 1H), 0.57-0.45(m, 4H). Example 4: Synthesis of 3,5-dichloro-4-hydroxy- / \ / -(3-((2-hydroxypyrídin-4-yl)methyl)-4oxo-3,4-dihydroquinazolín-5-¡ l)benzamide;í·...,.,1.,,....... J I. U L .1. ,J l1,, ·1. NHjOAci Zn powder ] ] j J ] Tnmethyl orthoformate. 'IHIVeCl· Water' I I tOH 8(T C -1 hrt!h PCI;. ACN. 120:C <- .. h Step 3 Step 1: Synthesis of 3-[(2-methoxypyridin-4-yl)methyl]-5-nitro-3,4-dihydroquinazolin-4one To a stirred solution of 2-amino-6-nitrobenzoic acid (1.00 g, 5.49 mmol), 1-(2methoxypyridín-4-íl)methanamine (0.766 ml_, 5.49 mmol) and trimethoxymethane (12.0 ml_, 110 mmol) in ethanol (10.0 mL), iodine (69.7 mg, 0.549 mmol) was added and heated at 80 °C for 4 h. After the reaction was completed, the reaction mass was cooled to room temperature and concentrated in vacuo to obtain the crude product, the crude product was diluted with ethyl acetate (100 ml) and stirred for 5 minutes, the solid was collected. by filtration and dried in vacuo to produce 3-[(2-methoxy¡pyridin-4-yl)methyl]-5-nitro-3,4-dihydroqunazolín- 4-one (680 mg, 40%) as an off-white solid. LCMS (ES) m / z cale, for C15H12N4O4, 312.0; found 313.0 (M+1H). Step 2: synthesis of 5-amino-3-((2-methoxypyridin-4-yl)methyl)quinazolin-4(3H)-one To a stirred solution of 3-[(2-methoxypyridín-4-yl)methyl]-5-nitro-3,4-dihydroquinazolin-4one (680 mg, 2.18 mmol) in THF: Water: MeOH (8:1:1) ammonium acetate (1.68 g, 21.8 mmol), zinc (1.42 g, 21.8 mmol) was added and then stirred at room temperature for 1 h. After completion of the reaction, the reaction mass was filtered through a pad of celite and washed with MeOH (10 ml), the filtrate was concentrated in vacuo to give a crude residue which was purified by flash column chromatography to give 5-amino-3-[(2-methoxy¡pindin-4¡l)methyl]-3,4-d¡hydroquinazolin-4-one (600 mg, 98%) as an off-white solid. LCMS (ES) m / zcalc. for C15H14N4O2, 282.1; found 283 (M+1H). Step 3: Synthesis of 3,5-dichloro-4-hydroxy-N-(3-((2-hydroxy¡pyridn-4-yl)methyl)-4-oxo3,4-dihydroquinazoline -5-yl)benzamide To a stirred solution of 5-amino-3-[(2-methoxy¡pindin-4-¡l)methyl]-3,4-dihydroqunazolín-4one (300 mg, 1.06 mmol) in acetonitrile (4.00 ml), 3, 5-dichloro-4-hydroxybenzoic acid (220 mg, 1.06 mmol), phosphorus trichloride (0.726 ml, 0.744 mmol) were added and heated to 120 °C for 3 h. Once the reaction was complete, the reaction mixture was cooled to room temperature and quenched with ice water (10 ml) and extracted with ethyl acetate (2x20 ml). The combined organic extracts were washed with brine (10 ml) and dried over sodium sulfate, filtered and concentrated under vacuum to obtain crude material. The crude compound was purified by preparative HPLC to provide 3,5-dichloro-4-hydroxyl-N-{3-[(2-hydroxypyridin-4l)methyl]-4-oxo-3 ,4-d¡hydroqu¡nazol¡n-5-¡l}benzamide (29.0 mg, 5.97%) as an off-white solid. LCMS (ES) m / z cale. C21H14CI2N4O4, 456.0; found, 455.0 (M-1H).1H NMR (400 MHz, DMSO d6): δ 12.66 (s, 1H), 11.55 (br, 1H), 8.75 (d, J=8 Hz, 1 H), 8.50 (s , 1H), 7.797.86 (m, 3H), 7.34-7.40 (m, 2 H), 7.09 (br, 1 H), 6.10-6.16 (m, 2 H), 5.11 (s, 2 H). The following compounds were synthesized as described in Example 2. oonRhn / cznz / a / υιλι E¡· Spectral data 5 LCMS (ES) m / z cale, for C23H17CI2N3O4, 469.06; found, 470.1 (M+H); 1H NMR (400 MHz, DMSO-cfeo 12.96(s, 1H), 11.16 (s, 1H), 8.67 (d, J=8 Hz,1H), 8.49 (s, 1H), 7.87-7.81 (m, 3H) , 7.41 (d. J = 8 Hz,1H), 7.29 (t, J =7.6 Hz, 1H), 7.16 (d, J =7.6 Hz,1 H), 7.03 (d, J=8.4 Hz,1 H) , 6.90 (t, J =7.2 Hz, 1H), 5.17 (s, 2H), 3.83 (s, 3H). 6 LCMS (ES) m / zcalc. 1H NMR (400 MHz, DMSO-d6) δ 12.48 (s, 1H), 8.74 (d, J= 8.4 Hz, 1 H), 8.56 (s, 1 H), 7,787.70 (m, 3H), 7.63 ( s, 1H), 7.57 (d, J = 8 Hz, 2H), 7.29 (d, J =8 Hz, 1H), 7.06 (s, 1H), 5.35 (s, 2H). zcalc. for C22H14CI2FN3O3, 457.04; found, 458.1 (M+H); Hz,1 H), 8.61 (s, 1H), 7.88-7.82 (m, 3H), 7.47-7.40 (m, 3H), 7.20-7.15 (m, 2H), 5.24 (s, 2H). ES) m / zcalc. for C23H14CI2F3N3O4, found, 524.0 (M+H); 1H NMR (400 MHz, DMSO-ofe) δ 12.90 (s, 1H), 11.17 (s, 1H), 8.71 (d, J =7.6 Hz, 1H), 8.64 (s, 1H), 7.90-7.85 (m, 3H), 7.54 (d, J= 8.8 Hz, 2H), 7.44 (d, J= 7.6 Hz,1H), 7.37 (d , J = 8 Hz, 2H), 5.32 (s, 2H). 9 LCMS (ES): m / z cale, for C22H14CI2FN3O3 457.04; found, 458.1 (M+H); 1H NMR (400 MHz, DMSO d6): δ 12.89 (s, 1H), 11.15 (s, 1H), 8.69 (d, J = 7.6 Hz, 1H), 8.59 (s, 1H), 7.89-7.85 (m , 3H), 7.45-7.33 (m, 3H), 7.27-7.17 (m, 2H) and 5.33 (s, 2H). 10 LCMS (ES) m / zcalc. for C23H14CI2F3N3O4, 523.03; found 523.8 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 12.90 (s, 1H), 11.17 (br, 1H), 8.64-8.69 (m, 2H), 7.877.82 (m, 3H), 7.48-7.38 (m, 3H), 7.31 (d, J=7.6 Hz,1H), 5.29 (s,2H). 11 LCMS (ES) m / zcalc. C23H14CI2F3N3O3, 507.04; found, 508.0 (M+H); 1H NMR (400 MHz, DMSO d6) δ 12.75 (s, 1H), 11.20 (s, 1H), 8.73 (d, J = 8.4 Hz, 1H), 8.67(s, 1H), 7.88 - 7.81 (m, 4H ), 7.70 (t, J = 8.0 Hz, 2H), 7.61 (t, J = 7.6 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 5.36 (s, 2H). 12 LCMS (ES) m / zcalc. C23H16CI2FN3O3, 471.06; found, 472.0 (M+H); 1H NMR AND. Spectral data (400 MHz, DMSO efe) δ 12.98 (s, 1H), 11.16 (s, 1H), 8.72 (d, J= 8.0 Hz, 1H), 8.46 (s, 1H), 7.86 (t, J = 8.0 Hz, 3H), 7.46 - 7.41 (m, 2H), 7.34 (d, J = 10.4 Hz, 1H), 7.26 (d, J = 7.6 Hz, 1H), 7.19-7.15 (m, 1H), 6.23-6.18 (m, 1H), 1.89 (d, J= 7.2 Hz, 3H). 13 LCMS (ES) m / z cale, for C21H13CI2FN4O3, 458.03; found, 459.0, (M+H). 1H NMR (400 MHz, DMSO-d6) δ 12.74 (s, 1H), 11.22 (s, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.58 (d, J = 2.4 Hz, 2H), 8.36 (d, J = 4.8 Hz, 1H), 7.91 -7.83 (m, 3H), 7.43 (d, J = 7.6 Hz, 1H), 7.31 (t, J=6.4 Hz, 1H), 5.35 (s, 2H) . 14 LCMS (ES) m / z calo, for C18H11CI2N5O3S, 447.0; found, 448.0 (M+H); 1H NMR (400 MHz, DMSO-cfc): δ 12.77 (s, 1 H), 11.25 (br, 1H), 9.62 (s, 1 H), 8.72 (d, J=8.4 Hz, 1 H), 8.67 ( s, 1 H), 7.88-7.92 (m, 3 H), 7.47 (d, J= 7.6 Hz, 1H), 5.79 (s, 2H). 15 LCMS (ES) m / z cale, for C19H12CI2N4O4, 430.02; found, 431.02 (M+H); 1H NMR (400 MHz, DMSO-di,): δ 12.86 (s, 1 H), 11.17 (br, 1H), 8.70 (d, J = 8 Hz, 1 H), 8.54 (s, 1 H), 8.35 (s, 1 H), 8.17 (s, 1H), 7.88-7.82 (m, 2 H), 7.40 (d, J = 8.4 Hz, 1H), 5.19 (s, 2 H). 16 LCMS (ES) m / z cale. C22H14CI2FN3O3, 457.04; found, 458.1[M + H]+;1H NMR (400 MHz, DMSO-cfc) 5 12.89 (s, 1H), 11.1 (s, 1H), 8.68 (d, J= 7.6 Hz, 1H), 8.60 (s , 1H), 7.88 - 7.82 (m, 3H), 7.41 - 7.37 (m, 2H), 7.25 (d, J= 9.6 Hz, 2H), 7.15 - 7.10 (m, 1H), 5.27 (s, 2H). 17 LCMS (ES) m / zcale. C23H15CI2F3N4O5, 554.04; found, 439.0 [M + H]+; 1H NMR (400 MHz, DMSO-cfe) 511. 14(s, 1H), 8.72 (d, J = 8.0 Hz, 1 H), 8.59 (t, J = 4.0 Hz, 3H), 7.91 - 7.87 (m, 3H), 7.48 - 7.43 (m, 3H), 5.36(s, 2H). 18 LCMS (ES) m / z cale, for C23H14CI2F3N3O3 507.2; found, 508.1 (M+H); 1H NMR (400 MHz, DMSO Ó6): δ 12.9 (s, 1H), 11.13 (br, 1H), 8.72 - 8.70 (m, 1H), 8.57 (s, 1H), 8.92 - 7.81 (m, 4H) , 7.63 - 7.59 (m, 1H), 7.55 - 7.48 (m, 2H), 7.15 (d, J = 7.6 Hz, 1H), 5.48 (s, 2H). 19 LCMS (ES) m / z cale, for C22H13CI2F3N4O3, 508.03; found 509.0 (M+H); 1HNMR (400 MHz, DMSO-d6): δ 12.83 (s, 1H), 11.15 (br, 1H), 8.89(s, 1H), 8.71 (s, 1H), 8.68 (s, 1H), 8.10 (dd , J=1.6 Hz, 1H), 7.91 -7.85 (m, 4H), 7.46-7.44 (m, 1H), 5.42 (s, 2H). Example 20: Synthesis of 3,5-dichloro-4-hydroxy- / V-(4-oxo-3-(1-phenylcyclopropyl)-3,4dihydroquinazolin-5-yl)benzamide I. ...I. HATU DIPEA DMF. RT 4pm Step 1 rni. or ► Zn Powder Nlt4CI 'Iri III· H 0 MeüH ·.Υ-,χ' Rl:ih Step 3 PCI;PhCI >: c .3 h Step 4 CuiOAr.i- Im PhCI IH h Step 2 C.U. Step 1: Synthesis of 2-amino-6-nitro-W-(1-phenylcyclopropyl)benzamide To a stirred solution of 2-amino-6-nitrobenzoic acid (0.5 g, 2.74 mmol) and 1-phenylcyclopropan-1-amine (658 mg, 3.02 mmol) in DMF (5 ml) were added HATU (2.09 g, 4.11 100 mmol) and DIPEA (0.956 ml, 8.22 mmol) at 0 °C. The resulting reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, the reaction mixture was quenched with ice-water, the precipitated solids were filtered and washed with n-hexanes, dried under vacuum to provide 2-amino-6-nitro-N-(1-phenylcyclopropyl) benzamide as a beige solid (0.620 g, 69%) LCMS (ES) m / z calculated for C16H15N3O3, 297.1; found 298.1 [M+H] + . Step 2: Synthesis of 5-nitro-3-(1-phenyl cyclopropyl) quinazoline-4(3 / 7)-one In a sealed tube, to a stirred solution of 2-amino-6-nitro-N-(1-phenylcyclopropyl) benzamide (0.62 g, 2.08 mmol) in chlorobenzene (13 ml) was added copper acetate (0.05 mg, 0.2 mmol ), trimethylorthoformate (2.28 ml, 20.8 mmol) and imidazole (0.42 g, 3.12 mmol). The resulting reaction mixture was stirred for 48 h at 150 °C. After completion of the reaction, the reaction mixture was evaporated in vacuo to obtain crude material. The crude product was purified by flash chromatography using 40% ethyl acetate in hexane as eluent to provide 5-nitro-3-(1-phenylcyclopropyl)quinazoline-4(3H)-one as a beige solid (0.37 g, 58%). LCMS (ES) m / z calculated for C17H13N3O3, 307.1; found 308.1 [M+H] +. Step 3: synthesis of 5-amino-3-(1 -phenylcyclopropyl)quinazoline-4(3 / - / )-one To a stirred solution of 5-nitro-3-(1-phenylcyclopropyl)quinazolin-4(3 / - / )-one (0.37 g, 1.2 mmol) in THF (5 ml), water (0.5 ml) and methanol (0.5 ml) Zn powder (172 mg, 3.6 mmol) and NH4CI (270 mg, 6.01 mmol) were added. The resulting reaction mixture was allowed to stir at room temperature for 3 h. Once the reaction was complete, the reaction mixture was quenched with ice water (15 ml) and extracted with ethyl acetate (25 x 2 ml). The organic phase was washed with brine solution (10 mL) and dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to give 5-amino-3-(1-phenylcyclopropyl)quinazoline-4(3 / - / )-one as a pale yellow solid (0.301 g, crude). LC-MS m / z calculated for C17H15N3O, 277.1; found 278.2 [M+H] +. Step 4:3,5-dichloro-4-hydroxy-AA(4-oxo-3-(1-phenylcyclopropyl)-3,4-dihydroquinazolin5-yl)benzamide To a stirred solution of 5-amino-3-(1-phenyl cyclopropyl) quinazolin-4(3H)-one (0.14 g, 0.505 mmol) in chlorobenzene was added 3,5-dichloro-4-hydroxybenzoic acid. (0.092 g, 0.505 mmol) and phosphorus trichloride (0.06 mi, 0.75 mmol) at 0 °C. The resulting reaction mixture was heated at 130 °C for 3 h. After completion of the reaction, the reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (2 x 25 mL). The organic phase was washed with water, brine solution, dried over anhydrous sodium sulfate and concentrated to obtain crude material. Which was further purified by preparative HPLC, pure fractions were collected and lyophilized to produce 3,5-dichloro-4-hydroxy-N-(4-oxo-3-(1 oonRHn / cznz / a / υιλι 101 phen¡lcycloprop¡l)-3,4-d¡hydroqu¡nazolín-5-¡l)benzamide as a beige solid (10 mg, 4%). LCMS (ES) m / zcale, for C24H17CI2N3O3, 465.06; found, 466.1.* 1 * * *H NMR (400 MHz, DMSO-cfc) δ 12.88 (s, 1H), 11.15 (s, 1H), 8.69-8.62 (m, 2H), 7.86-7.82 (m, 3H ), 7.43-7.41 (d, J = 8 Hz, 1H), 7.32-6.92 (m, J = 8.4 Hz, 5H), 1.68-1.61 (m, 4H). Example 21: Synthesis of 3,5-dichloro-N-(3-(1-(2-fluorophenyl)cyclopropyl)-4-oxo-3,4dihydroquinazolin-5-yl)-4-hydroxybenzamide or The title compound was synthesized as described in example 20. LCMS (ES) m / z cale, for C24H16CI2FN3O3 483.06; found, 484.0 (M+H);1H NMR (400 MHz, DMSO c / 6): δ 12.91 (s, 1H), 11.19 (br, 1H), 8.65-8.60 (m, 2H), 7.89 (s, 2H) ), 7.89 - 7.71 (m, 2H), 7.38 - 7.32 (m,2H), 7.21 -7.14 (m,2H), 1.69-1.67 (m,2H), 1.56-1.54 (m, 2H). Example 22: 4,6-dichloro-A / -{3-[(3-fluorophenyl)methyl]-4-oxo-3,4-dihydroquinazolin-5yl}-5-hydroxypyridine-2-carboxamide H.O. TFA. .-h WC Step 1 SOCI-MeOH. !