Novel aminopyridines and their use in cancer treatment

Abstract

The present invention provides substituted imidazo[4,5 - c]pyridine - 2 - The compounds of formula I inhibit DNA-dependent protein kinase (DNA) - It selectively inhibits the activity of PK, - It is useful in treating diseases in which inhibition of PK is beneficial. TIFF2023542548000315.tif3548

Description

Technical field

[0001] 1.Field of invention The present invention generally relates to substituted imidazo[4,5-c]pyridin-2-one compounds, prodrugs and pharmaceutically acceptable salts thereof. These compounds selectively inhibit the activity of DNA-dependent protein kinase (DNA-PK). The invention also relates to the use of these compounds, prodrugs, salts and solvates thereof to treat diseases modulated by DNA-PK, including cancer. The present invention also relates to pharmaceutical formulations of substituted imidazo[4,5-c]pyridin-2-one compounds. [Background technology]

[0002] 2. Background technology Cancer treatment still mainly uses cytotoxic agents, including therapies such as ionizing radiation and topoisomerase inhibitors, which produce DNA double-strand breaks (DSBs) as the main cytotoxic damage. All cells have a highly orchestrated DNA damage response (DDR) that involves repair of DNA damage. Two major repair mechanisms process DNA DSBs. Homologous recombination repair (HRR) uses sister chromatids to achieve high-fidelity repair during the S and G2 phases of the cell cycle, while non-homologous end joining (NHEJ) facilitates error-prone recombination of chromosomes during the entire cell cycle. invite These repair mechanisms create resistance to cytotoxic chemotherapy and radiotherapy. Conversely, loss of function of certain DDR pathways may sensitize cancer cells to certain cytotoxic agents through persistent DNA damage. Therapeutic targeting of DDR has been widely used to enhance the activity of conventional chemotherapy and overcome drug resistance.

[0003] Inactivation of components of the NHEJ pathway results in a highly radiosensitive phenotype, making NHEJ the primary repair pathway for radiation-induced DSBs. At the heart of NHEJ is the DNA-dependent protein kinase (DNA-PK) complex. It contains the proteins Ku70 and Ku80, which join the free DNA ends of DSBs and recruit the DNA-PK catalytic subunit (DNA-PKcs). The resulting complex autophosphorylates DNA-PKcs (Ser2056) and multiple other targets, resulting in DNA isolation and activation of Artemis, the XRCC4 complex, a specialized DNA polymerase and DNA ligase 4. Mobilize and reattach the rupture. Loss of DNA-PK function increases susceptibility to DSBs, and DNA-PK has been identified as a reliable drug target in DDR.

[0004] However, the selectivity of DNA-PK over other protein kinases has been an issue. DNA-PKcs, ataxia telangiectasia mutated (ATM), ATM-related (ATR) and mammalian target of rapamycin (mTOR), is a member of the PI3K-related kinase (PIKK) family. These are homologous to Pi3K enzymes, but are proteins (Ser / Thr) rather than lipid kinases. To be clinically useful, novel DNA-PK inhibitors must demonstrate at least some selectivity for DNA-PK compared to PI3K isoforms and other PIKK family members. There must be.

[0005] DNA-PK also has functions outside of its typical role in DSB repair. It has been reported to act on glucose deprivation, hypoxic tolerance, myogenic differentiation, endothelial cell function, vascular smooth muscle proliferation, neuroprotection, mitosis, telomere protection, inflammation, and regulation of immune responses. Therefore, normal tissue toxicity of DNA-PK inhibitors is not unexpected.

[0006] The combination of DDR inhibitors and DNA-damaging chemotherapy usually suffers from enhanced tissue toxicity, necessitating a reduction in the chemotherapy dose and impairing treatment efficacy. This suggests that the combination of DNA-PK inhibition and radiotherapy is a promising opportunity. Concerns about enhanced normal tissue toxicity in the radiation field have been countered to some extent by the advent of advanced conformal radiation therapy techniques such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), and stereotactic radiation therapy (SBRT). There is.