>:: c 3h Step 2 liCH THF H.O. RT 2h Step 3 PCI Chlorobenzene <u c ihStep 4 I ¡Cl. pTSA ΝΜΓ 2C0:C 2h Step 5 Step 1:1-2-bromo-6-carboxy-3-methoxypyridine oxide To a stirred solution of 6-bromo-5-methoxypyridine-2-carboxylic acid (1.20 g, 5.17 mmol) in TFA (20 ml) hydrogen peroxide (20 ml, 50%) was added and stirred at 90 °C for 36 h under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to provide 2-bromo-6-carboxy-3-methoxypyridine 1-oxide as an off-white solid (1.2 g). LCMS (ES) m / z cale, for C7H6BrNO4, 246.95; found, 248.0 (M+H). Step 2:methyl 4,6-dichloro-5-methoxypyridine-2-carboxylate A mixture of 2-bromo-6-carboxy-3-methoxypíhdine 1-oxide (0.8 g, 3.23 mmol) and thionyl chloride (5 ml) was stirred at 80°C for 2 h under a nitrogen atmosphere. . After completion of the reaction, excess thionyl chloride was removed in vacuo to give a residue which was quenched with methanol with stirring for 1 hour. The methanol was removed under pressure 102 reduced to give a crude residue which was dissolved in 20% IPA in DCM (10 ml). The organic layer was washed with sodium bicarbonate solution (5 ml), brine solution, dried over anhydrous sodium sulfate, filtered and concentrated. The crude material was purified by flash column chromatography using 15% ethyl acetate in hexane as eluent to provide methyl 4,6-dichloro-5-methoxypyridine-2-carboxylate as an off-white solid. (0.35g). LCMS (ES) m / z cale, for C8H7CI2NO3, 234.98; found, 236.0 (M+1). 1H NMR (400 MHz, DMSO-Ó6) δ 8.19 (s, 1H), 3.97 (s, 3H), 3.89 (s, 3H). Step 3: 4,6-Dichloro-5-methoxypyridine-2-carboxylic acid To a stirred solution of methyl 4,6-dichloro-5-methoxypyridin-2-carboxylate (0.3 g, 1.27 mmol) in THF: water (1:1) (6 mi) Lithium hydroxide (0.152 g, 6.35 mmol) was added and then stirred at room temperature for 2 h. Once the reaction was complete, the reaction mixture was evaporated in vacuo to obtain a residue that was diluted with water (10 ml) and acidified with 1N HCl (pH~6). The solid obtained was filtered and washed with water, dried to provide 4,6-dichloro-5-methoxy¡pyridín-2-carboxylic acid as an off-white solid (0.25 g). LCMS (ES) m / zcale, for C7H5CI2NO3, 220.96; found, 222.0 (M+H). Step 4: 4,6-dichloro-N-{3-[(3-fluorophenyl)methyl]-4-oxo-3,4-dihydroquinazolin-5-yl}-5methoxypyridine-2-carboxamide To a stirred solution of 4,6-dichloro-5-methoxypiñdin-2-carboxylic acid (0.05 g, 0.225 mmol), 5-amino-3-[(3-fluorophen¡l)met ¡l]-3,4-d¡hydroquinazolin-4-one (0.06 g, 0.225 mmol) in chlorobenzene (1 ml) phosphorus trichloride (0.031 mg, 0.225 mmol) was added at room temperature and then heat at 130 °C for 3 hours. After completion of the reaction, the reaction mixture was poured into ice water (10 mL) and extracted with 20% IPA in DCM (2x10 mL). The combined organic layer was washed with brine solution, dried over anhydrous sodium sulfate, filtered and concentrated to obtain 4,6-dichloro-N-{3-[(3-fluorophenyl)methyl]-4- oxo-3,4d¡hydroqu¡nazol¡n-5-yl}-5-methoxy¡pyr¡din-2-carboxamide as an off-white solid (0.07 g). LCMS (ES) m / z cale, for C22H15CI2FN4O3, 472.05; found, 473.0 (M+H). Step 5: 4,6-dichloro-N-{3-[(3-fluorophen¡l)methyl]-4-oxo-3,4-d¡hydroqu¡nazol¡n-5-yl}- 5hydroxypyridine-2-carboxamide To a stirred solution of 4,6-dichloro-A / -{3-[(3-fluorophenyl)methyl]-4-oxo-3,4dihydroquinazolin-5-¡l}-5- methoxypyridin-2-carboxamide (0.06 g, 0.127 mmol) in 1-methylpyrrolidin2-one (1.00 mL) p-toluene sulfonic acid (0.109 g, 0.634 mmol) and lithium chloride were added (26.9 mg, 0.634 mmol). The resulting reaction mixture was heated at 200 °C for 2 h. After completion of the reaction, the reaction mixture was quenched with water (5 ml) and extracted with 20% IPA / DCM (10 ml). The organic layer was washed with brine solution, dried over sodium sulfate, filtered and concentrated. The crude material was purified by Prep-HPLC to produce 4,6-dichloro-N-{3-[(3-fluorophenyl)methyl]-4-oxo-3,4-dihydroquinazolín-5-¡l}-5 -hydroxypyridine oonRhn / cznz / a / υιλι 103 2-carboxamide (13.2 mg) as an off-white solid. LCMS (ES) m / z cale, for C21H13CI2FN4O3, 458.03; found, 459.1 (M+H), 1H NMR (400 MHz, DMSO-C6) δ 13.52 (s, 1H), 8.84 (d, J= 8 Hz, 1H), 8.60 (s, 1H), 8.11 (s, 1H), 7.87 (m, 1H), 7.45 (m, 2H), 7.31 (d, J=8Hz, 1H), 7.26 (d, J=8Hz, 1H), 7.17 (m, 1H), 5.26 (s, 2H). Example 23: Synthesis of 4,6-dichloro-5-hydroxy-N-(4-oxo-3-{[2(trifluoromethoxy)phenyl]methyl}-3,4-dihydroquinazolin-5-yl)pyridine-2-carboxamide The title compound was synthesized as described in example 22. LCMS (ES) - m / z cale, for C22H13CI2F3N4O4, 524.03; found, 525.0 (M+H), 99.84% at 254 nm. 1H NMR (400 MHz, DMSO-Ó6) δ 13.5 (s, 1H), 8.84 (d, J= 8 Hz, 1H), 8.55 (s, 1H), 8.12 (s, 1H), 7.88-7.84 (m, 1H), 7.49 (m, 3H), 7.37 (m, 2H), 5.33 (s, 2H). Example 24: Synthesis of 4-(3,5-dichloro-4-hydroxybenzamido)-N-(2fluorobenzyl)thiazole-5-carboxamide Step 1 Step 2 Step 3 Step 1: Synthesis of methyl 4-(3,5-dichloro-4-hydroxybenzamide)thiazole-5-carboxylate To a suspension of methyl 4-amino-1,3-thiazol-5-carboxylate (600 mg, 3.79 mmol) and 3,5-dichloro-4-hydroxybenzoic acid (785 mg, 3.79 mmol) in Acetonitrile (12.0 mL) was added Phosphorus trichloride (332 pL, 3.79 mmol) dropwise under a nitrogen atmosphere. The reaction mass was heated at 100 °C for 3 h. After completion of the reaction, the reaction mass was cooled to room temperature and ice water (20 ml) was added, filtered and dried under vacuum to provide 4-(3,5-dichloro-4-hydroxy¡benzamido). Methyl thiazole-5-carboxylate (800 mg, 60%) as yellow solid, LCMS (ES) m / zcalculated, for C12H8CI2N2O4S, 345.96; found, 347 (M+H). Step 2: synthesis of 4-(3,5-dichloro-4-hydroxybenzamido)thiazole-5-carboxylic acid To a stirred solution of methyl 4-(3,5-dichloro-4-hydroxybenzamide)-1,3-thiazole-5-carboxylate (400 mg, 1.15 mmol) in THF: MeOH: H2O (6:2: 2) Lithium hydroxide (96.7 mg, 2.30 mmol) was added. The reaction mixture was stirred for 20 hours at room temperature. After the reaction was completed, the reaction mass was concentrated to obtain the crude product. He 104 crude material was diluted with water (10 ml_) and acidified with 1 M HCl (10 mL) to pH 2-3 and extracted with EtOAc (2X10 mL) and washed with water (2X15 mL) and brine solution, The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to provide 4-(3,5-dichloro-4-hydroxybenzamide)-1,3-thiazole-5-carboxylic acid (300 mg, 0.901 mmol) as an off-white solid, calculated LCMS (ES)m / z, for C11H6CI2N2O4S, 333.94; found, 334.9(M+H). Step 3: Synthesis of 4-(3,5-dichloro-4-hydroxybenzamido)-N-(2-fluorobenzyl)thiazole-5carboxamide A stirred solution of 4-(3,5-dichloro-4-hydroxy¡benzamide)-1,3-thiazole-5carboxylic acid (140 mg, 0.420 mmol) in thionyl chloride (3.00 mL, 41.4 mmol) was heated at 95 °C for 2 h. Excess thionyl chloride was removed by distillation in a rotary evaporator. The residue obtained was dissolved in DMF (1 mL) and added to a stirred solution of (2fluorophenyl)methanamine (47.8 pL, 0.420 mmol), DMAP (103 mg, 0.840 mmol), DiPEA (0.734 ml, 4.20 mmol) in DMF (2 mL) and heated at 85 °C for 3 h. After the reaction was completed, the reaction mixture was cooled to room temperature and quenched with water (10 mL) and extracted with ethyl acetate (10 mL X 2) and washed with brine (10 mL) and the mixture was collected. organic layer, dried over sodium sulfate and filtered and concentrated in vacuo to give a crude product that was purified by preparative reverse phase HPLC. The pure fractions were collected and concentrated to produce pure 4-(3,5-dichloro-4-hydroxybenzamide)N-(2-fluorobenzyl)thiazole-5-carboxamide (30.0 mg, 16%) an off-white solid. LCMS (ES) m / z cale. C18H12CI2FN3O3S, 439.0; found, 440.0(M+1).1H NMR (400 MHz, DMSO 56) 5:11.02 (br, 1H), 10.94 (s, 1H), 9.12 (s, 1H), 8.71 (br, 1H), 7.93 ( s, 2 H), 7.34 (t, J=7.8Hz, 1H), 7.26-7.24 (m, 1H), 7.12-7.03 (m, 2H), 4.41 (d, J= 4.8 Hz, 2H). oonRhn / cznz / a / υιλι The following compounds were synthesized as described in Example 24. E¡· Spectral data 25 LCMS(ES) m / z, cale, for C20H14CI2F3N3O3S, 503.31; found 504 (M+H): 1H NMR (400 MHz, DMSO-dB) δ: 10.97(s, 1H), 9.11 (s, 1H), 8.43-8.40(m, 1H), 7.95 (s, 2H), 7.50 (d, J=8.4Hz, 2H), 7.58-7.54(m, 1H), 7.61 (d, J=8.4Hz, 1H), 7.40-7.37 (m, 1H), 3,473.42 (m, 2H ), 2.94(t, J=7.6Hz, 2H). 26 LCMS (ES) m / z cale, for C19H12CI2F3N3O3S, 488.9; found, 489.9 (M+1). 1H NMR (400 MHz, DMSO Ó6) 5:11.03 (br, 1H), 10.92 (s, 1 H), 9.13 (s, 1H), 8.77-8.74 (m, 1H), 7.93 (s, 2 H), 7.66 (d, J=7.2 Hz, 1 H), 7.56-7.51 (m, 2 H), 7.45-7.43 (m, 1 H), 4.54 (s, 2 H). 27 LCMS (ES) m / zcale, for C19H12CI2F3N3O4S, 504.99; found, 505.9 (M+H), 1H NMR (400 MHz, DMSO-cfc) δ 10.97 (s, 2H), 9.15 (s, 1H), 8.72 (t, J= 5.6 Hz, 1H), 7.96 (s, 2H), 7.46 (d, J= 7.6 Hz, 1H), 7.40-7.36 (m, 1H), 7.32-7.27 (m, 2H), 4.47 (d, J= 6.0 Hz, 2H). 28 LCMS (ES) m / zcale, for C18H11CI2F2N3O3S, 456.99; found, 457.9 (M+H), 1H NMR (400 MHz, DMSO-oG) δ ; 11.0 (s, 1H), 10.93 (s, 1H), 9.14 (s, 1H), 8.69 (t, J=7.6 Hz, 1H), 7.94 (s, 2H), 7.44 - 7.38 (m, 1H), 7.15 -6.98 (m, 2H), 4.39 (d, J = 5.6 Hz, 2H). 29 LCMS (ES) m / z cale, for C20H14CI2FN3O3S, 466.31; found 466.0 [M+H]+. 105 AND. 1HNMR spectral data (400 MHz, DMSO-d6): δ 11.03 (s, 1 H), 10.94 (s, 1 H), 9.11 (s, 1 H), 8.94 (s, 1 H), 7.99 (s, 2 H), 7.21 -7.25 (m, 2 H), 7.06 (t, J= 8.8 Hz, 2 H), 1.14 (d, J=3.2 Hz, 4 H). 30 LCMS (ES) m / z cale, for C18H17CI2F2N3O3S, 464.31; found, 466.0 (M+H), 1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 10.96 (s, 1H), 9.12 (s, 1H), 8.28-8.25 (m, 1H), 7.99 (s, 2H), 3.10-3.07 (m, 2H), 1.93-1.91 (m, 2H), 1.72-1.57 (m, 5H) and 1.171.08 (m, 2H). Example 31: Synthesis of 5-(3,5-dichloro-4-hydroxybenzamido)-N-(2-fluorobenzyl)-3methylisothiazole-4-carboxamide Me-,ΛΙ C'Men . ·%. ' toluene) Toluene1pindma 100 O. 1ti O’-RT Ίτ Step 1 ...Step2o j ] BBlj. DCM ·: f p ... .1. / AQ - Ίί; Step 3 Step 1: Synthesis of 5-amino-N-(2-fluorobenzyl)-3-methylisothiazole-4-carboxamide To a stirred solution of methyl 5-amino-3-methyl-1,2-thiazole-4-carboxylate (100 mg, 581 pmol) and 1-(2-fluorophenyl)methanamine (80.0 μΙ_, 697 pmol) in toluene (1.00 ml) cooled to 0sC, trimethylalumane (871 μΙ, 1.74 mmol) was added dropwise. The resulting reaction mixture was heated at 100 °C for 1 h. Once the reaction was complete, the reaction mixture was quenched with cold water (5 mL) and extracted into EtOAc (5 mL x 2). The combined organic layer was washed with brine (10 mL), dried over sodium sulfate, and evaporated under reduced pressure to give 5-amino-N-(2-fluorobenzyl)-3-methylsot. Azole-4-carboxamide as a yellow solid (130 mg, 84%). The crude compound was taken to the next step without further purification. LCMS (ES) m / z cale. For C12H12FN3OS, 265.31; found, 266 (M+H)+. Step 2: Synthesis of 5-(3,5-dichloro-4-methoxybenzamido)-N-(2-fluorobenzyl)-3methylisothiazole-4-carboxamide To a stirred solution of 3,5-dichloro-4-methoxybenzoic acid (200 mg, 905 μητοΙ) in pyridine (2.50 mL) was added phosphoryl chloride (127 pL, 1.36 mmol) at 0 °C and allowed to cool. stirring for 10 min. To this was added 5-amlno-N-[(2-fluorophen¡l)methyl]-3-methyl-1,2-thiazole-4carboxamide (240 mg, 905 μητοΙ) and then stirred at room temperature for 1 hour. Once the reaction was completed, the reaction mass was quenched with cold water (10 ml). The precipitated solid was filtered, washed with hexane (10 mL) and dried to give 5-(3,5-dichloro-4methoxybenzamido)-N-[(2-fluorophenyl)methyl]-3- methyl-1,2-thiazole-4-carboxamide (200 mg, 48%) 106 as a brown solid which was taken as such for the next step without further purification. LCMS (ES) m / z cale. For C20H16CI2FN3O3S, 468.32; found, 468 (M+H)+. Step 3: Synthesis of 5-(3,5-dichloro-4-hydroxybenzamido)-N-(2-fluorobenzyl)-3methylisothiazole-4-carboxamide To a stirred solution of 5-(3,5-dichloro-4-methoxybenzamide)-N-[(2-fluorophenyl)methyl]-3methyl-1,2-thiazole-4-carboxamide (200 mg , 427 pmol) in DCM (0.1 ml) cooled to 0 °C, tribromoborane (405 μΙ, 4.27 mmol) was added dropwise and allowed to stir at room temperature for 16 h. Once the reaction was complete, the reaction mixture was quenched with ice water and extracted into EtOAc (10 ml x 2). The combined organic layer was washed with brine (10 mL), dried over sodium sulfate, and evaporated under reduced pressure to yield a crude compound that was purified by flash chromatography. The column-purified compound was purified by reverse-phase preparative HPLC to provide 5-(3,5dichloro-4-hydroxy¡benzamide)-N-[(2-fluorophen¡l)methyl]-3-met¡ Pure l-1,2-thiazole-4-carboxamide (40.0 mg, 20.62%). LCMS (ES) m / zcale, for C19H14CI2FN3O3S 454.30; found, 454 (M+H)+. 