[0007] Tumor-selective drug delivery to hypoxic regions within solid tumors has the potential to provide another layer of selectivity to minimize normal tissue toxicity. Hypoxia is a major component of the tumor microenvironment. It plays a dynamic role in determining tumor progression and treatment response. Hypoxia also decreased RAD51 and BRCA1, limiting HRR repair in hypoxic cells and increasing dependence on NHEJ. Hypoxic cells confer resistance to treatments, particularly radiotherapy, and targeting these cells provides clinical benefit. Hypoxia-activated prodrugs are activated by enzymatic reduction in hypoxic tissue, releasing active agent that can diffuse into adjacent tumor tissue (local bystander effect).

[0008] Therefore, targeting DDR has considerable potential for cancer therapy, but novel DNA-PK inhibitors and / or effective hypoxia-activated prodrugs are required to deliver these compounds to tumors. is necessary. One objective of the present invention is therefore to at least somehow meet such needs, or at least to provide the public with a useful option.

[0009] Reference is generally made herein to external sources, including patent specifications and other documents, to provide a context for describing features of the invention. Unless otherwise stated, citation to such sources in any jurisdiction shall be construed as an admission that such sources form part of the state of the art or known art in the field. should not be done. [Summary of the invention]

[0010] 3.Summary of the invention The present inventors unexpectedly discovered that certain imidazo[4,5-c]pyridin-2-one compounds have high selectivity for DNA-PK and exhibit activity as DNA-PK inhibitors in vivo. I found out. These compounds are therefore useful in the treatment of diseases that would benefit from inhibition of such enzymes, such as cancer. The present invention also relates to such novel nitroheteroaryl prodrugs that are active in vivo against radiation (hypoxia) tumor cells.

[0011] Accordingly, there is provided a compound of any of the following formulas I, II, III, IV, V, VI, VII or XII or a salt thereof.

[0012] In another aspect, the invention provides a compound of formula I, II, III, IV, V, VI, or VII, or a salt or solvate thereof, in one or more pharmaceutically acceptable excipients. A pharmaceutical composition comprising:

[0013] In another aspect, the present invention provides a compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically thereof, in which DNA-PK inhibition is beneficial to a subject in need thereof. A method for treating a disease is provided comprising administering to a subject a therapeutically effective amount of an acceptable salt or solvate.

[0014] In another aspect, the invention provides a compound of formula I, II, III, IV, V, VI or VII or its pharmaceutical composition in the manufacture of a medicament for the treatment of diseases in which inhibition of DNA-PK is beneficial. Use of acceptable salts or solvates is provided.

[0015] In another aspect, the invention provides a compound of formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable form thereof, for the treatment of diseases in which inhibition of DNA-PK is beneficial. Provide a salt or solvate.

[0016] In one embodiment, the disease in which inhibition of DNA-PK would be beneficial is cancer.

[0017] In another aspect, the invention provides a method for combining a peptide substrate with an effective amount of a compound of any of Formulas I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof. A method of inhibiting DNA-PK-mediated subphosphorylation of a peptide is provided.

[0018] In another aspect, the invention provides a method for treating tumor cells with an effective amount of a compound of any of Formulas I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof. A method of radiosensitizing a tumor cell is provided.

[0019] In another aspect, the invention provides methods for contacting a tumor with an effective amount of a compound of any of Formulas I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof. Provided are methods for inhibiting tumor growth, including inhibiting tumor growth.

[0020] In another aspect, the invention provides treatment with any compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, in combination with radiotherapy. Provided are methods for treating cancer comprising administering to a subject an effective amount of a compound of formula I, II, III, IV, V, VI, or VII or a pharmaceutically acceptable compound thereof. A salt or solvate of the drug may be administered simultaneously, alone, or sequentially with radiation therapy.

[0021] In one embodiment, the radiation therapy is selected from the group consisting of IMRT, FRT, SBRT, SABR, and IORT.