1H NMR (400 MHz, DMSO d6) δ 11.95 (br, 1H), 11.5 (br, 1H), 8.63 (br, 1H), 7.93 (s, 2H), 7.45 (t, J = 14.8 Hz, 1H), 7.34 - 7.31 (m, 1H), 7.30 - 7.28 (m, 2H), 4.57 (d, J = 5.6 Hz, 2H), 2.48 (br, 3H). Example 32: Synthesis of 5-(3,5-dichloro-4-hydroxybenzamido)-N-(2(trifluoromethoxy)benzyl)thiazole-4-carboxamide J-L ..oClI <: H-rfc ' ’(HO. '· , ',H Step 1 Step 2 a ,l oonRhn / cznz / a / υιλι Step 3 step4 c Step 1: Synthesis of methyl 5-(3,5-dichloro-4-methoxybenzamido)thiazole-4 carboxylate To a stirred solution of methyl 5-amino-1,3-thiazol-4-carboxylate (0.15 g, 0.99 mmol) in dichloromethane (4.00 ml) was added N,N-dimethylpyridine-4-amine. (152 mg, 1.24 mmol) and tnetylamine (1.73 ml, 12.4 mmol) at room temperature and then stirred for 10 minutes. To this was added 3,5-dichloro-4-methoxybenzoyl chloride (298 mg, 1.24 mmol) in dichloromethane (4.00 ml) slowly at 0 °C under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for an additional 1 hour. Once the reaction was complete, the reaction mixture was quenched with water (30 ml) and extracted with DCM (2 x 100 ml). Organic extracts The combined 107 were washed with brine solution (30 mL) and dried over anhydrous sodium sulfate, filtered and dried under vacuum to obtain crude material. The crude material was purified by flash column chromatography to provide methyl5-(3,5-dichloro-4-methoxybenzamide)thiazole-4 carboxylate (150 mg, 33.37%) as an off-white solid. LCMS (ES) m / z cale. For C13H10CI2N2O4S, 359.9; found, 361.0 (M+H). Step 2: Synthesis of 5-(3,5-dichloro-4-hydroxybenzamido)thiazole-4-carboxylic acid To a stirred suspended solution of methyl-5-(3,5-dichloro-4methoxybenzamido)-1,3-thiazol-4 carboxylate (126 mg, 0.349 mmol) in dichloromethane (0.5 mL) was added borane bromide (0.596 mL). , 3.49 mmol) at 0 °C. The resulting reaction mixture was stirred at room temperature for 12 hours. Once the reaction was completed, the reaction mixture was quenched with ice water (20 mL) and extracted with ethyl acetate (2 x 25 mL), the combined organic extracts were washed with brine solution (20 mL) and dried. over anhydrous sodium sulfate, filtered and concentrated under vacuum to give crude 5-(3,5-dichloro-4-hydroxybenzamide)thiazole-4-carboxylic acid (93.0 mg, 80%). , crude) as a whitish solid. LCMS (ES) m / z cale, for C11H6CI2N2O4S, 333.91; found, 335.0 (M+H). Step 3: Synthesis of 5-(3,5-dichloro-4-hydroxyphenyl)-7 / 7-thiazolo[5,4-cf][1,3]oxazin-7-one To a stirred solution of 5-(3,5-dichloro-4-hydroxy¡benzamide)-1,3-thiazol-4carboxylic acid (93.0 mg, 0.279 mmol) in 1,2-dichloroethane (5 ml) was added thionyl chloride. (0.202 mL, 2.79 mmol) and then heated at 70 °C for 2 hours. After completion of the reaction, the reaction mixture was concentrated under vacuum to produce crude 5-(3,5-dichloro-4-hydroxytenyl)-7Hthiazolo[5,4-d][1,3]oxazin-7-one ( 78.0 mg, 88.67%, crude material) as a solid brown substance. LCMS (ES) m / z cale. For C11H4CI2N2O3S, 313.93; found, 312.9 (M-H). Step 4: Synthesis of 5-(3,5-dichloro-4-hydroxybenzamido)-N-(2(trifluoromethoxy)benzyl)thiazole-4-carboxamide To a stirred solution of 5-(3,5-dichloro-4-hydroxyphenyl)-7H-[1,3]thiazolo[5,4-d][1,3]oxazin7-one (93.0 mg, 0.295 mmol) in Ν,Ν-dimethylformamide (4.00 mL), DiPEA (0.154 mL, 0.885 mmol) and 1-[2-(trifluoromethox¡)phen¡l]methanamine (67.7 mg, 0.354 mmol) were added at room temperature. The resulting reaction mixture was heated at 90 °C for 2 hours. Once the reaction was complete, the reaction mixture was quenched with ice water (30 ml) and extracted with ethyl acetate (2 x 50 ml). The combined organic extracts were washed with brine solution (30 ml) and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by flash column chromatography to provide 5-(3,5-dichloro-4-hydroxy¡benzamide)-N-(2-(trifluoromethoxy)benzyl)thi azole-4carboxamide (23.0 mg, 15.39%) as an off-white solid. LCMS (ES) m / z cale. For oonRHn / cznz / a / υιλι 108 C19H12CI2F3N3O4S, 504.99; found, 503.9 (M-H). HNMR (400 MHz, DMSO-P6) δ 12.35 (s, 1 H), 8.31 (s, 1 H), 7.94 (s, 2H), 7.68 (br, 1 H), 7.50 (d, J= 7.2 Hz, 1H), 7.37-7.25 (m, 3H), 6.30 (s, 1H), 4.77 (d, J= 6 Hz, 2H). The following compounds have been synthesized using a procedure as described in Examples 1-4, 20-24 and 31-32. E¡· Spectral data 33 LCMS (ES) m / z cale, for C18H12CI2FN3O3S, 439.0; found, 440.0 (M+H). 1HNMR (400 MHz, DMSO-c / 6) δ 12.38 (s, 1H), 11.41 (s, 1H), 9.21 (s, 1H), 8.73 (s, 1H), 7.84 (s, 2H), 7.38- 7.31 (m, 2H), 7.21-7.17 (m, 2H), 4.60 (d, J= 7.6 Hz, 2H). 34 LCMS (ES) m / z cale, for C18H12CI2FN3O3S, 439.0; found, 439.0 (M-H). HNMR (400 MHz, DMSO-d6) δ 12.40 (s, 1H), 11.30 (s, 1H), 9.32 (t, J = 6.2 Hz, 1H), 8.73 (s, 1H), 7.84 (s, 2H) , 7.41-7.35 (m, 1H), 7.21-7.15 (m, 2H), 7.10-7.05 (m, 1H), 4.55 (d, J=6.4 Hz, 2H). 35 LCMS (ES) m / zcale, for C21H18CI2N2O4S, 464.0; found, 464.9 (M+H). Ή NMR (400 MHz, DMSO-de) δ 12.09 (s, 1 H), 11.10 (s, 1 H), 8.40 (s, 1H), 7.99 (d, J=5.2 Hz, 1H), 7.75 (m, 3H), 7.11-7.18 (m, 2H), 6.93 (d, J= 8Hz, 1H), 6.83 (t, J =7 Hz, 1H), 3.77 (s, 3H), 3.45 (d, J= 5.2 Hz , 2H), 2.81 (m, 2H). 36 LCMS (ES) m / zcale, for C24H19CI2N3O4, 483.08; found, 482.1 (M-H). NMR (400 MHz, DMSO-06) δ 13.01 (s, 1H), 11.20 (bs, 1H), 8.68 (d, J=7.6 Hz, 1H), 7.98 (s, 1H), 7.88 (s, 2H), 7.78 (t, J=16.8 Hz, 1H), 7.31 (d, J=8 Hz, 1H), 7.17 (t, J=14.8 Hz, 1H), 7.09 (d, J=6.8 Hz, 1H), 6.88 ( d, J=8 Hz, 1H), 6.81 (t, J=14.4 Hz, 1H), 4.24 (t, J=12.8 Hz, 2H), 3.55 (s, 3H), 3.02 (t, J=12.4 Hz, 2H). 37 LCMS (ES) m / zcale, for C20H12CI3F3N2O4S, 537.9; found, 538.8 (M+H). Ή NMR (400 MHz, DMSO-ofe): δ 13.09 (s, 1H), 11.31 (bs, 1H), 9.04 (t, J= 6.0 Hz, 1H), 7.81 (s, 2H), 7.65 (s, 1H ), 7.49-7.38 (m, 4H), 4.60 (d, J = 5.6 Hz, 2H). 38 LCMS (ES) m / z cale, for C21H14CI3F3N2O4S, 551.97; found, 553.0. 1H NMR (400 MHz, DMSO-06): δ 13.19 (s, 1H), 11.33 (s, 1H), 8.66 (t, J = 5.2 Hz, 1H), 7.80 (s, 2H), 7.54 (s, 1H ), 7.46 (t, J= 9.6 Hz, 1H), 7.39-7.32 (m, 3H), 3.54 (d, J= 6.8 Hz, 2H), 2.96 (t, J=7.2Hz,2H). 39 LCMS (ES) m / zcale, for C18H11CI2N5O3S, 447.0; found, 448.0. 1H NMR (400 MHz, DMSO-Ó6) δ 12.77 (s, 1H), 11.25 (bs, 1H), 9.62 (s, 1 H), 8.72 (d, .7=8.4 Hz, 1 H), 8.67 (s , 1 H), 7.88-7.92 (m, 3 H), 7.47 (d, J= 7.6 Hz, 1H), 5.79 (s, 2 H). 40 LCMS (ES): m / z cale, for C22H13CI2F3N4O3, 508.03; found, 509.0 (M+H). 1H NMR (400 MHz, DMSO-cfe): δ 13.35 (bs, 1H), 8.83 (d, J=8.0 Hz, 1H), 8.65 (s, 1H), 7.98 (bs, 1H), 7.89 (s, 1H ), 7.84-7.79 (m, 1H), 7.73-7.68 (m, 2H), 7.63-7.59 (m, 1H), 7.38 (d, J= 8.0 Hz, 1 H), 5.32 (s, 2H). 41 LCMS (ES): m / zcale, for C22H15CI2FN4O3, 472.05; found, 471.0 (M-H). 1H NMR (400 MHz, DMSO-cfe): δ 13.60 (s, 1H), 8.85 (d, J= 7.6 Hz, 1H), 8.45 (s, 1H), 8.14 (s, 1H), 7.87-7.83 (m , 1H), 7.46-7.40 (m, 2H), 7.36-7.34 (m, 1H), 7.27 (d, J = 7.6 Hz, 1H), 7.20-7.14 (m, 1H), 6.17 (q, J = 7.2 Hz, 1H), 1.90 (d, J = 7.2 Hz, 3H). 42 LCMS (ES): m / zcale, for C21H13CI2FN4O3, 458.03; found, 459.0 (M+H), 1H NMR (400 MHz, DMSO-ofe): δ 13.56 (s, 1H), 8.84 (d, J=7.6 Hz, 1H), 8.61 (s, 1H), 8.13 (s , 1H), 7.87-7.83 (m, 1H), 7.51-7.48 (m, 2H), 7.42 (d, J = 7.6 Hz, 1H), 7.23-7.18 (m, 2H), 5.24 (s, 2H). 43 LCMS (ES): m / z cale, for C22H13CI2F3N4O3, 508.03; found, 509.0 (M+H). 1H NMR (400 MHz, DMSO-cfe) δ 13.42 (s, 1H), 8.83 (d, J= 8.0 Hz, 1H), 8.53 (s, 1H), 8.08 (s, 1H), 7.89-7.85 (m, 1H), 7.81 (d, J= 8.0 Hz, 1H), 7.61-7.57 (m, 1H), 7.53-7.49 (m, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 5.43 (s, 2H). 44 LCMS (ES): m / z cale, for C21H13CI2FN4O3, 458.03; found 459.0 (M+H). 1HNMR (400 MHz, DMSO-d6): δ 13.46 (s, 1H), 8.81 (d, J = 8.0 Hz, 1H), 8.54 (s, 1H), 8.06 (s, 1H), 7.85-7.81 (m , 1H), 7.41 -7.34 (m, 3H), 7.23-7.17 (m, 2H), 5.27 (s, 2H). 109 AND. Spectral data 45 LCMS (ES): m / z cale, for C27H25CI2N5O3 537.13; found, 538.1 (M+H). 1H NMR (400 MHz, DMSO-cfe): δ 12.58 (s,1H), 8.73 (d, J = 7.6, Hz, 1H), 8.52 (s, 1H), 7.74-7.70 (m, 1H), 7.64 ( s, 2H), 7.28-7.23 (m, 3H), 6.89 (d, J = 8.8 Hz, 2H), 5.12 (s, 2H), 3.36 (s, 3H hidden under the humidity peak of DMSO-C6), 3.09-3.06 (m, 2H), 2.48 (m, 2H hidden under the solvent peak of DMSO-c / 6), 2.43-2.40 (m, 2H), 2.17 (s, 2H). 47 LCMS (ES): m / z cale, for C23H16CI2FN3O3, 471.05; found, 472 (M-1). 1H NMR (400 MHz, DMSO): δ 12.99 (s, 1H), 11.17 (s, 1H), 8.72 (d, J= 8.0 Hz, 1H), 8.46 (s, 1H), 7.93 (s, 2H ), 7.86 (t, J= 8.4 Hz, 1H), 7.46 - 7.41 (m, 2H), 7.34 (d, J= 10.4 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.19-7.15 (m, 1H), 6.22- 6.20 (m, 1H), 1.88 (d, J = 4.0 Hz, 3H). 48 LCMS (ES) m / z cale, for C23H14CI2N4O3, 464.04; found, 465.0 (M+H). 1H NMR (400 MHz, DMSO d6): 12.82 (s, 1H), 11.09 (bs, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.56 (s, 1 H), 7.86-7.77 (m, 4H), 7.73-7.67 (m, 2H), 7.52 (t, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H),5.25 (s, 2H). 49 LCMS (ES) m / z cale, for C22H13CI2F3N4O4; 524.03; found, 525.0 (M+H). 1H NMR (400 MHz, DMSO-d6); δ 13.54 (s, 1H), 8.84-8.82 (m, 1H), 8.64 (s, 1H), 8.12 (s, 1H), 7.85 (t, J=8.0 Hz, 1H), 7.6-7.4 (m, 4H ), 7.33-7.32 (m, 1H), 5.29 (s, 2H). 50 LCMS (ES) m / z cale, for C22H13CI2F3N4O4, 524.03; found 525.0 (M+H1H NMR (400 MHz, DMSO-d6): δ 13.46 (s, 1H), 8.81 (d, J= 8.4 Hz, 2H), 8.59 (s, 2H), 8.07 (s, 2H), 7.82 (t, J = 7.8 Hz, 1H), 7.52 (d, J = 8 Hz, 1H), 7.40-7.34 (m, 2H), 5.26 (s, 2H). for C23H17CI2N3O5S; found, 519.9 (M+H), 1H NMR (400 MHz, DMSO-d6); ), 8.60 (s, 1H), 7.94-7.97 (m, 1H), 7.83 (t, J = 8.0 Hz, 1H), 7.75 (s, 2H), 7.50-7.60 (m, 2H), 7.42 (d , J= 7.6 Hz, 1 H), 7.13 (d, J= 7.6 Hz, 1H), 5.61 (s, 2H), 3.44 (s, 3H). ; found, 486.1 (M+H), 99.44% at 245 nm NMR (400 MHz, DMSO-cfe); , 1H), 7.83-7.80 (m, 3H), 7.78-7.70 (m, 1H), 7.38 (d, J= 8.0 Hz, 1H), 6.22 (d, J= 2.4 Hz, 1H), 5.246 (s, 2H), 1.49 (s, 9H). 53 LCMS (ES) m / zcale, for C23H14CI2N4O3, 464.0; found, 465.0 (M+H). ), 11.14 (bs, 1H), 8.70 (d, J= 8.0, 1H), 8.64 (s, 1H), 7.92-7.87 (m, 4H), 7.69-7.65 (m, 1 H), 7.54-7.50 ( m, 1H), 7.47 (d, J = 8.0 Hz, 1 H), 7.40 (d, J=7.6 Hz, 1H), 5.46 (s, 2H). 54 LCMS (ES) m / zcale.: C24H18CI2F2N4O3, 504.06; found, 505.0 (M+H). 1H NMR (400 MHz, DMSO-c / 6); δ 10.71 (s, 1H), 8.58 (s, 1H), 7.98 (t, J= 8.0 Hz, 1H), 7.52 (d, J= 8.0 Hz, 1H), 7.44-7.37 (m, 4H), 7.30 ( t, J= 8.0 Hz, 4H), 7.09, 6.97 (2s, 1H), 5.28 (s, 2H), 3.3 (s, 3H) in (solvent region). 56 LCMS (ES) m / z cale, for C20H15CI2N5O3, 443.06; found, 444.1 (M+H). 1H NMR (400 MHz, DMSO-d6); δ 12.96 (s, 1H), 11.17 (s, 1H), 8.69 (d, J= 7.6 Hz, 1H), 8.5 (s, 1H), 7.89 (s, 1H), 7.86 (m, 1H), 7.62 (d, 1H), 7.41 (d, J= 7.6 Hz, 1H), 6.24 (d, J= 2.4 Hz, 2H), 5.2 (s, 2H), 3.74 (s, 3H). 