[0022] In one embodiment, the cancer is head and neck squamous cell carcinoma.

[0023] Although the invention is generally defined above, it will be understood by those skilled in the art that it is not limited thereto, and that the invention further includes the embodiments described in the embodiments below. [Brief explanation of the drawing]

[0024] 4. Brief description of the drawing The present invention will now be described with reference to the accompanying drawings.

Figure 1

Figure 2

[0025] 5.Form for carrying out the invention The details of the invention are set forth in the accompanying description below.

[0026] However, methods and materials similar or equivalent to those described herein may be Here, exemplary methods and Explain the materials. Other features, objects, and advantages of the invention will be apparent from the description and claims. In the specification and the appended claims, the singular encompasses the plural. However, this shall not apply unless the context explicitly provides otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. All patents and publications cited herein are incorporated by reference.

[0027] 5.1 Definition As used herein, the following words, phrases, and symbols shall have the meanings generally indicated below, unless the context of use indicates otherwise.

[0028] The term "comprising," as used herein, means "consisting at least in part." When interpreting each term "inclusive" in this specification and in each claim, features other than those appearing in the section or item heading may also be present. Related terms such as "comprise" and "comprises" shall be interpreted interchangeably.

[0029] As used herein, the term "and / or" means "and" or "or" or both.

[0030] When the term "optionally" is used, the intent is the possibility that the subsequent feature may or may not occur. Thus, use of the term "optionally" includes instances where the feature is present as well as instances where the feature is not present. For example, a group "optionally substituted with one hydroxy" includes groups with or without a hydroxy substituent.

[0031] As used herein, the term "substituted" means that one or more hydrogens on a specified group are means substituted with the specified substituent. Combinations of substituents include only stabilized compounds and stabilized synthetic intermediates. As used herein, the term "stabilized" means that the relevant compound or intermediate is sufficiently robust to be isolated and as a synthetic intermediate or agent with potential therapeutic utility. It means that it has the usefulness of If a group is not described as "substituted" or "optionally substituted," the group is considered unsubstituted (i.e., the hydrogens of the particular group are not substituted).

[0032] The term "therapeutically effective amount" means an amount of a compound of the invention effective to provide "therapy" or "treat" a disease or disorder in a subject.

[0033] As used herein, the terms "therapy" and "treatment" refer to the treatment for the complete or partial alleviation of one, some or all of the symptoms, or for the potential It means to treat a disease in order to correct or compensate for its condition. Unless otherwise specified, the terms "therapy" and "treatment" also include "prophylaxis." The terms "therapeutic" and "therapeutically" should be interpreted appropriately. Similarly, the term "treatment" can also be interpreted as "applied therapy."

[0034] The term "prevention" includes primary prevention to prevent the onset of a disease, as well as primary prevention where the disease has already developed and the subject is temporarily or permanently protected from exacerbation of the disease or the onset of new symptoms associated with the disease. Includes protected secondary prevention.

[0035] The term "subject" as used herein in connection with a therapeutic method refers to a warm-blooded animal to whom the therapy is applied. Examples of warm-blooded animals include, but are not limited to, primates, domestic animals (eg, sheep, cows, pigs, goats, horses), and companion animals (eg, cats, dogs). In one embodiment, the warm-blooded animal is a human.

[0036] Asymmetric centers may be present in the compounds described herein. Asymmetric centers can be designated as (R) or (S) depending on the configuration of the substituent in three-dimensional space at the chiral carbon atom. All stereochemical forms of a compound, including diastereomeric, enantiomeric, and epimeric forms, as well as mixtures thereof, including d- and l-isomers, and enantiomerically enriched and diastereomerically enriched mixtures of stereochemically isomers. Isomeric forms are within the scope of this invention.

[0037] Individual enantiomers can be prepared synthetically from commercially available enantiomerically pure starting materials, or by preparing enantiomeric mixtures and resolving the mixtures into the individual enantiomers. Methods of resolution include conversion of an enantiomeric mixture into a diastereomeric mixture and isolation of the diastereomers, for example by recrystallization or chromatography, and any other suitable methods known in the art. Starting materials of defined stereochemistry are commercially available or prepared and can be resolved, if necessary, by techniques well known in the art.