57 LCMS (ES) m / z cale, for C21H21CI2N3O3; 434.32 found, 434.1 (M+H). 1H NMR (400 MHz, DMSO-d6); δ 13.12 (s, 1H), 11.15 (bs, 1H), 8.68 (d, J = 8 Hz, 1 H), 8.51 (s, 1H), 7.94 (s, 2H), 7.84 (t, J = 8 Hz , 1 H), 7.41 (d, J = 8 Hz, 1 H), 4.08-4.04 (m, 2H), 1.66-1.62 (m, 2H) and 1.01 -0.97 (m, 9H). 58 LCMS (ES)m / zcalc. for C24H19CI2N3O5, 499.07; found, 498.1 (M-1). 1H NMR (400 MHz, DMSO-C6); δ 12.97 (bs,1H), 11.15 (bs, 1H), 8.71 (d, J= 8.4Hz, 1H), 8.61 (s, 1H), 7.91 (s, 2H), 7.85 (t, J= 8.4 Hz, 1H), 7.42-7.35 (m, 3H), 6.93 (d, J= 8.4 Hz, 2H), 5.20 (s, 2H), 4.80 (t, J= 5.6 Hz, 1H), 3.95 (t, J= 5.2 Hz, 2H), 3.70-3.66 (m, 2H). 59 LCMS (ES) m / z cale, for C23H17CI2N3O5S, 517.03; found, 516.0 (M-1). 1H NMR (400 MHz, DMSO-06); δ 12.84 (s, 1 H), 11.17 (bs, 1 H), 8.71 (d, J= 8.0 Hz, 1H), ΙΛ / tz / zuz ó / unauoo 110 AND. Spectral data 8.64 (s, 1H), 7.93-7.86 (m, 5H), 7.64 (d, J= 8.4, Hz, 2H), 7.45 (d, J=7.6 Hz, 1H), 5.40 (s, 2H), 3.19 (s, 3H). Purity 98.2% at 245 nm. 60 LCMS (ES) m / zcale, for C23H17CI2N3O5S, 517.03; found 518.0 (M+H), 98.02% at 254 nm. 1H NMR (400 MHz, DMSO-06); δ 12.88 (s, 1H), 11.17 (bs, 1H), 8.72-8.70 (m, 2H), 8.02 (s, 1H), 7.90-7.85 (m, 4H), 7.74 (d, J = 8.0 Hz, 1H ), 7.65 (t, J = 7.6 Hz, 1H), 7.45 (d, J = 8.0Hz, 1H), 5.39 (s, 2H), 3.21 (s, 3H). 61 LCMS (ES) - m / z cale, for C20H20CI2N4O3, 434.09; found, 435.1 (M+H). 1H NMR (400 MHz, DMSO-cfe) δ 13.72 (s, 1H), 8.83 (d, J= 8 Hz,1H), 8.47 (s, 1H), 8.13 (s, 1H), 7.84 (t, 1H) , 7.40(d, = 7.8 Hz, 1H), 4.07 - 4.02 (m, 2H), 1.66 -1.62 (m, 2H), 1.01 (s, 9H). 62 LCMS (ES) m / z cale, for C22H20CI2N6O3 486.10; found, 487.1 (M+H). 1H NMR (400 MHz, DMSO-c / 6) 513.5 (s, 1H), 8.8 (d, J = 8.4 Hz, 1H), 8.4 (s, 1H), 8.1 (s, 1H), 7.8 (t, J = 8.4 Hz, 1H), 7.7 (d, J = 2.4 Hz, 1H), 7.4 (d, J = 7.6 Hz, 1H), 6.2 (d, J = 2.4 Hz, 1 H), 5.2 (s, 2H) , 1.5 (s, 9H). 63 LCMS (ES) m / zcale, for C26H22CI2N4O5S, 572.07; found 573.0 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 13.01 (s, 1H), 11.17 (s, 1H), 8.70 (d, J= 8 Hz, 1H), 8.62 (s, 1H), 7.93 (s, 2H ), 7.85 (t, J = 8.2 Hz, 1H), 7.42 (d, J= 8 Hz, 1H), 7.34 (d, J = 8.8 Hz, 2H), 7.02 (d, J= 8.8 Hz, 2H), 5.18 (s, 2H), 3.76 (s, 4H), 3.08 (s, 4H). 64 LCMS (ES) m / z cale, for C24H16CI2F3N3O4; 537.05; found, 538.0 (M+H). 1H NMR (400 MHz, DMSO-06) δ: 12.8 (s, 1H), 11.13 (s, 1H), 8.67 (d, J= 7.6 Hz, 1H), 7.8-7.9 (m, 3H), 7.3-7.4 (m,4H),7.13 (d, J = 7.6 Hz, 1H), 5.46 (s, 2H), 3.35 (s, 3H). 65 LCMS (ES) m / z cale, for C23H14F2N4O3, 523.03; found 524.0 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 12.39 (bs, 1H), 10.54 (s, 1 H), 8.74 (d, J= 8 Hz, 1H), 8.52 (s, 1 H), 7.92 (t , J = 8 Hz, 1H), 7.52-7.43 (m, 3H), 7.40-7.32 (m, 2H), 7.27 (d, J=6.8 Hz,1H), 7.16 (d, J=8 Hz, 1H) , 5.26 (s, 2H). 66 LCMS (ES) m / zcale, for C22H13CI2N5O3, 465.04; found 466.0 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 13.40 (s, 1H), 8.77 (d, J= 7.6 Hz, 1H), 8.57 (s, 1H), 8.18 (s, 1 H), 8.06- 7.81 ( m, 2H), 7.66-7.62 (m, 1H), 7.50-7.37 (m, 3H), 5.38 (s, 2H). 67 LCMS (ES) m / z cale, for C23H15CI2N5O3, 479.06; found, 480.1 (M+H). 1H NMR (400 MHz, DMSO-ofe) δ 13.01 (s, 1H), 12.98 (s, 1H), 8.68 (d, J= 8.0 Hz, 1 H), 8.62 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.88 (s, 2H), 7.85-7.81 (m, 1 H), 7.50 (d, J = 8.4 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.37- 7.33 (m, 1H), 7.16-7.12 (m, 1H), 5.62 (s, 2H). 68 LCMS (ES): m / z cale, for C24H14CIF3N4O3, 498.07; found, 499.0 (M+H). 1H NMR (400 MHz, DMSO-ofc): δ 12.85 (s, 1H), 8.67-8.66 (m, 2H), 8.12 (d, J= 2.0 Hz, 1 H), 8.07 (d, J = 2.0 Hz, 1H), 7.87-7.83 (m, 2H), 7.68-7.66 (m, 2H), 7.60-7.56 (m, 1 H), 7.42 (d, J= 7.6 Hz, 1 H), 5.34 (s, 2H) . 69 LCMS (ES) m / zcale. C21H14CI2F3N3O4, 499.0; found, 498.0 (M-H). 1H NMR (400 MHz, DMSO-06) δ 13.0 (s, 1H), 11.17 (s, 1H), 9.82 (t, J = 8.0 Hz, 1H), 9.08-9.06 (m, 1H), 8.43-8.41 ( m, 1H), 7.92 (s, 2H), 7.72-7.69 (m, 1H), 7.44-7.37 (m, 4H), 4.64 (d, J=8.0 Hz, 2H). 70 LCMS (ES) m / z cale, for C24H13CI2F6N3O4, 591.08; found 591.9 (M+H). 1H NMR (400 MHz, DMSO-d6): 1H NMR (400 MHz, DMSO-d6): δ 12.15 (bs, 1H), 11.18 (s, 1H), 8.86 (d, J= 8 Hz, 1H), 8.03 (t, J = 8.4 Hz, 1H), 7.82 (s, 2H), 7.65 (d, J=7.6 Hz, 1H), 7.46-7.42 (m, 2H), 7.34-7.27 (m, 2H) ,5.45 ( d, J= 23.6 Hz, 2H). 71 LCMS (ES) m / zcale, for C20H22CI2N2O3, 408.1; found 409.2 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 12.39 (s, 1H), 11.07 (s, 1 H), 8.77 (d, J = 5.2 Hz, 1H), 8.48 (d, J = 8 Hz, 1 H ), 7.86 (s, 2H), 7.79 (d, J = 7.2 Hz, 1H), 7.54 (t, J = 7.2 Hz, 1H), 7.20 (t, J= 7.2 Hz, 1H), 3.40-3.41 (m , 2H), 1.51 - 1.47 (m, 2H), 0.948 (s, 9H). 72 LCMS (ES) m / zcale, for C22H13CI2N5O3, 484.05; found 485.1 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 13.61 (s, 1H), 8.77 (d, J= 7.6 Hz, 1H), 8.624 (d, J = 3.2 Hz, 1H), 8.10 (s, 1H), 7.83 - 7.81 (m, 2H), 7.39 - 7.37 (m, 2H), 7.21 (m, 2H), 1.68 (s, 2H), 1.56 (s, 2H). ΙΛ / tz / zuz ó / unauoo 111 AND. Spectral data 73 LCMS (ES) m / z cale, for C21H14CI2F3N3O4, 499.03; found 500.0 (M+H). 1H NMR (400 MHz, DMSO-c / β) δ 11.35 (s, 1H), 11.08 (s, 1H), 9.41 (t, J = 5.6Hz, 1 H), 9.33 (s, 1H), 8.52 (d , J = 4.8Hz, 1H), 7.73 (d, J = 4.8Hz, 2H), 7.53 (d, J = 7.2Hz, 1H), 7.437.39 (m, 1H), 7.35-7.30 (m, 3H) , 4.55 (d, J= 5.6Hz, 2H). 74 LCMS (ES) m / z C24H16CI2F3N3O4, cal 537.05; found 536.0 (M-H). 1HNMR (400 MHz, DMSO-de); δ 12.91 (s, 1H), 11.16 (s, 1H), 8.69 (d, J=8.0 Hz, 1H), 8.46 (s, 1H), 7.90-7.80 (m, 3H), 7.56-7.53(m, 2H) ), 7.40-7.35 (m, 3H), 6.22-6.18 (m, 1H), 1.871.86 (m, 3H). 75 LCMS (ES): m / z cale, for C22H13CIF4N4O3; 508.03 found 509.0, (M+H). 1H NMR (400 MHz, DMSO-d6):5 12.81 (s, 1H), 11.12(s, 1H), 8.70-8.68(m, 2H), 8.57(s, 1H), 8.28(d, J = 8 Hz , 1H), 7.91 -7.84(m, 3H), 7.59-7.56(m, 1H), 7.48(d, J = 8 Hz, 1 H) and 5.60 (s, 2H). 76 LCMS (ES)m / z cale, for C25H16CI2FN5O3 523.06; found, 524.1 (M+H), 1H NMR (400 MHz, DMSO-de) δ 13.0 (s,1H), 11.14 (s,1 H), 8.7 (d, J=8.4 Hz, 1H), 8.61 (s , 2H), 7.95 (s, 2H), 7.89-7.83 (m, 2H), 7.67 (d, J=7.6 Hz, 2H), 7.54-7.48 (m, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.13 (t, J= 10.0 Hz, 1H), 5.23 (s, 2H). 77 LCMS (ES) m / zcale, for C25H17CI2N5O3; 505.07; found, 506.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 11.15 (s, 1H), 8.71 (d, J=7.6 Hz, 1H), 8.63 (s, 1H), 8.48-8.44 (m, 1H), 7.92-7.85 (m, 2H), 7.76 (d, J=7.6 Hz, 3H), 7.49-7.44 (m, 3H), 7.29 (t, J = 7.6 Hz, 1H), 6.59 (d, J = 2.4 Hz, 1H), 5.37 (s, 2H). 78 LCMS (ES) m / zcale, for C28H19CI2N3O3, 515.08; found 516.0 (M+H), 1H NMR (400 MHz, DMSO-d6): δ 12.81 (s, 1H), 11.16 (s, 1H), 8.72 (d, J=7.6, 1H), 8.1 (s, 1H) ), 7.90 - 7.87 (m, 3H), 7.46 - 7.38 (m, 8H), 7.32 - 7.30 (m, 4H). 79 LCMS (ES) m / zcalc.C22H16CI2N4O5S,518.02; found, 519.0(M+1). 1H NMR (400 MHz, DMSO d6) δ 13.3 (s, 1H), 8.83 (d, J= 8.0 Hz, 1H), 8.65 (s, 1H), 8.02-8.05 (s, 2H), 7.88 (bs, 1H ), 7.59-7.67 (m, 2H), 7.48 (d, J= 7.2 Hz, 1H), 7.19 (d, J = 6 Hz, 1 H), 5.63 (s, 2H), 3.56 (s, 3H). 80 LCMS (ES) m / zcale, for C21H14CI2N4O3, 440.04; found, 441.1 (M+H); 1H NMR (400 MHz, DMSO-d6) δ 12.87 (s, 1H), 8.68-8.65 (m, 3H), 8.50-8.46 (m, 1H), 7.92-7.79 (m, 4H), 7.41-7.35 (m , 2H), 5.28 (s, 2H). 81 LCMS (ES) m / z cale, for C23H13CI3F3N3O4; 556.9 found 558.0, (M+H); 1H NMR (400 MHz, DMSO-d6) δ 12.83 (s, 1 H), 11.21 (s, 1H), 8.71 -8.68 (m, 2 H), 8.04 (d, J = 8.8 Hz, 1H), 7.86 ( s, 2H), 7.52-7.32 (m, 4H), 5.36 (s, 2 H). 82 LCMS (ES) m / zcale, for C22H13CI2F3N4O3, 508.03; found,509.0 (M+H). 1H NMR (400 MHz, DMSO d6): 12.77 (s, 1H), 11.13 (s, 1H), 8.72-8.66 (m, 2H), 8.60 (s, 1H), 7.92-7.88 (m, 1H) ), 7.84 (s, 2H), 7.74-7.63 (m, 2H), 7.5-7.48 (m, 1H), 5.50 (s, 2H). 83 LCMS (ES) m / z, C26H22CI2N4O5S, Cale, 572.07, found; 571.1 (M-H). 1HNMR(400 MHz, DMSO-d6); δ 12.99 (s, 1H), 11.15 (bs, 1H), 8.72 (d, J= 8.0Hz, 1H), 8.52 (s, 1H), 7.90-7.85 (m, 3H), 7.45 (d, J=7.2 Hz, 1H), 7.38-7.30 (m, 2H), 7.14-7.13 (m, 2H), 5.40 (S, 2H), 3.37 (bs, 4H), 3.25 (bs, 4H). 84 LCMS (ES) m / z cale, for C26H22CI2N4O4 524.1; found, 525.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 13.0 (s,1H), 11.15 (S,1 H), 8.7 (d, J= 8.4 Hz, 1H), 8.54 (s, 1H), 7.89-7.84 (m , 3H), 7.44 (d, J=8.0 Hz, 1H), 7.33-7.31 (m, 2H), 7.11-7.10 (m, 2H), 5.36 (s, 2H), 3.78 (bs, 4H), 2.91 ( bs, 4H). 85 LCMS (ES) m / z cale. for. C26H24CI2F3N3O5, 585.10; found 584.10 [Μ – H]; 1H NMR (400 MHz, DMSO-d6) δ 11.93 (s, 1H), 10.21 (bs, 1H), 9.36 (bs, 1H), 8.28 (d, J = 8.8 Hz, 1H), 7.8 (bs, 2H) , 7.30-7.52 (m, 5H), 7.19 (d, J= 8.8Hz, 1H), 4.55 (d, J= 8.8 Hz, 2H), 4.43(m, 2H), 3.52 (m, 2H), 2.88 ( s, 6H). 86 LCMS (ES) m / zcale, for C24H19CI2F3N2O6, 558.06; found, 557.0 (M-H). 1H NMR (400 MHz, DMSO d6): δ 11.78 (s, 1H), 9.28 (s, 1H), 8.18 (d, J= 9.2 Hz, 1H), 8.12 (s, 1H), 8.04 (s, 2H) , 7.51 (d, J=7.6 Hz, 1H), 7.42-7.31 (m, 4H), 7.21 (d, J = 8.8 112 AND. Spectral data Hz, 1H), 4.89 (s, 1H), 4.56 (d, J= 5.6 Hz, 2H), 4.07 (t, J= 4.8 Hz, 2H), 3.75 (s, 2H). 87 LCMS (ES) m / zcalc. for C22H13CI2F3N4O4, 524.03; found, 525.1 (M+H). 1H NMR (400 MHz, DMSO-ofc); δ 12.79 (s, 1H), 11.16 (bs, 1H), 8.68 (d, J=8 Hz, 1H), 8.59 (s, 1H), 8.27 (d, J= 4 Hz, 1H) 7.92 (d, J = 8 Hz, 1H), 7.85 (t, J= 8 Hz, 3H), 7.44 - 7.37 (m, 2H), 5.28 (s, 2H). 88 LCMS (ES) m / zcalc. for C24H16CI2F3N3O4, 537.05; found, 538.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ, 12.86 (s, 1H), 11.13 (s, 1H), 8.62 (d, J= 7.2Hz, 2H), 7.86 (s, 2H), 7.76 (d, J = 8.4Hz, 1H), 7.50-7.42 (m, 2H), 7.39-7.34 (m, 2H), 5.36 (s, 2H), 3.45 (s, 3H*) [3 methyl proton bound with DMSO solvent peak .]. 89 LCMS (ES) m / zcalc. for C25H18CI2F3N3O4, 551.06; found 552.10 (M+H). 1H NMR (400 MHz, DMSO-cfe) δ, 12.86 (s, 1 H), 11.11 (s, 1 H), 8.62 (d, J = 7.2Hz, 2H), 7.86 (s, 2H), 7.76 (d , J= 8.4Hz, 1H), 7.50-7.42 (m, 2H), 7.39-7.34 (m, 2H) 5.36 (s, 2H), 3.45 (s, 3H*) [6 methyl proton bound with the solvent peak DMSO.]. 90 LCMS (ES) m / zcalc. for C22H12CI3F3N4O4, 557.99; found 559.01 (M+H). 1H NMR (400 MHz, DMSO-ofc) δ, 13.41 (s, 1 H), 11.12(s, 1 H*) hydroxyl proton peak 8.80 (d, J= 9.2Hz, 1H), 8.66 (s, 1H) , 8.02 (t, J= 12.0Hz, 2H), 7.43-7.34 (m, 4H), 5.31 (s, 2H). 91 LCMS (ES) m / zcalc. for C23H15CI2F3N4O4, 538.04; found 539.01 (M+H). 1H NMR (400 MHz, DMSO-cfc) δ, 13.45 (s, 1H), 8.74(d, J= 8.4Hz, 1H), 8.58 (s,1 H), 8.09 (s, 1H), 7.74 (d, J= 8.8Hz, 1H), 7.49-7.42(m, 2H), 7.39-7.32 (m, 2H), 5.33(s, 2H) 3.44(s, 3H*) [3 methyl proton bound with DMSO solvent peak .]. 92 LCMS (ES) m / zcalc. for C22H13CI2F3N4O4, 524.03; found, 525.1 (M+H). 1H NMR (400 MHz, DMSO-d6); δ 12.96 (s, 1H), 11.31 (bs, 1H), 8.86 (d, J= 6 Hz, 1 H), 8.79 (s, 1H), 8.54 (d, J= 5.6 Hz, 1H) 7.88 (s, 2H), 7.50 - 7.35 (m, 4H), 5.36 (s, 2H). 93 LCMS (ES)m / z cale, for C24H16CI2F3N3O5 553.04; found,554.0 (M+H). 1H NMR (400 MHz, DMSO-d6) 512.9 (s, 1H), 11.1 (s, 1H), 8.54 (d, J = 8 Hz, 1H), 7.88 (s, 2H), 7.85-7.81 (m, 1H ), 7.44 - 7.30 (m, 4H), 7.29-7.23 (m, 1 H), 5.27 (s, 2H), 3.56 (s, 3 H). 94 LCMS (ES) m / zcalc. for C24H16CI2F3N3O4, 537.05; found, 538.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 10.39 (S, 1H), 8.45 (S, 1H), 7.97 (s, 2H), 7.75 (d, J= 8.8 Hz, 1H) , 7.57 (d, J= 8.4 Hz, 1H), 7.43-7.29 (m, 3H), 7.17 (d, J= 7.2 Hz, 1H), 5.20 (s, 2H), 2.22 (s, 3H). 95 LCMS (ES) m / z cale, for C22H13CI2F3N4O5, 540.02; found 541.0 (M+H). Purity: 99.27% ​​at 240 nm. 1H NMR (400 MHz, DMSO-d6): δ 12.70 (s, 1H), 12.28 (s, 1H), 11.33 (s, 2H), 8.51 (d, J = 5.6 Hz, 1H), 8.28 (d, J = 6 Hz, 1H), 7.84 (s, 2H), 7.39-7.35 (m, 3H), 5.16 (s, 2H). 