[0038] The compounds described herein can also exist as conformational or geometric isomers, including cis, trans, syn, anti, entgegen (E) and zusammen (Z) isomers. All these isomers and any mixtures thereof are within the scope of this invention.

[0039] Tautomers of the compounds or mixtures thereof are also within the scope of the invention. As those skilled in the art will appreciate, various functional groups and other structures can exhibit tautomerism. Examples include, but are not limited to, ketones / enols, imines / enamines, thione / enethiol tautomers.

[0040] The compounds described herein can also exist as isotopologues and isotopomers in which one or more atoms in the compound are replaced with a different isotope. Suitable isotopes include, for example: 1 H, 2 H (D), 3 H (T), 12 C, 13 C, 14 C, 16 O, and 18 Contains O. Methods of incorporating such isotopes into the compounds described herein will be apparent to those skilled in the art, and isotopologues and isotopomers of the compounds described herein are also within the scope of the invention.

[0041] Also included within the scope of this invention are pharmaceutically acceptable salts of the compounds described herein. These salts include acid addition salts, base addition salts, and basic nitrogen group-containing quaternary salts. Acid addition salts can be prepared by reacting the free base form of the compound with an inorganic or organic acid. Examples of inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like. Examples of organic acids are acetic acid, trifluoroacetic acid, propionic acid, succinic acid, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, stearic acid. Acids include, but are not limited to, salicylic acid, methanesulfonic acid, benzenesulfonic acid, isethionic acid, sulfonic acid, adipic acid, butyric acid, pivalic acid, and the like. Base addition salts can be prepared by reacting the free acid form of the compound with an inorganic or organic base. Examples of inorganic base addition salts include alkali metal salts, alkaline earth metal salts, and other physiologically acceptable metal salts such as aluminum, calcium, lithium, magnesium, potassium, sodium or zinc salts. Examples of organic base addition salts include amine salts such as trimethylamine, diethylamine, ethanolamine, diethanolamine, ethylenediamine salts. Quaternary salts of basic nitrogen-containing groups in compounds include, for example, alkyl halides such as methyl, ethyl, propyl, butyl chlorides, bromides, iodides, dimethyl, diethyl, dibutyl, diamyl sulfates. It can be produced by reacting with a dialkyl sulfate such as.

[0042] The term "pharmaceutically acceptable" is used to identify a particular article (e.g., a salt, dosage form, diluent, or carrier) that is suitable for administration to a subject, particularly a human subject. It is. A list of examples of pharmaceutically acceptable salts is found in H. and book of Pharmaceutical Salts: Properties, Selection and Use, P. H. Stahl and C. G. Wermuth, editors, Weinheim / Zurich: Wiley-VCH / VHCA, 2002. There is.

[0043] Suitable pharmaceutically acceptable salts of compounds of formula (I) are, for example, acid addition salts. Acid addition salts of compounds of formula (I) can be formed by contacting the compound with a suitable inorganic or organic acid under conditions known to those skilled in the art. Acid addition salts can be formed using, for example, inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid. Acid addition salts include trifluoroacetic acid, citric acid, maleic acid, oxalic acid, acetic acid, formic acid, benzoic acid, fumaric acid, succinic acid, tartaric acid, lactic acid, pyruvic acid, mesylic acid, benzenesulfonic acid and p-toluenesulfonic acid. It can also be formed using an organic acid selected from the group consisting of:

[0044] The compounds described herein may form or exist as solvates in various solvents. When the solvent is water, the solvate can be referred to as a hydrate, such as a monohydrate, dihydrate, trihydrate. All dissolved and undissolved forms of the compounds described in this section are within the scope of the invention. Common chemical terms used herein have their usual meanings. Standard abbreviations for chemical groups are known to those skilled in the art, for example Me=methyl, Et=ethyl, iPr=isopropyl, Bu=butyl, t-Bu=t-butyl, Ph=phenyl, Bn=benzyl, Ac= Acetyl, Boc=t-butoxycarbonyl, Fmoc=9-fluorenylmethoxycarbonyl, Tf=triflate, OMOM=methoxymethyl ether, OMEM=methoxyethoxymethyl ether, OTBDMS=t-butyldimethylsilyl ether, DPPA=diphenylphosphoryl Azide, NBS=N-bromosuccinimide, NIS=N-iodosuccinimide, OPMB=4-methoxybenzyl ether, EDCI=1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, HOBt=hydroxybenzotriazole, OSEM=[ 2-(trimethylsilyl))ethoxy]methyl ether, Alloc=allyloxycarbonyl, Cbz=benzyloxycarbonyl, Teoc=(2-(trimethylsilyl)ethoxycarbonyl, TEMPO=2,2,6,6-tetramethyl-1-piperidinoxy , Troc=2,2,2-trichloroethylcarbonyl, etc.

[0045] As used herein, the term "halo," "halide," or "halogen group" refers to a fluorine, chlorine, bromine, or iodine group.

[0046] The term "amino" as used herein refers to -NH 2 means.

[0047] As used herein, the term "alkyl" refers to a saturated straight-chain or branched acyclic hydrocarbon group, e.g. (C 1 -C 20 )alkyl, (C 1 -C 8 )alkyl, and (C 1 -C 6 ) called alkyl. Exemplary alkyls are methyl, ethyl, 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-methyl-2-pentyl, 3-methyl- 2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, butyl, isobutyl, t-butyl, pentyl, Including, but not limited to, isopentyl, neopentyl, hexyl, heptyl, heptyl, octyl, and the like.

[0048] As used herein, the term "alkenyl" refers to an unsaturated straight chain or branched acyclic hydrocarbon group having at least one carbon-carbon double bond, such as 2-20, 2-8 or 2-6 (C 2 -C 20 )alkenyl, (C 2 -C 8 ) alkenyl and (C 2 -C 6 ) called alkenyl. Exemplary alkenyls include vinyl, allyl, butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, hexadienyl, 2-ethylhexenyl, 2-propyl-2-butenyl, and 4-(2-methyl-3-butenyl)-pentenyl. including but not limited to.

[0049] The term "cycloalkyl" as used herein refers to a saturated hydrocarbon cyclic group. Prefix “C” x ~C y '' (x and y are integers) when used in combination with the term ``cycloalkyl'' means the number of ring carbon atoms in the cycloalkyl. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexanyl, and bridged and caged saturated ring groups such as adamantane.

[0050] The term "heterocycloalkyl" refers to a single aliphatic ring containing at least 2 carbon atoms in addition to 1 to 3 heteroatoms independently selected from oxygen, sulfur, and nitrogen; means a combination containing at least one. Prefix “C” x ~C y ” (x and y are integers) when used in combination with the term “heterocycloalkyl” means the number of ring carbon atoms in the heterocycloalkyl. Suitable heterocycloalkyls include, for example, 2-pyrrolinyl, 2,4-imidazolidinyl, 2,3-pyrazolidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 2,5-piperidinyl (in order of priority). (numbered starting from connection position 1). Morpholinyl is also contemplated to include 2-morpholinyl, 3-morpholinyl (oxygen having priority 1). Substituted heterocycloalkyl is partially substituted by one or more oxo, such as piperidinyl N-oxide, morpholinyl N-oxide, 1-oxo-l-thiomorpholinyl, and 1,1-dioxo-1-thiomorpholinyl. Further including ring systems.