96 LCMS (ES): m / z cale, for C23H15CI2F3N4O4; 538.04 found, 539.1 (M+H). 1H NMR (400 MHz, DMSO-oy.· δ 12.98 (s, 1H), 11.33 (s, 1H), 8.86 (d, J = 5.6Hz, 1H), 8.52 (d, J= 5.6Hz, 1H), 7.94-7.84 (m, 2H), 7.49-7.48 (m, 2H), 7.38-7.33 (m, 1H), 7.217.20 (m, 1H), 5.46 (s, 2H), 2.55 (s, 3H). 97 LCMS (ES) m / zcalc.C20H13CI2N3O3S, 445.01; found, 446.0(M+H). 1H), 7.87 (d, J = 7.2 Hz, 1 H), 7.83 (s, 2H), 7.37 (d, J = 4.4 Hz, 5H), 5.29 (s, 2H) 98 LCMS (ES) m / zcalc). .C19H12CI2N4O3S, 446.00; found, 446.8 (M+H). , 7.37 (d, J= 5.6 Hz, 5H), 5.30 (s, 2H). 99 LCMS (ES) m / zcalc. for C20H15CI2N5O3, 443.06 (M+H) d6): δ 11.01 (s, 1H), 10.49 (s, 1H), 8.61 (s, 1H), 7.98 (s, 2H), 7.36-7.28 (m, 5H), 5.13 (s, 2H), 3.89 ( s, 3H). 1 H), 8.67-8.62 (m, 2 H), 8.19 (s, 1 H), 8.05 (d, J=9.6 Hz, 1H), 7.94 (s, 2 H), 7.82-7.79 (m, 1 H ), 7.37 (d, J= 8 Hz, 1 H), 7.31-7.28 (m, 1H), 6.95-6.90 (m, 1 H), 6.51 (s, 1 H), 5.40 (s, 2 H). ΙΛ / tz / zuz ó / unauoo 113 AND. Spectral data 101 LCMS (ES) m / z cale, for C24H15CI2F3N4O3,535.30; found 535.1 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 13.46 (s, 1 H), 8.97 (d, J=8.4 Hz, 1 H), 8.14 (s, 1H), 7.91 (t, J= 8 Hz, 1H ), 7.51-7.46 (m, 2H), 7.33-7.25 (m, 3H), 3.15 (s, 2H), 2.58 (s, 2H), 1.78 (d, J=6.4, 1H), 1.61 (s, 1H ). 102 LCMS (ES) m / z cale, for C24H17CI2N3O3; 465.06; found, 465.9 (M+H). 1H NMR (400 MHz, DMSO-cfe) δ: 13.23 (s, 1H), 11.17 (s, 1H), 8.72 (d, J= 7.6 Hz, 1H), 8.43 (s, 1H), 7.98 (s, 2H ), 7.85 (t, J= 8.4 Hz, 1 H),7.4-7.5(m, 3H), 7.35 (t, J= 7.6 Hz, 2H), 7.27 (t, J=7.2 Hz, 1H), 3.35 ( m, 2H), 1.6-1.8 (m, 2H). 103 LCMS (ES) m / zcale. C21H12CI2F3N3O4S, 528.99; found, 530.1 (M+H). 1H NMR (400 MHz, DMSO efe) δ 11.12 (s, 1H), 10.53 (s, 1H),8.63 (s, 1H), 7.87 (s, 1H), 7.81 (s, 2H), 7.49-7.42 (m , 2H), 7.377 (t, J = 7.6 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H), 5.36 (s, 2H). 104 LCMS (ES) m / zcale. C20H11CI2F3N4O4S, 529.98; found,531.0 (M+H). 1H NMR (400 MHz, DMSO efe) δ11.37 (s, 1H), 8.60 (S, 1H), 8.07 (s, 1H), 7.99 (s, 1H), 7.48-7.43 (m, 2H), 7.39 (m, 1H), 7.26-7.24 (m, 1H), 5.36 (s, 2H). 105 LCMS (ES) m / z cale, for C26H19CI2N5O3; 519.0 found, 520.2 (M+H). 1H NMR (400 MHz, DMSO d6); δ 12.81 (s, 1H), 11.17 (bs, 1H), 8.68-8.67 (m, 1H), 8.31 (s, 1H), 7.84-7.82 (m, 3H), 7.49-7.34 (m, 5H), 7.24 -7.22 (m, 1H), 6.36 (s, 1H), 5.07 (s, 2H), 3.82 (s, 3H). 106 LCMS (ES) m / z cale, for C22H16CI2N4O5S, 518.3; found, 519.1 (M+H). 1H NMR (400 MHz, DMSO d6); δ 12.92 (s, 1H), 8.72 (d, J=8.0 Hz, 1H), 8.44 (s, 1H), 8.00 (s, 1H), 7.98-7.92 (m, 1H), 7.91-7.89 (m, 1H ), 7.71-7.65 (m, 2H), 7.51-7.49 (m, 3H), 7.04-7.01 (m, 1H), 5.68 (s, 2H), 5.52 (s, 2H). 107 LCMS (ES) m / z cale, for C19H14CI2N6O3 444; found, 445.2 (M+H). 1H NMR (400 MHz, DMSO d6); δ 10.05 (bs, 1H), 8.57 (s, 1H), 7.79 (bs, 1H), 7.35 - 7.29 (m, 5H), 5.18 (s, 2H), 3.84 (s, 3H). 108 LCMS (ES) m / zcale, for C23H16CI2N4O3, 466.0; found, 467.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ; 13.32 (s, 1H), 8.51 (d, J= 8.0 Hz, 1H), 8.31 (s, 1H), 8.18-8.15 (m, 2H), 7.76-7.21 (m, 1H), 7.57 (d, J= 8.0 Hz, 2H), 7.32-7.22 (m, 3H), 2.922.90 (m, 2H), 1.72-1.70 (m, 1H), 1.63-1.61 (m, 1H). 109 LCMS (ES) m / zcale, for C23H16CI2N4O3, 466.06; found, 467.2 (M+H). 1H NMR (400 MHz, DMSO-d6) δ; 13.34 (s, 1H), 8.61 (d, J= 8.0 Hz, 1H), 8.33 (s, 1H), 8.1 (bs, 1 H), 7.78-7.72 (m, 2H), 7.59-7.58 (m, 2H ), 7.34-7.24 (m, 4H), 2.93-2.92 (m, 2H), 1.76-1.10 (m, 1H), 1.66-1.61 (m, 1H). 110 LCMS (ES) m / zcale, for C26H17CI2N5O3, 517.0; found 518.1 (M+H), 1H NMR (400 MHz, DMSO-d6): δ 13.45 (s, 1H), 8.80 (d, J= 7.6 Hz, 1H), 8.70-8.69 (m, 1 H), 8.33 (s, 1H), 8.10 (s, 1H), 7.96 -7.94 (m, 1H), 7.82 (t, 1H), 7.73-7.71 (m, 1H), 7.51 -7.48 (m, 1H), 7.44- 7.39 (m, 4H), 7.38-7.19 (m, 1H), 5.37 (s, 2H). 111 LCMS (ES) m / z cale, for C27H18CI2N4O3, 516.0; found 517.1 (M+H), 1H NMR (400 MHz, DMSO-d6); δ 12.86 (s, 1H), 11.10 (bs, 1H) 8.68-8.66 (m, 2H), 8.37 (s, 1H), 7.93.7.90 (m, 1H), 7.84-7.81 (m, 2H), 7.66- 7.64 (m, 1H), 7.50-7.48 (m, 1H), 7.42-7.21 (m, 3H), 7.19-7.06 (m, 1H), 7.06 (s, 1H), 6.93(s, 1H) 5.41 ( s, 2H). 112 LCMS (ES) m / z cale, for C25H15CI2F6N3O4, 605.03; found 604.1 (M-H), 1H NMR (400 MHz, DMSO-d6); δ 12.46 (s, 1H), 11.18 (bs, 1H) 8.77 (d, J =8.8 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.83 (s, 2H), 7.46-7.43 (m , 2H), 7.33-7.24 (m, 2H), 5.40 (s, 2H), 2.68 (s, 3H). 113 LCMS (ES) m / zcale, for C23H15CI2F3N4O5, 554.04; found 553.0 (M-H). 1H NMR (400 MHz, DMSO-efe): δ 13.55 (s, 1H), 8.65 (d, 8 Hz, 1 H), 8.08 (s, 1 H), 7.80 (t, J=8.8 Hz, 1H), 7.38 (s, 2H), 7.29 (s, 2H), 7.23-7.21 (m, 1H), 5.24 (s, 2H), 3.54 (s, 3H). 114 LCMS (ES): m / z cale, for C18H13CI2FN4O3S, 454.01; found 455.1 (M+H). 1H NMR (400 MHz, DMSO- d6): δ 12.32 (s, 1H), 8.37 (m, 1H), 8.10 (s, 1H), 7.46 (m, 1H), 7.35-7.33 (m, 1H), 7.24 -7.18 (m, 3H), 4.62 (d, J= 5.6 Hz, 2H), 2.62 (s, 3 H). ΙΛ / tz / zuz ó / unauoo 114 AND. Spectral data 115 LCMS (ES): m / z cale, for C19H15CI2FN4O3S, 468.02; found 469.1 (M+H). 1H NMR (400 MHz, DMSO-afe): δ 11.91 (s, 1H), 8.38 (d, J=7.2 Hz, 1H), 8.11 (s, 1H), 7.54 (t, J= 8 Hz, 1H), 7.33-7.21 (m, 1H), 7.23-7.18 (m, 3H), 5.45 (m, 1H), 2.59 (m, 3H), 1.54-1.53 ​​(m, 3H). 116 LCMS (ES): m / zcale, for C25H16CI2F3N3O3, 533.05; found 532.1 (M-H). 1H NMR (400 MHz, DMSO-ofe): δ 12.85 (bs, 1H), 11.23 (s, 1H), 8.83 (d, J= 8.4 Hz, 1 H), 7.97 (s, 2H), 7.93 (t, J= 8Hz, 1H), 7.52 (d, J= 8 Hz, 1H), 7.38-7.23 (m, 5H), 3.18-3.17 (m, 1H), 2.65-2.48 (m, 1H), 1.84-1.79 ( m, 1H), 1.68-1.62 (m, 1H). 117 LCMS (ES): m / z cale, for C24H17CI2N5O3, 493.07; found 492.1 (M-H). 1H NMR (400 MHz, DMSO-cfe): δ 13.01 (s, 1H), 11.16 (s, 1H), 8.70 (d, J= 8 Hz, 1H), 8.65 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.88-7.81 (m, 3H), 7.63 (d, J = 8.4 Hz, 1 H), 7.447.39 (m, 2H), 7.20 (t, J= 7.6 Hz, 1 H) , 5.63 (m, 2H), 3.94 (s, 3H). 118 LCMS (ES): m / z cale, for C21H14CI2F3N5O4, 527.04; found 528.1 (M+H). 1H NMR (400 MHz, DMSO-afe): δ 11.00 (s, 1H), 10.47 (s, 1H), 8.53 (s, 1H), 7.93 (s, 2H), 7.41-7.32 (m, 3H), 7.13 (d, 6.8 Hz, 1 H), 5.18 (s, 2H), 3.88 (s, 3 H). 119 LCMS (ES): m / z cale, for C20H13CI2F3N6O4, 528.03; found 529.1 (M+H). 1H NMR (400 MHz, DMSO-afe): δ 10.08 (s, 1H), 8.50 (s, 1H), 7.84 (s, 1H), 7.47-7.40 (m, 2H), 7.37-7.33 (m, 1H ), 7.20-7.17 (m, 2 H), 5.25 (s, 2H), 3.92 (s, 3 H). 120 LCMS (ES): m / z cale, for C20H18CI2F3N3O4, 491.06; found 490.1 (M-H); 1H NMR (400 MHz, DMSO-d6): δ 11.34 (s, 1H), 8.10 (bs, 1H), 7.62 (s, 1H), 7.43-7.33 (m, 4H), 5.1-4.69 (bs, 1H) , 4.47-4.37 (m, 2H), 3.00 (s, 1H), 2.09 (m, 2H), 1.63-161 m, 3 H), 1.47-1.43 (m, 2H); Purity: 98.16% at 240 nm. 121 LCMS (ES) m / zcale. C25H19CI2N3O3,479.08; found, 479.8(M+1); 1H NMR (400 MHz, DMSO α6) δ 12.94 (s, 1H), 11.13 (s, 1H), 8.75 (s, 1H), 8.79 (d, J= 7.6 Hz, 1H), 7.89 (s, 2H), 7.82-7.86 (m, 1H), 7.41 (d, J= 8.0 Hz, 1H), 7.29-7.37 (m, 4H), 7.20-7.23 (m, 1H), 5.33 (q, J= 9.2 Hz, 1H) , 4.20 (q, J= 9.2 Hz, 1H), 2.35-2.6 (m, 3H), 1.94-2.03 (m, 1H). 122 LCMS (ES) m / z cale. C21H13CI3N4O3, 474.01; found, 475.0 (M+1); 1H NMR (400 MHz, DMSO d6) δ 12.79 (s, 1H), 11.3 (s, 1H), 8.71 (d, J= 7.6 Hz, 1H),8.59 (s, 1 H), 8.37-8.39 (m, 1H), 7.84-7.90 (m, 3H), 7.7 (dd, Ji = 1.6 Hz, J1 = 6.0 Hz, 1H), 7.39-7.47 (m, 2H), 5.33 (s, 2H). 123 LCMS (ES) m / zcale. C27H24CI2N4O4, 538.12; found, 539.1 (M+H). 1H NMR (400 MHz, CDCI3) δ 12.89 (s, 1H), 8.90 (d, J= 8.4 Hz, 1H), 8.14 (s, 1H), 8.04 (s, 2H), 7.83-7.79 (m, 1H) , 7.49-7.41 (m, 5H), 6.53-6.50 (m, 1H), 3.97-3.91 (m, 1H), 3.85 (bs, 4H), 3.62-3.57 (m, 1H), 3.20 (s, 2H), 3.04 (bs, 2H), 2.37-2.34 (m, 1H). 124 LCMS (ES) m / zcale. C22H13CI2F3N4O4, 524.03; found, 525.0 (M+H). 1H NMR (400 MHz, DMSO d6) δ 8.76 (s, 1H), 8.52 (d, J = 5.6 Hz, 1H), 8.18 (bs, 1H), 8.04 (s, 2H), 7.66 (bs, 1H), 7.51-7.48 (m, 1H), 7.47-7.39 (m, 2H), 7.37 (d, J= 5.6 Hz, 1H), 5.29 (s, 2H). 125 LCMS (ES) m / zcale. C20H11CI2F6N3O4S, 572.98; found, 572.0 (M-H); 1H NMR (400 MHz, DMSO 06) δ 12.58 (s, 1H), 11.4 (bs, 1H), 9.42 (bs, 1H), 7.85 (s, 2H), 7,387.36 (m, 4H), 4.60 (d , J= 6.4 Hz, 2H). 126 LCMS (ES) m / zcale. C20H16CI2FN3O3S, 467.03; found, 468.0 (M+H); 1H NMR (400 MHz, DMSO c6) δ 11.75(3, 1H), 8.71 (bs, 1H), 7.96 (bs, 2H), 7.47-7.44 (m, 1H), 7.32-7.28 (m, 1H), 7.21 -7.17 (m, 2H), 5.42-5.40 (m, 1H), 2.95 (s, 3H), 1.52 (bs, 3H). 127 LCMS (ES) m / zcale. C19H16CI2F3N3O4, 477.05; found, 478.1 (M+H); 1H NMR (400 MHz, DMSO c at 90 °C) δ 8.15 (bs, 1H), 7.79 (bs, 1H), 7.39-7.27 (m, 4H), 4,754.69 (m, 1H), 4.33 (bs, 2H), 3.77 (bs, 2H), 2.05 (bs, 1H), 1.94-1.89 (m, 3H). 128 LCMS (ES) m / z cale. C20H17CI2F3N2O4, 476.05; found, 477.1 (M+H); 1H NMR (400 MHz, DMSO 06 at 90 °C) δ 10.26 (s, 1H), 8.18 (bs, 1H), 7.49 (bs, 2H), 7.40-7.29 (m, 4H), 4.51-4.58 (m, 1H), 4.41-4.30 (m, 2H), 3.65-3.52 (m, 2H), 2.25-2.19 (m, 1H), 1.99-1.89 (m, 3H). ΙΛ / tZ / ZUZ Ó / UHUUOO 115 AND. Spectral data 129 LCMS (ES) m / z cale, for C20H12CI3N5O3 475.00; found 476.0 (M+H), 1H NMR (400 MHz, DMSO-d6): δ 13.46 (s, 1H), 8.84 (d, J = 8 Hz, 1H), 8.58 (s, 1H), 8.38-8.37 ( m, 1H), 8.12 (s, 1H), 7.87 (t, J = 8.4 Hz, 1H), 7.75 (t, J= 7.6 Hz, 1H), 7.47-7.40 (m, 2H), 5.31 (s, 2H) ) 130 LCMS (ES) m / zcale, for C21H13CI2FN4O3, 458.03; found 459.1 (M+H), 1H NMR (400 MHz, DMSO-d6): δ 12.74 (s, 1H), 11.21 (s, 1H), 8.69 (d, J = 8.4 Hz, 1H), 8.54 (s, 1 H), 8.28 (s, 1H), 7.87-7.77 (m, 4H), 7.43 (d, J= 8 Hz, 2H), 5.47 (s, 2H). 131 LCMS (ES) m / z cale, for C23H15CI2F3N4O4, 538.04; found 539.0 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 8.45 (s, 1H), 8.06 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.46 - 7.39 (m, 2H), 7.36 - 7.32 (m, 1H), 7.22 7.20 (m, 1H), 5.25 (s, 2H), 2.25 (s, 3H); 132 LCMS (ES): m / z cale, for C23H13CI2F4N3O4, 541.02; found, 542.1 (M+H); 1H NMR (400 MHz, DMSO-06): δ 12.59 (s, 1H), 11.16 (s, 1H), 8.64 (s, 2H), 7.84-7.77 (m, 3H), 7.46-7.35 (m, 4H) , 5.34 (s, 2H) 133 LCMS (ES) m / z cale, for C22H12CI2F4N4O4, 542.02; found, 543.0 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 13.28 (s, 1H), 8.80- 8.77 (m, 1H), 8.60 (s, 1H), 8.08 (s, 1H), 7.77 (t, J = 9.6 Hz, 1H), 7.48-7.38 (m, 4H), 5.32 (s, 2H) 134 LCMS (ES):m / zcalc, for C20H18CI2F3N3O4, 491.06; found, 492.1(M+H). 1H NMR (400 MHz, DMSO-cfc): δ 11.57 (bs, 1H), 8.34-8.32 (m, 2H), 7.92 (s, 1H), 7.36121 (m, 3H), 7.19-7.15 (m, 1H) , 4.45-4.23 (m, 3H), 2.87-2.81 (m, 1H), 2.00-1.91 (m, 2H), 1.75-1.60 (m, 4H) 137 LCMS (ES): m / z cale. for. C21H13CI2FN4O3, 572.0; found 459.1 (M+H); 1H NMR (400 MHz, DMSO-d6): <5 12.72 (s, 1H), 11.09 (bs, 1H), 8.62 (d, J= 8.0 Hz, 1H), 8.52 (s, 1H), 8.11 (d , J= 8.0 Hz, 1H), 7.88-7.74 (m, 4H), 7.37 (d. J=8.0 Hz, 1 H), 7.267.3 (m, 1H), 5.27 (s, 2H) 138 LCMS (ES ): m / z cale. for. C20H12CI2FN5O3, 459.03; found 460.1(M+H); 1H NMR (400 MHz, DMSO-d6): δ 13.49 (s, 1H), 8.83-8.81 (m, 1H), 8.59 (s, 1H), 8.18-8.22 (m, 1H), 8.12 (s , 1H), 7.97-7.95 (m, 1H), 7.88-7.84 (m, 1H), 7.44 (d. J=7.6Hz, 1 H), 7.387.34 (m, 1H), 5.28 (s, 2H) 140 LCMS (ES): m / z cale, for C20H12CI2FN5O3, 459.03; found 460.1 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 13.39 (s, 1H), 8.81 (d, J= 8 Hz, 1H), 8.52 (s, 2H), 8.29 (d, J = 4.8 Hz, 1H), 8.08 (s, 1H), 7.87-7.77 (m, 2H), 7.44-7.40 (m, 2H), 5.45 (s, 2H) 141 LCMS (ES): m / z cale, for C24H17CI2F3N4O4, 552.06; found, 553.0 (M+H). 1H NMR (400 MHz, DMSO-ofe): δ 13.43 (s, 1H), 8.72 (d, J= 8Hz, 1H), 8.09 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.48 -7.45 (m, 2H), 7.37- 7.33 (m, 1H), 7.07 (d, J= 7.6 Hz, 1H),5.45 (s, 2H), 2.45 (s, 6H) 142 LCMS (ES): m / z cale, for C24H17CI2F3N4O3, 536.06; found 537.1 [M+H], 1HNMR (400 MHz, DMSO-d6): δ 12.75 (s, 1H), 11.1 (s, 1 H), 8.6-8.67 (m, 1H), 8.59 (d, J = 8.4 Hz, 1H), 7.85-7.83 (m, 2H), 7.76 (d, J = 8.4 Hz, 1H), 7.65-7.63 (m, 2H), 5.57 (s, 2H). 2.36 (s, 6H) 143 LCMS (ES): m / z cale, for C21H13CI3N4O3, 474.01; found 475.0 (M+H). 1H NMR (400 MHz, DMSO-c / 6): δ 12.46 (bs, 1H), 8.74 (d, J= 8.4 Hz, 1 H), 8.45 (s, 1H), 8.38 (d, J= 4.4 Hz, 1H), 8.01 (d, J= 8.4 Hz, 1H), 7.78 (t, J=8 Hz, 1H), 7.60 (s, 2H), 7.38 (t, J = 5.2 Hz, 1 H), 7.33 (d , J = 8 Hz, 1 H), 5.49 (s, 2H) 144 LCMS (ES): m / z cale, for C21H20CI2F3N3O4, 505.08; found, 506.1 (M+H). 1H NMR (400 MHz, DMSO-efe): δ 11.65 (s, 1 H), 8.19-8.13 (m, 2H), 7.19 (s, 1H), 7.24-7.18 (m, 3H), 6.81 -6.77 (m , 1H), 4.40-4.35 (m, 1H), 4.15- 4.09 (m, 1H), 3.96 - 3.94 (m, 1H), 1.86- 1.71 (m, 2H), 1.71 (bs, 2H) 1.53-1.50 ( m, 1H), 1.39-1.30 (m, 2H), 1.24-1.18 (m, 2H). 145 LCMS (ES): m / z cale, for C21H20CI2F3N3O4, 505.08; found, 506.1 (M+H), 1H NMR (400 MHz, DMSO-ofc): δ 11.88 (s, 2H), 8.44 (t, J= 5.6 Hz, 1H), 8.15 (d, J= 8.4 Hz, 1H ), 7.94 (s, 1H), 7.33 - 7.25 (m, 3H), 7.18 - 6.93 (m, 1H), 4.30 (d, J = 4 Hz, 2H), 4.28 - ΙΛ / C / ZUZÓ / UH»UOO 116 AND. Spectral data 4.13 (m, 1H), 2.80 -2.65 (m, 1H), 2.05-2.01 (m, 1H), 2.00 - 1.87 (m, 1H), 1.80 - 1.50 (m, 3H), 1.48 - 1.39 (m , 1H), 1.22 (s, 1H). 146 LCMS (ES): m / z cale, for C24H17CI2F3N4O3, 536.06; found, 537.1 (M+H), 98.67% at 240nm. 1H NMR (400 MHz, DMSO-ofe): δ 12.80 (s, 1H), 11 (bs, 1H), 8.68 (d, J = 4.4 Hz, 1H), 8.55 (d, J = 8 Hz, 1H ), 8.28 (d, J = 7.6 Hz, 1H), 7.82 (s, 2H), 7.73 (d, J = 12 Hz, 1H), 7.59 -7.56 (m, 1H), 5.66 (s, 2H), 2.55 (s, 6H). 147 LCMS (ES): m / z cale, for C23H16CI2F3N5O3, 537.06; found, 538.1 (M+H). 1H NMR (400 MHz, DMSO-cfc): δ 13.30 (s, 1H), 8.71 -8.69 (m, 2H), 8.03 (s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.62 -7.60 (m, 2H), 5.52 (s, 2H), 2.65 - 2.48 (m, 6H) 148 LCMS (ES): m / z cale, for C20H12CI3N5O3 475.1; found 476.1 (M+H), 1H NMR (400 MHz, DMSO-cfe): δ 13.40 (s, 1H), 8.83 (d, J= 8 Hz, 1 H), 8.48 (s, 1H), 8.38 (d , J= 3.2 Hz, 1H), 8.09 (s, 1H), 8.03 (d, J= 6.8 Hz, 1H), 7.86 (t, J= 8.4 Hz, 1H), 7.43 (m, 1H), 7.38 (t , J = 4.8 Hz, 1H), 5.48 (s, 2H) 149 LCMS (ES): m / z cale, for C25H16CI2F5N3O4, 587.04; found, 588.0 (M+H). 1H NMR (400 MHz, DMSO d6): δ 12.58 (s, 1H), 11.15 (s, 1H), 8.72 (d, J = 8 Hz, 1H), 7.887.83 (m, 3H), 7.44-7.37( m, 2H), 7.31-7.27 (m, 1H), 7.18-7.05 (m, 2H), 5.46 (s, 2H), 2.55 (s, 3H) 150 LCMS (ES): m / z cale, for C23H14CI2F4N4O4, 556.03; found, 557.1 (M+H), 1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 8.78-8.74 (m, 1H), 8.06 (s, 1H), 7.75 (t, J = 9.6 Hz, 1H), 7.40 (t, J= 4.8 Hz, 2H), 7.35-7.30 (m, 1H), 7.14-7.12 (m, 1H), 5.42 (s, 2H), 2.44 (s, 3H) 151 LCMS (ES) m / z cale, for C25H18CI2F3N3O3, 535.07; found, 536.01 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 12.81 (s, 1H), 8.59 (d, J= 8.4 Hz, 1H), 7.86 (d. J= 6.4 Hz, 3H), 7.76 (d, J = 8.4 Hz , 1H), 7.60-7.54 (m, 2H), 7.05 (d, J=7.6 Hz, 1H), 5.55 (s, 2H), 2.67 (s, 6H) 152 LCMS (ES) m / z calc.C25H17CI2F4N3O4, 569.05; found, 570.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ 12.71 (s, 1H), 11.13 (s, 1H), 8.64 (d, J = 8.4 Hz, 1H), 7.82 (s, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.41 -7.43 (m, 2H), 7.26-7.30 (m, 1H), 7.09 (d, J= 8.0 Hz, 2H), 5.54 (d, J = 48.0 Hz, 2H), 5.40 ( s, 2H), 2.65 (s, 3H) 153 LCMS (ES) m / zcale, for C23H16C12F3N5O3, 537.06; found, 538.0 (M+H), 1H NMR (400 MHz, DMSO-efe) δ 13.02 (s, 1H), 8.68 - 8.66 (m, 2H), 8.26 (d, J=8 Hz, 1H), 7.78 ( S, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.57 - 7.54 (m, 1H), 5.61 (S, 2H), 2.48 (s, 6H) 154 LCMS (ES) m / z cale, for C23H14CI2F4N4O3, 540.04; found 541.1 (M+H), 1H NMR (400 MHz, DMSO-d6): δ 12.51 (s, 1H), 11.12 (s, 1H), 8.67 (d, J = 4.4 Hz, 1H), 8.58-8.55 ( m, 1H), 8.27 (d, J = 8.0 Hz, 1 H), 7.80-7.73 (m, 3H), 7.58-7.55 (m, 1H), 5.64 (s, 2H), 2.65 (s, 3H) 155 LCMS (ES): m / z cale, for C22H13CI2F4N5O3, 541.03; found 542.1 (M+H). 1H NMR (400 MHz, DMSO-c / 6): δ 13.27 (s, 1 H), 8.76- 8.69 (m, 2H), 8.29 (d, J = 7.6 Hz, 1H), 8.09 (s, 1 H) , 7.79-7.76 (m, 1H), 7.60-7.57 (m, 1H), 5.65 (s, 2H), 2.67 (s, 3H) 156 LCMS (ES): m / z cale, for C24H15CI3F3N3O3, 555.01; found 556.0 (M+H). 1H NMR (400 MHz, DMSO-ofc): <5 12.65 (s, 1H), 8.68 (d, J = 9.2 Hz, 1H), 7.98 (d, J= 9.2 Hz, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.73 (s, 1H), 7.60- 7.50 (m, 3H), 7.14 (d, J = 7.6 Hz, 1H), 5.51 (s, 2H), 2.48 (s, 3H) 157 LCMS ( ES): m / z cale, for C24H15CI3F3N3O3, 569.05; found 568.1 (M-H); 1H NMR (400 MHz, DMSO-cfc): δ 12.63 (s, 1H), 11.16 (s, 1H), 8.56-8.53 (m, 1H), 7.89-7.87 (m, 1H), 7.74-7.68 ( m, 3H), 7.51 -7.47 (m, 2H), 7.32 (s, 1 H), 6.15 (s, 1H), 2.69-2.55 (m, 4H) 158 LCMS (ES): m / z cale, for C24H15CI2F4N3O3 , 539.04; found 540.1 (M+H); 1H NMR (400 MHz, DMSO-ofe): δ12.55 (s, 1H), 11.09 (s, 1H), 8.63-8.60 (m, 1H), 7.85-7.76 (m, 4H), 7.60-7.50 (m, 2H), 7.14-7.12 (d, J = 8 Hz, 1H), 5.52 (s, 2H), 2.48 (s, 3H) 159 LCMS (ES): m / z cale, for C23H14CI2F4N4O3, 540.04; found 541.1 (M+H); 1H NMR (400 MHz, DMSO-ofc): δ 13.24 (s, 1H), 8.78-8.75 (m, 1H), 8.09 (s, 1H), 7.84 (d, J ΙΛ / tZ / ZUZ Ó / UHUUOO 117 AND. Spectral data = 7.2 Hz, 1H), 7.79-7.74 (m, 1H), 7.60-7.50 (m, 2H), 7.13-7.11 (d, J= 8 Hz, 1H), 5.51 (s, 2H), 2.48 ( s,3H) 160 LCMS (ES): m / z cale, for C24H15CI2F5N4O4, 588.04; found 589.1 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 13.26 (s, 1H), 8.87 (d, J = 8 Hz, 1H), 8.09 (s, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.44-7.43 (m, 2H), 7.32-7.28 (m, 1H), 7.16-7.03 (m, 2H), 5.45 (s, 2H), 2.57 (s, 3H) 161 LCMS (ES): m / z cale , for C26H21CI2N5O3, 521.10; found 522.2 (M+H); 1H NMR (400 MHz, DMSO-cfc): δ 13.03 (s, 1H), 11.19 (s, 1H), 8.57 (m, 1H), 8.00 (m, 1H), 7.91 (s, 2H), 7.71 (d , J = 7.6 Hz, 1H) 7.61 (m, 1H), 7.42 (m, 1H), 7.20 (m, 1H), 5.73 (s, 2H), 3.97 (s, 3H), 2.83 (s, 3H), 3H bound in the solvent peak. 162 LCMS (ES): m / z cale, for C25H20CI2N6O3, 522.10; found 523.2 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 13.60 (s, 1H), 8.67 (d, J= 8.4 Hz,1 H), 8.11 (m, 2H), 7.67 (d, J = 8.4 Hz, 1H) , 7.60 (d, J = 8.2 Hz, 1H), 7.41 (m, 1H), 7.16-7.13 (m, 1H), 5.67 (s, 2H), 3.96 (S, 3H), 2.82 (s, 3H), 2.45 (s, 3H) 163 LCMS (ES): m / z cale, for C24H17CI2F3N4O3, 536.06; found 537.1 (M+H); 1H NMR (400 MHz, DMSO-ofe): δ 13.16 (s, 1H), 8.74 (d, J= 8.4 Hz, 1H), 7.92 (s, 1H), 7.86 (d, J=7.6 Hz, 1H), 7.70 (d, J= 8.4 Hz, 1H), 7.61 (t, J= 7.4 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 1 H), 7.03 (d, J = 7.6 Hz, 1H), 5.54 (s, 2H), 2.50 (s, 6H) 164 LCMS (ES): m / z cale, for C24H15CI2F5N4O3, 572.04; found, 573.0 (M+H); 1H NMR (400 MHz, DMSO-c / 6): δ 12.53 (s, 1H), 11.12 (s, 1H), 8.71 -8.65 (m, 2H), 8.28 (d, J = 7.6 Hz, 1H), 7.88 - 7.82 (m, 2H), 7.58 - 7.55 (m, 1H), 7.16 (t, J = 52 Hz, 2H), 5.70 (s, 2H), 2.58 (s,3H) 165 LCMS (ES): m / z cale, for C22H13CI3F3N5O3, 557.00; found 558.01 (M+H); 1H NMR (400 MHz, DMSO-ofc): δ 13.41 (s, 1H), 8.74 (d, J = 8.8 Hz, 1H), 8.67 (d, J = 5.2 Hz, 1H), 8.27 (d, J = 7.6 Hz, 1H), 8.05-7.97 (m, 2H), 7.57 (t, J= 7.6 Hz, 1H), 5.62 (s, 2H), 2.65 (s, 3H) 166 LCMS (ES): m / z cale, for C23H14CI3F3N4O3, 556.01; found, 557.0 (M+H); 1H NMR (400 MHz, DMSO-cfe): δ 12.77 (s, 1H), 11.15 (s, 1H), 8.69- 8.61 (m, 2H), 8.29 (d, J = 7.6 Hz, 1 H), 8.02 ( d, J = 8.8 Hz, 1H), 7.83 (s, 2H), 7.60-7.57 (m, 1H), 5.66 (s, 2H), 2.61 (s, 3H) 167 LCMS (ES): m / z cale, for C25H16CI2F5N3O3, 571.0; found, 572.0 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 12.53 (s, 1H), 11.12 (s, 1H), 8.70 (d, J= 8.8 Hz, 1H), 7.87-7.79 (m, 4H), 7.55-7.46 (m, 2H), 7.26 (t, J=55 Hz, 1 H), 7.09 (d, J = 8 Hz, 1 H), 5.52 (s, 2H), 2.65 (s,3H) 168 LCMS (ES) : m / z cale, for C24H15CI2F4N3O4 555.0; found, 556.1 (M+H); 1H NMR (400 MHz, DMSO-cfc): δ 12.61 (s, 1H), 11.15 (s, 1H), 8.63-8.59 (m, 1H), 7.84 (s, 2H), 7.77 (t, J= 8.0 Hz , 1H), 7.40 (d, J= 4.4 Hz, 2H), 7.34-7.30 (m, 1H), 7.16 (d, J= 7.6 Hz, 1H), 5.44 (s, 2H), 2.51 (s, 3H) 169 LCMS (ES): m / z cale, for C25H15D3CI2F3N3O4, 554.08; found, 555.2 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 12.87 (s, 1H), 11.09 (s, 1H), 8.58 (d, J= 8 Hz, 1H), 7.86 (s, 2H), 7.73 (d, J = 8.8 Hz, 1H), 7.48-7.47 (m, 2H), 7.36-7.32 (m, 1H), 7.11 (d, J = 8.6 Hz, 1 H), 5.46 (s, 2H), 2.51 (s, 3H ) 170 LCMS (ES): m / z cale, for C23H14CI3F3N4O3, 556.01; found, 557.0 (M+H); 1H NMR (400 MHz, DMSO-ofe): δ 13.45 (s, 1H), 8.80 (d, J= 8.8 Hz, 1H), 8.11 (s, 1H), 8.02 (d, J = 9.2 Hz, 1 H) , 7.86 (d, J = 7.2 Hz, 1H), 7.62 - 7.54 (m, 2H), 7.15 (d, J = 7.6 Hz, 1H), 5.53 (s, 2H), 2.48 (s, 3H) (ES): m / z cale, for C24H12D3CI2F4N3O3, 542.06; found, 543.1 (M+H); 1H NMR (400 MHz, DMSO-cfc δ 12.55 (s, 1H), 11.13 (s, 1H), 8.63- 8.60 (m, 1H), 7,857.76 (m, 3H), 7.60-7.50 (m, 2H) , 7.13(d, J= 8.0 Hz, 2H), 5.52 (s, 2H) 172 LCMS (ES): m / z cale, for C23H17CI3N4O3, 502.04; found 503.1 (M+H); -ofc) δ 12.77 (s, 1H), 11.08 (s, 1H), 8.53 (d, J=8.0 Hz, 1H), 8.36 (d, J = 4.4 Hz, 1H), 8.03-8.01 (m, 1H ), 7.82 (d, J = 8 Hz, 2H), 7.70 (d, J = 8 Hz, 1H), oonRhn / cznz / a / υιλι 118 AND. Spectral data 7.40-7.37 (m, 1H), 5.58 (s, 2H), 2.52 (s, 6H) 173 LCMS (ES): m / z cale, for C25H17CI2F4N3O4, 569.05; found 570.1 (M+H); 1H NMR (400 MHz, DMSO-óe) δ 12.62 (s, 1H), 11.16 (s, 1 H), 8.53-8.50 (m, 1H), 7.87-7.84 (m, 1H), 7.71 -7.66 (m, 3H), 7.48-7.43 (m, 2H), 7.30 (s, 1H), 6.11 (bs, 1H), 2.67-2.65 (m, 3H), 1.95 (d, J=6.8, 3H) 174 LCMS (ES) : m / z cale, for C25H17CI2F4N3O4, 569.05; found 570.1 (M+H); 1H NMR (400 MHz, DMSO-ofc) δ 12.64 (s, 1H), 11.15 (bs, 1H), 8.54 (dd, J1 = 4.0 Hz, J2 = 9.2 Hz, 1 H), 7.88 (t, J = 4.4 Hz, 1 H), 7.74 (s, 3H), 7.51 -7.46 (m, 2H), 7.31 (t, J = 4.0 Hz, 1H), 6.15 (bs, 1H), 2.70 (s, 3H), 1.97 ( d, J = 4.0 Hz, 3H) 175 LCMS (ES): m / z cale, for C24H18CI2N4O3, 480.08: found 481.1 [Μ + H]; 1H NMR (400 MHz, DMSO-cfe): δ 13.54 (s, 1H), 8.80 (d. J = 8.0 Hz, 1H), 8.71 (s, 1H), 8.11 (s, 1H), .7.81 (t, J= 8.4 Hz, 1H), 7.05-7.40 (m, 6H), 5.28-5.36 (m, 1H), 4.15-4.22 (m, 1H), 2.3-2.5 (m, 3H), 1.9-2.0 (m, 1H) 176 LCMS (ES)m / zcalc. for C24H14D3CI2F3N4O4 555.08; found, 556.2 (M+H); 1H NMR (400 MHz, DMSO-ofc) δ 13.37 (s, 1H), 8.70 (d, J= 8.0, 1H), 8.04 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.45 ( d, J = 4.8 Hz, 2H), 7.34-7.30 (m, 1H), 7.04 (d, J = 8.0 Hz, 1 H), 5.43 (s, 2H). The 3H methyl protons bind to the DMSO-cfe peak. 177 LCMS (ES) m / z cale, for C23H14CI2F5N5O3, 573.04; found, 574.2 (M+H); 1H NMR (400 MHz, DMSO-ofe) δ 13.26 (s, 1H), 8.82 (d, J= 8.4 Hz, 1H), 8.63 (d, J= 4.4 Hz, 1H), 8.26 (d, J = 7.6, 1H), 8.07 (s, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.56 - 7.53 (m, 1H), 7.12 (t, J = 52 Hz, 1H), 5.66 (s, 2H) , 2.55 (s, 3H) 178 LCMS (ES) m / z cale, for C22H16CI3N5O3, 503.03; found 504.2 (M+H); 1H NMR (400 MHz, DMSO-ofc) δ 13.37 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.40-8.38 (m, 1H), 8.098.03 (m, 2H), 7.71 ( d, J = 8.4 Hz, 1H), 7.42-7.39 (m, 1H), 5.59 (s, 2H), 2.53 (s, 6H) 179 LCMS (ES) m / zcale, for C25H15D3CI2F3N3O3 is 538.09; found, 539.2 (M+H); 1H NMR (400 MHz, DMSO-cfe) δ 12.82 (s, 1H), 11.10 (s, 1H), 8.60 (d, J= 8.4 Hz, 1H), 7.87-7.86 (m, 3H), 7.77-7.75 (m, 1 H), 7.62-7.52 (m, 2H), 7.06 (d, J= 7.6 Hz, 1 H), 5.55 (s, 2H), 2.33 (s,3H) 180 LCMS (ES) m / z cale, for C24H14D3CI2F3N4O3 is 539.08; found, 540.2 (M+H); 1H NMR (400 MHz, DMSO-c / 6) δ 13.39 (s, 1H), 8.71 (d, J = 8.4 Hz, 1H), 8.07 (s, 1H), 7.84 (d, J= 7.2 Hz, 1H) , 7.72 (d, J = 8.8 Hz, 1H), 7.61-7.50 (m, 2H), 7.02 (d, J = 7.6 Hz, 1H), 5.52 (s, 2H), 2.46 (s, 3H) 181 LCMS ( ES) m / zcale, for C24H15CI2F5N4O3, 572.04; found, 573.2 (M+H); 1H