[0051] The term "aryl" as used herein refers to a cyclic aromatic hydrocarbon group that does not contain cyclic heteroatoms. Aryl includes monocyclic and bicyclic ring systems. Examples of aryl include, but are not limited to, phenyl, azulenyl, heptenyl, indenyl, indenyl, pentenyl and naphthyl. In some embodiments, the aryl has 6-20, 6-14, 6-12, or 6-10 carbon atoms in the ring. In some embodiments, aryl is phenyl or naphthyl. Aryl includes aromatic carbocyclic fused ring systems. Examples include, but are not limited to, indanyl and tetrahydronaphylyl. Prefix “C” x ~C y ” (where x and y are both integers) when used in combination with the term “aryl” means the number of ring carbon atoms in the aryl. In some embodiments, an "aryl" may be substituted with one or more of any substituents described herein.

[0052] The term "heteroaryl" as used herein means an aromatic ring system containing five or more ring atoms, one or more of which is a heteroatom. In some embodiments, the heteroatom is nitrogen, oxygen or sulfur. Heteroaryl is a variety of heterocyclic groups having an aromatic electronic structure. In some embodiments, heteroaryl includes monocyclic, bicyclic, and tricyclic rings having 5-20, 5-16, 5-14, 5-12, 5-10, 5-8, or 5-6 ring atoms. Contains ring systems. Heteroaryls include pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, benzothiophenyl, furanyl, benzofuranyl, indolyl, azaindolyl (pyrrolopyridinyl), indazolyl, benzimidazolyl, pyrazinyl. Includes zolopyridinyl, triazolopyridinyl, benzotriazolyl, benzoxazolyl, benzothiazolyl, imidazopyridinyl, imidazyl, guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl, Not limited to these. Heteroaryl includes fused ring systems in which all rings are aromatic, such as indolyl, and fused ring systems in which only one ring is aromatic, such as 2,3-dihydroindolyl. The prefix "x-y member" (x and y are integers) when used in combination with the term "heteroaryl" refers to the number of ring atoms in the heteroaryl. In some embodiments, a "heteroaryl" may be substituted with one or more of any substituents described herein.

[0053] References to numerical ranges (e.g., 1 to 10) disclosed herein refer to all rational numbers within this range (e.g., 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7). , 8, 9, and 10) and any rational number range within this range (e.g., 2 to 8, 1.5 to 5.5, and 3.1 to 4.7); All subranges of are expressly disclosed herein. These are only examples of specific intent, and all possible numerical combinations between the lowest and highest recited values ​​shall be deemed to be expressly set forth herein in the same manner. Should be.

[0054] 5.2 DNA-PK inhibitor compounds of the invention The present invention relates to imidazo[4,5-c]pyridin-2-one compounds that inhibit DNA-PK, and selected prodrug forms of these compounds.

[0055] In a first aspect, the invention provides a compound of formula I or a salt thereof. [ka] (here, X is selected from the group consisting of (a), (b), and (c) below, (a) -H; (b) -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 , -NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 , -NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 ,-Ph, -(C 3 -C 7 )cycloalkylamino, imidazolyl, piperazinyl, -(C 1 -C 6 )-alkylpiperazinyl and morpholinyl optionally substituted with one or more groups independently selected from 1- C 6 )alkyl; (c) -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 , -NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 , -NR 1 C(O)NHR 1 ,-NRC(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 , -SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 ,-Ph, -(C 3 -C 7 )cycloalkylamino, imidazolyl, piperazinyl, -(C 1 -C 6 )-alkylpiperazinyl and morpholinyl may be optionally substituted with one or more groups independently selected from (C 2- C 6 ) alkenyl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 , -NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 Ha-(C 1- C 6 ) alkyl, -Ph is -(C 1- C6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 optionally substituted with one or more groups independently selected from R 2 Ha-(C 1- C 6 ) alkyl, Y is selected from the group consisting of (a) to (f) below, (a) -OH, -halo, -OR 1 , -OC(O)H, -C(O)R 1 , -OC(O)NH 2 , -OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 , -SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 ,-Ph; -OH, -OR 1 ,-NH 2 ,-NHR 1 or -NR 1 R 1 -(C 3 -C 7 )cycloalkyl; and contains one oxygen atom or one nitrogen atom on the ring, -OH, -OR 1 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , or -(C 1- C 6 ) may be optionally substituted with alkyl-(C 3 -C 7 )heterocycloalkyl optionally substituted with one or more groups independently selected from -(C 1- C 6 )alkyl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 Ha-(C 1- C 6 ) alkyl, -Ph is -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 , -SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 optionally substituted with one or more groups independently selected from R 2 Ha-(C 1- C 6 ) alkyl, (b) -OH, -halo, -OR 1 , -OC(O)H, -C(O)R 1 , -OC(O)NH 2 , -OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 , -SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 ,-Ph; -OH, -OR 1 ,-NH 2 ,-NHR 1 or -NR 1 R 1 -(C 3 -C 7 )cycloalkyl; and contains one oxygen atom or one nitrogen atom on the ring, -OH, -OR 1 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , or -(C 1- C 6 ) may be substituted with alkyl-(C 3 -C 7 )heterocycloalkyl optionally substituted with one or more groups independently selected from -(C 2- C 6 ) alkenyl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 Ha-(C 1- C 6 ) alkyl, -Ph is -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 , -SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 optionally substituted with one or more groups independently selected from R 2 Ha-(C 1- C 6 ) alkyl, (c)-R 1 , -OH, -halo, -OR 1 , -OC(O)H,OC(O)R 1 , -OC(O)NH 2 , -OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 , -SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 ,-CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,as well as -CONR 1 S.O. 2 R 1 -(C 3- C 7 )cycloalkyl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 ,- CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 independently selected from -(C1-C6)alkyl optionally substituted with R 2 Ha-(C 1- C 6 ) alkyl, (D)-R 1 , -OH, -halo, -OR 1 , -OC(O)H, -C(O)R 1 , -OC(O)NH 2 , -OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 , -SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 ,-CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 , and -CONR 1 S.O. 2 R 1 -(C 3- C 7 )heterocycloalkyl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 ,- CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 independently selected from -(C1-C6)alkyl optionally substituted with R 2 Ha-(C 1- C 6 ) alkyl, (e) -R 1 , -OH, -halo, -OR 1 , -OC(O)H,OC(O)R 1 , -OC(O)NH 2 , -OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 , -NHC(O)NR 1 R 1 , -NR 1 C(O)NH 2 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NH 2 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H, -CONHSO 2 R 1 and-CONR 1 S.O. 2 R 1 -(C 4- C 8 )aryl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -O 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 Ha-(C 1- C 6 ) alkyl, (F) -R 1 , -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 , -NRC(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 , -CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 , and -CONR 1 S.O. 2 R 1 -(C 5- C 12 )heteroaryl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 Ha-(C 1- C 6 ) alkyl, Z is selected from the group consisting of (a) and (b) below, (A) -R 1 , -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 , -NR 1 C(O)NHR 1 ,-NR 1 C(O)NR1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 , -SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 , morpholinyl, piperazinyl, pyridinyl and pyrimidinyl, -(C 4- C 8 )aryl; Each R 1 is -(C 1- C 6 )alkyl and -(C 4 -C 8 )aryl, each of these groups being -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 ,-SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 may be arbitrarily substituted with R 2 Ha-(C 1- C 6 ) alkyl, Each of morpholinyl, piperazinyl, pyridinyl, and pyrimidinyl is -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 , -NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,C.H. 2 F, -CN, -CO 2 H, -CO 2 R 2 ,-CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 optionally substituted with one or more groups independently selected from R 2 Ha-(C 1- C 6 ) alkyl, (b) -R 1 , -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 , -NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 , -SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 -(C 5- C 12 )heteroaryl; Each R 1 Ha-(C 1- C 6 )alkyl and -(C 4 -C 8 )aryl, each of these groups being -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 ,-SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 may be arbitrarily substituted with R 2 Ha-(C 1- C 6 ) alkyl, Each of morpholinyl and piperazinyl is -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 ,-SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 optionally substituted with one or more groups independently selected from R 2 Ha-(C 1- C 6 ) is alkyl. ) In one embodiment, X is (b) below; (b) -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 , -NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 ,-Ph, -(C 3 -C 7 )cycloalkylamino, imidazolyl, piperazinyl, -(C 1 -C 6 )-alkylpiperazinyl and morpholinyl optionally substituted with one or more groups independently selected from 1- C 6 )alkyl; Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 Ha-(C 1- C 6 ) alkyl, -Ph is -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 , -SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and b-C(O)NR 2 R 2 optionally substituted with one or more groups independently selected from R 2 Ha-(C 1- C 6 ) is alkyl.