NMR (400 MHz, DMSO d6) δ 13.12 (s, 1H), 8.88 (d, J= 8.8 Hz, 1H), 8.0-7.9 (m, 1H), 7.82 (d, J = 8.8 Hz, 1 H) , 7.58 - 7.48 (m, 2H), 7.11 (t, J = 55 Hz, 1H), 7.07 (d, J = 8.8 Hz, 2H), 5.55 (s, 1H), 2.68 (s, 3H) 182 LCMS (ES) m / z cale. C19H12CI2F3N3O3S, 488.99; found, 488.1(M-1); 1H NMR (400 MHz, DMSO d6) δ 12.14 (s, 1H), 9.23 (s, 1H), 8.69 (s, 1H), 7.76-7.64 (m, 4H), 7.53 - 7.46 (m, 2H), 4.75 (d, J = 6.0 Hz, 2H) 183 LCMS (ES) m / z cale, for C23H17CI2FN4O3, 486.07; found 487.2 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 12.76 (s, 1H), 8.54 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 4.8 Hz, 1H), 7.83-7.79 (m, 3H ), 7.71 (d, J= 8.4 Hz, 1H), 7.45-7.43 (m, 1H), 5.59 (s, 2H), 2.55 (s, 3H), 2.43 (s, 3H) [buried under DMSO peak ] 184 LCMS (ES) m / zcalc.C23H11D3CI2F4N4O3, 543.0; found, 543.1 (M+1); 1H NMR (400 MHz, DMSO d6) 512.81 (s, 1H), 8.81 (dd, J1 = 4.8 Hz, J2 = 9.6 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.75 (s, 1H ), 7.69 (t, J = 9.6 Hz, 1H), 7.63 - 7.52 (m, 2H), 7.11 (d, J = 7.6 Hz, 1H), 5.53 (s, 2H) 185 LCMS (ES) m / zcale. C19H12CI2F3N3O3S, 488.99; found, 488.1(M-1); 1H NMR (400 MHz, DMSO 06) 5 12.14 (s, 1H), 9.23 (s, 1H), 8.69 (s, 1H), 7.76-7.64 (m, 4H), 7.53 - 7.46 (m, 2H), 4.75 (d, J = 6.0 Hz, 2H) 186 LCMS (ES) m / z cale. for. C25H17CI2F4N3O3, 553.06; found 554.2 (M+H); 1H NMR (400 MHz, DMSO-ofc) 5 12.68 (s, 1H), 11.10 (s, 1 H), 8.67 (d, J= 8.4 Hz, 1H), 7.79- ΙΛ / C / ZUZÓ / UH»UOO 119 AND. Spectral data 7.89 (m, 4H), 7.49-7.58 (m, 2H), 7.08 (d, J= 7.2 Hz, 1 H), 5.59 (s, 2H), 5.50 (d, J= 16.4 Hz, 2H) 2.61 (S,3H) 187 LCMS (ES) m / z cale. C19H14CI2N6O3S 476.02; found 475.2 (M-H); 1H NMR (400 MHz, DMSO-d6): δ 12.83 (s, 1H), 9.05 (t, J = 6 Hz, 1H), 8.72 (s, 1H), 8.13 (s, 1 H), 7.93 (d, J= 8 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.40-7.36 (m, 1H), 7.13-7.08 (m, 1H), 4.88 (d, J=6Hz, 2H), 4.01 (s, 3H) 188 LCMS (ES) m / z cale. C19H14CI2N5O3S 475.03; found 475.0 (M-H), 1H NMR (400 MHz, DMSO-d6): δ 12.45 (s, 1H), 11.34 (bs, 1H), 9.21 (t, J = 6 Hz, 1H), 8.69 (s, 1H) , 7.89 (d, J= 8.0 Hz, 1H), 7.84 (s, 2H), 7.56 (d, J= 8.8 Hz, 1H), 7.36 (t, J= 8 Hz, 1H), 7.18 (s, 1H) , 7.10-7.06 (m, 1H), 4.85 (d, J= 6 Hz, 2H), 3.98 (s, 3H) 189 LCMS (ES) m / z cale, for C17H11CI2FN4O3S 439.99; found, 441.1 (M+H), 1H NMR (400 MHz, DMSO-ofe) δ 12.78 (s, 1H), 9.20 (s, 1H), 8.74 (s, 1H), 8.14 (s, 1H), 7.397 .35 (m, 1H), 7.20-7.14 (m, 3 H), 4.56 (d, J = 5.6 Hz, 2H) 190 LCMS (ES) m / z cale, for C25H18CI2FN5O3, 525.08; found 526.2 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 12.76 (s, 1H), 11.21 (s, 1H), 8.62 (dd, Ji = 4.4 Hz, J2 = 4.4 Hz, 1H), 8.02 (d, J = 8 Hz, 1H), 7.91 (s, 2H), 7.75 (t, J = 10 Hz, 1H), 7.63-7.61 (m, 1H), 7.45-7.42 (m, 1H), 7.23-7.19 (m, 1H) , 5.73 (s, 2H), 3.98 (s, 3H), 2.85 (s, 3H) 191 LCMS (ES) m / z cale, for C18H11CI2F3N4O4S, 505.98; found, 507.0(M+H). 1H NMR (400 MHz, DMSO-d6) δ 12.73 (s, 1H), 9.15 (t, J=6.2, 1H), 8.74 (s, 1H), 8.12 (s, 1H), 7.41 -7.35 (m, 4H ), 4.58 (d, J=6.4 Hz, 2H) 192 LCMS (ES) m / zcale. C18H11CI2F3N4O3S, 489.99; found, 489.1 (M-1); 1H NMR (400 MHz, DMSO d6) δ 12.44 (s, 1H), 9.06 (t, J= 6.0 Hz, 1H), 8.67 (s, 1H), 7.90 (s, 1H), 7.75 (d, J = 8.0 Hz, 1 H), 7.65 (d, J = 7.6 Hz, 1H), 7.53 - 7.46 (m, 2H), 4.73 (d, J = 4.0 Hz, 2H) 193 LCMS (ES) m / zcale, for C17H10CI2F3N5O3S , 490.98; found, 490.1 (M-H); 1H NMR (400 MHz, DMSO-d6): δ 12.54 (s, 1H), 9.21 (t, J = 6 Hz, 1H), 8.69 (s, 1H), 8.05 (t, J = 8 Hz, 1 H) , 7.96 (s, 1H), 7.78 (d, J = 7.6 Hz, 1 H),7.64 (d, J = 7.6 Hz, 1 H), 4.69 (d, J = 5.6 Hz, 2H) 194 LCMS (ES) m / z cale, for C24H17CI2FN6O3, 526.07; found 525.2 (M-H); 1H NMR (400 MHz, DMSO-d6): δ 13.45 (s, 1H), 8.76-8.73 (m, 1H), 8.14-8.10 (m, 2H), 7.72 (t, J = 8 Hz, 1H), 7.61 (d, J= 8 Hz, 1H), 7.42 (t, J= 6.8 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 5.70 (s, 2H), 3.99 (s, 3H), 2.86 (s, 3H) 195 LCMS (ES) m / z cale, for C22H16CI2FN5O3, 487.06; found 488.2 [M+H], 1HNMR (400 MHz, DMSO-d6): δ 13.35 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 4.4 Hz, 1H), 8.07 (s, 1H), 7.82 (t, J= 9 Hz, 1H), 7.70 (d, J=8.4 Hz, 1 H), 7.46-7.42 (m, 1H), 5.58 (s, 2H), 2.59 ( s, 3H), 2.35 (s, 3H) 196 LCMS (ES) m / z cale, for C17H10CI2F3N5O3S, 490.98; found 492.1 [M+H], 1H NMR (400 MHz, DMSO-d6): δ 12.66 (s, 1H), 8.95 (t, J= 5.4 Hz, 1H), 8.85 (d, J = 4.8 Hz, 1H) , 8.74 (s, 1H), 8.23 ​​(d, J = 7.6 Hz, 1H), 8.08 (s, 1H), 7.60-7.57 (m, 1H), 4.87 (d, J=5.2 Hz, 2H) 197 LCMS ( ES) m / z cale, for C23H14CI2F4N4O3, 540.04; found, 541.1 (M+H), 1H NMR (400 MHz, DMSO-c / 6) δ 12.53 (s, 1H), 11.14 (s, 1 H), 8.62-8.59 (m, 1H), 8.13 (t, J = 15.9 Hz, 1H), 7.90-7.75 (m, 5H), 5.61 (s, 2H), 2.63 (s, 3H) 198 LCMS (ES) m / z cale, for C18H11CI2F3N4O3S is 489.99; found, 489.0 (M+H), 1H NMR (400 MHz, DMSO-Ó6) δ 12.31 (s, 1H), 11.33 (bs, 1H), 9.36 (t, J= 5.6 Hz, 1H), 8.75 (s, 1H), 8.07 (t, J = 8 Hz, 1H), 7.82-7.79 (m, 3H), 7.68 (d, J = 8 Hz, 1H), 4.73 (d, J = 6 Hz, 2H) 199 LCMS (ES): m / z C24H17CI2F3N4O3 cale, for 536.06; found, 537.1 (M+H). 1H NMR (400 MHz, DMSO-d6): 12.77 (s, 1H), 11.10 (bs, 1 H), 8.54 (d, J = 8.4, 1H), 8.09 (t, J = 7.6 Hz, 1 H), 7.83 - 7.81 (m, 3H), 7.76 (d, J = 8 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1 H), 5.57 (s, 2H), 2.60 (s, 3H) 2.48* ( s, 3H) (bound with DMSO peak) 200 LCMS (ES): m / z cale, for C25H16D2CI2F3N3O3, 537.08; found, 538.1 (M+H). ΙΛ / tz / zuz ó / unauoo 120 AND. 1H NMR spectral data (400 MHz, DMSO-d6): δ 12.82 (s, 1H), 11.08 (bs, 1H), 8.60 (d, J= 8.4 Hz, 1H), 7.87 (m, 3H), 7.75 (d , J= 8.4 Hz, 1H), 7.62-7.52 (m, 2H), 7.06 (d, J= 7.6Hz, 1H), 2.52* (s, 3H), 2.48*(s, 3H) (*joined with the DMSO peak) 201 LCMS (ES) - m / z cale, for C24H15D2CI2F3N4O3 is 538.08; found, 539.4 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 13.39 (s, 1H), 8.71 (d, J= 8.4Hz, 1H), 8.07 (s, 1H), 7.85 (d, J= 7.2Hz, 1H), 7.72 (d, J = 8.4Hz, 1H), 7.61-7.57 (m, 1H), 7.54-7.50 (m, 1H), 7.02 (d, J = 7.6Hz, 1H), 2.48 (s, 3H), 2.45 (s, 3H) 202 LCMS (ES): m / z cale, for C26H22CI2N4O3, 508.11; found 509.1 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 13.69 (s, 1H), 8.66 (d, J= 8.4 Hz, 1H), 8.12 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.35-7.30 (m, 4H) 7.24-7.20 (m, 1H), 4.97-4.79 (m, 2H), 2.42 (s, 6H), 2.38-2.31 (m, 3H), 2.07-1.96 (m, 1H) 203 LCMS (ES): m / z cale, for C27H23CI2N3O3, 507.11; found 508.2 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 13.00 (s, 1H), 11.09 (bs, 1H), 8.52 (d, J = 8.4 Hz, 1H), 7.95 (s, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.36-7.30 (m, 4 H), 7.24-7.21 (m, 1H), 5.0-4.93 (m, 1H), 4.81 -4.74 (m, 1H), 3.27-3.20 (m, 1H), 2.40-2.25 (m, 8H), 2.09-1.90 (m, 1H) 204 LCMS (ES): m / z cale, for C23H13CI2F4N3O3, 525.03; found, 524.1 (M-H); 1H NMR (400 MHz, DMSO-d6): δ 12.51 (s, 1H), 11.08 (bs, 1H), 8.66-8.63 (m, 2H), 7,837.78 (m, 4H), 7.60-7.49 (m, 2H), 7.17 (d, J = 7.2Hz, 1 H), 5.46 (s, 2H) 205 LCMS (ES): m / z cale, for C23H16CI2F3N5O3, 537.06; found, 538.1 (M+H); 1H NMR (400 MHz, DMSO o6): δ 13.33 (s, 1H), 8.67 (d, J = 8.4 Hz, 1H), 8.12 - 8.05 (m, 2H), 7.83 (d, J= 8 Hz, 1H) , 7.75 (d, J= 8 Hz, 1H), 7.69 (d, J= 8.8 Hz, 1H), 5.54 (s, 2H), 2.59 (s, 3H), 2.48* (s, 3H), (* joined with DMSO peak) 206 LCMS (ES): m / z cale, for C22H12CI2F4N4O3 is 526.02; found 527.0 (M+H); 1H NMR (400 MHz, DMSO-d6): δ 13.23 (s, 1H), 8.81-8.78 (m, 1H), 8.60 (s, 1H), 8.08 (s, 1H), 7.82-7.77 (m, 2H ), 7.61-7.57 (m, 1H), 7.53-7.49 (m, 1H), 7.17 (d, J = 7.6Hz, 1H), 5.44 (s, 2H) 207 LCMS (ES): m / z cale, for C25H19CI2FN4O3, 512.08; found 513.1 (M+H); 1H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 8.72-8.68 (m, 2H), 8.12 (s, 1H), 7.70-7.65 (m, 1H), 7.35-7.28 (m, 3H ), 7.22-7.19 (m, 1H), 4.95-4.90 (m, 1H), 4.81-4.76 (m, 1H), 2.36 (s, 3H), 2.33-2.25 (m, 2H), 2.01 -1.96 (m , 2H) ΙΛ / C / ZUZÓ / UHUUOO Example A: Estrone Detection Assay for Evaluation of HSD17B13 Activity and Identification of Inhibitors The liquid chromatography / mass spectrometry (LC / MS) estrone detection assay monitors the conversion of estradiol to estrone by HSD17B13. This assay was carried out in a 96wp format (Eppendorf 96 / 500 deep well plate) in a reaction volume of 80 μΙ containing: 4 μΜ Estradiol (E2; Cayman; #10006315), 6 mM NAD (Sigma; #N0623) and 30 nM HSD17B13 enzyme (internal; soluble, purified, His-tagged protein expressed in E. coli) in a reaction containing 1 M potassium phosphate buffer, pH 7.4, with 0.5% vehicle (DMSO). Reactions were incubated for 2 hours at 26.5°C, and the conversion of estradiol (E2) to estrone (E1) was quantified by LC-MS / MS-based analyte detection for E2 and E1 using LCMS-grade reagents. Reactions were terminated by adding two volumes of acetonitrile (MeCN; LCMS grade; CAS# 75 / 05 / 8) containing deuterated (D4)-E1 used as standard 121 internal (Clear Synth; #CS-T-54273; 500 ng / ml final concentration). Samples were applied to prepared Extraction Bond Elut-C18 cartridges (3 mL; Agilent; #12102028), washed, and eluted in MeCN. Eluates were dried under nitrogen and resuspended in 60% methanol (LCMS grade methanol; CAS# 67 / 56 / 1) before being sent for analysis. The aqueous linearity for E2 and E1 were included for quantification. Sample analysis was performed on an Q (mobile phase B) in a 3min gradient allowing 25%B. Analytes were detected in negative mode using MRM analysis, with E2 having an RT of 1.85 min and E1 having an RT of 2 min. The activity of the enzyme, in the absence of NAD+, was used to evaluate the specificity of the conversion. Enzyme activity in the presence of test samples was expressed as a percentage of uninhibited enzyme activity and plotted against inhibitor concentration. Nonlinear regression was performed using a four-parameter logistic model and GraphPad Prism software (GraphPad Software, La Jolla, CA). All evaluations were performed in duplicate and pooled during the extraction process and subsequently injected as duplicates for LC-MS / MS analysis. The data is shown in table 2 below: Table 2: Ex· IC50 with estradiol Ex· IC50 with estradiol 1 B 103 B 2 A 104 B 3 B 105 B 4 D 106 Y 5 B 107 C 6 A 108 C 7 B 109 D 8 B 110 B 9 B 112 B 10 A 113 B 11 A 114 B 12 A 115 B 13 C 116 B 14 D 117 A 15 C 118 C 16 B 119 B 17 D 120 D 18 A 121 B 19 B 122 B 20 D 123 B 21 A 124 D 22 A 125 B 23 B 126 A 24 D 127 Y 25 B 128 Y 122 AND. IC5o with estradiol E!. IC50 with estradiol 26 B 129 B 27 B 130 B 28 D 131 B 29 B 132 A 30 C 133 B 31 B 134 C 32 A 137 B 33 B 138 B 34 A 140 B 35 A 141 A 36 B 142 B 37 A 143 A 38 B 144 Y 39 D 145 D 40 B 146 A 41 A 147 B 42 B 148 B 43 A 149 A 44 A 150 A 45 D 151 A 47 A 152 C 48 B 153 B 49 B 154 A 50 B 155 B 51 B 156 A 52 C 157 B 53 A 158 A 54 D 159 B 56 C 160 A 57 B 162 B 58 B 163 B 59 D 164 B 60 C 165 B 61 B 166 B 62 B 167 A 63 B 168 A 64 A 169 A 65 D 170 B 66 B 171 B 67 A 172 B 68 B 173 B 69 B 174 B 70 B 175 B 71 B 176 A 72 B 177 B 73 B 178 C 74 B 179 A 75 A 180 B 76 A 181 B 77 B 182 A oonRHn / cznz / a / υιλι 123 AND. IC5o with estradiol E!. IC50 with estradiol 78 A 183 B 79 C 184 B 80 C 185 A 81 A 186 A 82 A 187 B 83 D 188 A 84 A 189 B 85 Y 190 A 86 B 191 A 87 B 192 B 88 A 193 C 89 A 194 B 90 B 195 D 91 B 196 B 92 B 197 C 93 A 198 C 94 B 199 C 95 B 200 A 96 A 201 B 97 B 202 B 98 B 203 A 99 D 204 A 100 B 205 C 101 D 206 A 102 D 207 B IC50with estradiol A is less than or equal to 0.1 μΜ; B is greater than 0.1 μΜ and less than or equal to 0.5 μΜ; C is greater than 0.5 μΜ and less than or equal to 1.0 μΜ; D is greater than 1.0 μΜ and less than or equal to 10 μΜ; E is more than 10 μΜ; NT: not tested

Claims

1. A compound of Formula (I), or one of its pharmaceutically acceptable salts, solvates, or stereoisomers: L—ra (R5)n Formula (I), characterized in that: Cl IL / ó / unyuoo ring B is Cl r1 ozz ; Yes N oCR1; each Z is independently N o CR1; each R1 is independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; L is -O-, -C(=O)NR3-, -NR3C(=O)-, -C(=O)C(R4)2-, or -C(R4)2C(=O)-; R3 is hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or CrCe deuteroalkyl; each R4 is independently hydrogen, deuterium, halogen, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; ring A is a 3- to 12-membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S, N, P, and B; each R5 is independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl;or two R5 on the same atom join to form an oxo; n is 0-6; RA is: (a) -C(=O)NR10R11; or (b) C4-C10 alkyl optionally substituted with one or more RAa; or (c) -(C(R12)2)pCycloalkyl, -(C(R12)2)pheterocycloalkyl, -(C(R12)2)paryl, or (C(R12)2)pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAb; R10 and R11 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl, C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, C1-C10 heteroalkyl, C2-Cw alkenyl, C2-Cw alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C6-C6 alkyl (cycloalkyl), C6-C6 alkyl (heterocycloalkyl), C1-C6 alkyl (heteroaryl), or C6-C6 alkyl (heteroaryl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10a;each R10a is independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS(=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C(=O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, deuteroalkyl Ci-Ce, hydroxyalkyl of Ci-Ce, aminoalkyl of Ci-Ce, Ci-Ce heteroalkyl, C2-Ce alkenyl, C2-Ce alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more R10b; or two R10a on the same atom are joined together to form an oxo;each R10b is independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS(=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C(=O)NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, aminoalkyl C1-Ce, C1-Ce heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; that of R10b in the same atom come together to form an oxo; each RAa is independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS(=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C(=O)NRcRd, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;wherein each alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAa on the same atom join together to form an oxo; each RAb are independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS(=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C(=O)NRcRd, Ci-C6 alkyl, Ci-C6 haloalkyl, deuteroalkyl Ci-Ce, hydroxyalkyl of Ci-Ce, aminoalkyl of Ci-Ce, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2-Ce alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more RAaa; or two RAb on the same atom join together to form an oxo;ΙΛ / tz / zuz ó / unauoo 126 each RAaa is independently deuterium, halogen, -CN, -NO2, -OH, -ORa, OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NHS(=O)2Ra, -C(=O)Ra, C(=O)C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, -C(=O)C(=O)NRcRd, Ci-C6 alkyl, C1-C6 haloalkyl, C1-Ce deuteroalkyl, C1-Ce hydroxyalkyl, C1-Ce aminoalkyl, C1-Ce heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; each R12 is independently hydrogen, deuterium, halogen, C1-Ce alkyl, C1-C6 haloalkyl, C1-C6 deuteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; that of R12 on the same carbon come together to form a cycloalkyl or a heterocycloalkyl;wherein the cycloalkyl and heterocycloalkyl are optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-Cs haloalkyl, Ci-Ce deuteroalkyl, or two R12 on the adjacent carbon join together to form a cycloalkyl optionally substituted with deuterium, halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl; p is 1-4; each Ra is independently Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1Ce alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or Ci-C6 alkyl (heteroaryl);wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2i -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1C& aminoalkyl, or Ci-Ce heteroalkyl; each Rb is independently hydrogen, Ci-Cs alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C6 alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or Ci-C6 alkyl (heteroaryl);wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3j -C(=O)OH, -C(=O)OCH3, C1Cq alkyl, CrCe haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Ce aminoalkyl, or Ci-Ce heteroalkyl; and oonRHn / cznz / a / υιλι 127 each Rc and Rd are independently hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-Ce alkyl (Cecycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or Ci-C6 alkyl (heteroaryl);wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is optionally and independently substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OCH3, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, C1Cq aminoalkyl, or Ci-Cs heteroalkyl; or Rc and Rd are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, OCH3, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, N(CH3)2, -C(=O)CH3i -C(=O)OH, -C(=O)OCH3j alkyl of Ci-C6, haloalkyl of Ci-C6, deuteroalkyl of Ci-Ce, hydroxyalkyl of Ci-Ce, aminoalkyl of Ci-Ce, or heteroalkyl of C1C6;provided that the compound is not ci ΗΟ ΗΟ ΗΟ Cl ci Cl ΗΟ Cl Cl 128 oonRhn / cznz / a / υιλι 129 HO—é Λ— NH Cl Λ / tz / zuz ó / unauoo; 2. The compound according to claim 1, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that the compound of Formula (I) is of Formula (a): Formula (a).

3. The compound according to claim 1 or 2, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: Y is n.

4. The compound according to claim 1 or 2, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: YesCR1.

5. The compound according to claim 1, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that the compound of Formula (I) is of Formula (Ib): Formula (Ib).

6. The compound according to claim 1, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that the compound of Formula (I) is of Formula (le): HO Cl Formula (le).

7. The compound according to claim 1 or 6, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: one Z is CR1 and one Z is N.

8. The compound according to claim 1 or 6, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: 130 each Z is GR1.

9. The compound according to claim 1, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that the compound of formula (I) has the formula (Id): oonRhn / cznz / a / υιλι HO OI Formula (Id).

10. The compound according to any one of claims 1-9, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: each R1 is hydrogen.

11. The compound according to any one of claims 1-10, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: L is -C(=O)NR3-.

12. The compound according to any one of claims 1-11, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: R3 is hydrogen.

13. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: ring A is a 3- to 6-membered ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S or N.

14. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: ring A is an 8- to 12-membered bicyclic ring optionally comprising 1 to 4 heteroatoms selected from the group consisting of O, S or N.

15. The compound according to any one of claims 1-9, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: ring A is phenyl or a 5- or 6-membered heteroaryl.

16. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: ring A is a 5-membered heteroaryl.

17. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: ring A is a 6-membered heteroaryl.

18. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: 131 ring A is thiophene, thlazole, isothiazole, oxazole, isoxazole, phenyl, pyridine or pyrimidine.

19. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: ring A is thiazole, isothiazole, oxazole, isoxazole, phenyl, pyridine or pyrimidine.

20. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: ring A is dihydroquinazoline, isoindoline or 2,3-dihydrobenzooxazepine.

21. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that:

22. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: OR 23. The compound according to any one of claims 1-22, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: each R5 is independently hydrogen, deuterium, halogen or Oι-Oθ alkyl; or two R5 on the same atom join together to form an oxo.

24. The compound according to any one of claims 1-23, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: n is 0-4.

25. The compound according to any one of claims 1-24, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: n is 0-2.

26. The compound according to any one of claims 1-25, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: 132 n is 0 or 1.

27. The compound according to any one of claims 1-26, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: n is 1.

28. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl.

29. The compound according to any one of claims 1-12, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-C6 alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl.

30. The compound according to claim 28 or 29, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: R5a is deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5b, R5c, and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl.

31. The compound according to claim 28 or 29, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: R5b is deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5a, R5c, and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl.

32. The compound according to claim 28 or 29, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: R5c is deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5a, R5b, and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl.

33. The compound according to claim 28 or 29, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: R5d is deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; and R5a, R5b, and R5d are independently hydrogen, deuterium, halogen, -CN, -OH, -ORa, -SH, -SRa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl.

34. The compound according to any one of claims 1-33, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: RA is -C(=O)NR10R11.

35. The compound according to any one of claims 1-34, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: R11 is hydrogen.

36. The compound according to any one of claims 1-35, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: R10 is C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 deuteroalkyl, C1-C10 hydroxyalkyl, C1-C10 aminoalkyl, C1-C10 heteroalkyl, Ci-C6 alkyl (cycloalkyl), Ci-C6 alkyl (heterocycloalkyl), Ci-C6 alkyl (aryl), or Ci-C6 alkyl (heteroaryl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one or more R10a.

37. The compound according to any one of claims 1-36, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: R10 is a C1-C10 alkyl optionally substituted with one or more R10a.

38. The compound according to any one of claims 1-37, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: R10 is a Ci-C6(aryl) alkyl wherein the aryl is optionally substituted with one or more R10a.

39. The compound according to any one of claims 1-38, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, characterized in that: each R10a is independently deuterium, halogen, -CN, -OH, -ORa, -NRcRd, C(=O)Ra, -C(=O)Ob, -C(=O)NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, C1Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, Ci-Ce heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one or more R10b 40. The compound according to any one of claims 1-39, or a pharmaceutically acceptable version of its salts, solvates, or stereoisomers, characterized in that: each R10a is independently deuterium, halogen, -CN, -OH, -ORa, -NRcRd, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce deuteroalkyl, Ci-Ce hydroxyalkyl, Ci-Ce aminoalkyl, or Ci-Ce heteroalkyl; wherein each alkyl is optionally and independently substituted with one or more R10b 41. The compound according to any one of claims 1-40, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: each R10a is independently deuterium, halogen, -OH, -ORa, Ci-Ce alkyl, Ci-Ce haloalkyl, or Ci-Ce deuteroalkyl; wherein each alkyl is optionally and independently substituted with one or more R10b.

42. The compound according to any one of claims 1-33, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: RA is a C4-C10 alkyl optionally substituted with one or more RAa.

43. The compound according to any one of claims 1-33, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, characterized in that: RA is -(C(R12)2)pCycloalkyl, -(C(R12)2)pheterocycloalkyl, -(C(R12)2)Paryl, or (C(R12)2)pheteroaryl; wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are optionally and independently substituted with one or more RAb groups.

44. The compound according to any one of claims 1-33 or 43, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: RA is -(C(R12)2)Paryl or -(C(R12)2)Pheteroaryl; characterized in that the aryl and heteroaryl groups are optionally and independently substituted with one or more RAb groups.

45. The compound according to any one of claims 1-33 or 43 or 44, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: RA is -(C(R12)2)Par¡lo; wherein the aryl is optionally and independently substituted with one or more RAb.

46. ​​The compound according to any one of claims 1-33 or 43-45, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: each R12 is independently hydrogen, deuterium, halogen or Ci-Ce alkyl; or two R12 on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl.

47. The compound according to any one of claims 1-33 or 4346, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: each R12 is hydrogen or two R12 on the same carbon join together to form a cycloalkyl.

48. The compound according to any one of claims 1-33 or 4346, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: each R12 is hydrogen or two R12s on adjacent carbon join together to form a cycloalkyl.

49. The compound according to any one of claims 1-33 or 4348, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: each R12 is hydrogen.

50. The compound according to any one of claims 1-33 or 4348, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: two R12 groups on the same carbon are joined together to form a cycloalkyl group.

51. The compound according to any one of claims 1-33 or 4348, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: two R12 groups on adjacent carbons join together to form a cycloalkyl group.

52. The compound according to any one of claims 1-33 or 4351, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: p is 1 or 2.

53. The compound according to any one of claims 1-33 or 4352, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: p is 1.

54. The compound according to any one of claims 1-33 or 4352, or one of its pharmaceutically acceptable salts, solvates or stereoisomers, characterized in that: p is 2.

55. A compound selected from a compound characterized in that it is found in Table 1, or one of its pharmaceutically acceptable salts, solvates or stereoisomers.

56. A pharmaceutical composition characterized in that it comprises a compound of any one of claims 1-55, or one of its pharmaceutically acceptable salts, solvates, or stereoisomers, and a pharmaceutically acceptable carrier. oonRhn / cznz / a / uili 136 57. A method for treating a disease in a subject in need thereof, the method being characterized in that it comprises administering a pharmaceutically effective amount of a compound of any of claims 1-55, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, or a pharmaceutical composition of claim 56.

58. The method according to claim 57, characterized in that the disease is a liver disease, a metabolic disease, or a cardiovascular disease.

59. The method according to claim 57 or 58, characterized in that the disease is NAFLD.

60. The method according to claim 57 or 58, characterized in that the disease is NASH.

61. The method according to claim 57 or 58, characterized in that the disease is drug-induced liver injury (DILI).

62. The method according to claim 57 or 58, characterized in that the disease is associated with HSD17B13.

63. The method according to claim 57 or 58, characterized in that the disease is alcoholic liver disease.

64. The method according to claim 57 or 58, characterized in that the disease is cirrhosis.

65. The method according to claim 57 or 58, characterized in that the disease is decompensated portal hypertension.

66. The method according to claim 57 or 58, characterized in that the disease is a cholestatic liver disease.