[0056] In one embodiment, X is -(C 1- C 6 ) is alkyl. In one embodiment, X is Me.

[0057] In one embodiment, X is OH or NH 2 -(C 1-6 ) alkylalkyl.

[0058] In one embodiment, Y is selected from the group consisting of (c), (d) and (e) above.

[0059] In one embodiment, Y is -(C 3- C 7 )cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, cyclohexanyl, pyrrolidinyl and phenyl, each of which groups -R 1 , -OH, -halo, -OR 1 , -OC(O)H, -C(O)R 1 , -OC(O)NH 2 , -OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 , -SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 ,-CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 and-CONR 1 S.O. 2 R 1 optionally substituted with one or more groups independently selected from Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 ,- CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 independently selected from -(C1-C6)alkyl optionally substituted with R 2 Ha-(C 1- C 6 ) alkyl, In one embodiment, Y is -(C 3- C 7)cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, methoxycyclohexanyl, hydroxycyclohexanyl, aminocyclohexanyl, N-methylaminocyclohexanyl, N,N-dimethylcyclohexanyl, pyrrolidinyl, N-methyl selected from the group consisting of pyrrolidinyl, piperidinyl, N-methylpiperidinyl, furanyl, pyrrolyl, pyridinyl, hydroxyphenyl, and methoxyphenyl.

[0060] In one embodiment, Y is selected from the group consisting of tetrahydropyranyl, aminocyclohexanyl, hydroxycyclohexanyl, methoxycyclohexanyl and piperidinyl.

[0061] In one embodiment, Y is 4-tetrahydropyranyl or 4-piperidinyl.

[0062] In one embodiment, Y is selected from the group consisting of furanyl, pyrrolyl and pyridinyl.

[0063] In one embodiment, Y is selected from the group consisting of 4-methoxycyclohexanyl, 4-hydroxycyclohexanyl or 4-aminocyclohexanyl.

[0064] In one embodiment, Y is 4-hydroxyphenyl or 4-methoxyphenyl.

[0065] In one embodiment, Z is furanyl, thiophenyl, pyrrolyl, pyridinyl, imidazolyl, thiazolyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, purinyl, benzodioxolyl, quinoxalinyl, benzothiazinyl, triazolopyridinyl, -(C 5- C 12 )heteroaryl, and each of these groups represents -R 1 , -OH, -halo, -OR 1 , -OC(O)H, -C(O)R 1 , -OC(O)NH 2 , -OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 , -NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 , -SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 ,-CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 and-CONR 1 S.O. 2 R 1 optionally substituted with one or more groups independently selected from Each R 1 Ha-(C 1- C 6 )alkyl and -(C 4- C 8 )aryl, each of these groups being -halo, -OH, -OR 2 ,-NO 2 , -NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 , -SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 ,- CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 may be arbitrarily substituted with R 2 Ha-(C 1- C 6 ) alkyl, In one embodiment, Z is pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, purinyl, benzodioxolyl, quinoxalinyl, benzothiazinyl, triazolopyridinyl, benzothiazolyl, benzoxazolyl, benzodioxolyl and selected from the group consisting of imidazopyridinyl -(C 5- C 12 )heteroaryl, each group is -(C 1- C 6 )aryl, -OH, -halo, -OR 1 , -OC(O)H, -C(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 , -NH 2 ,-NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 , -NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 , -NHC(O)NR 1 R 1 ,-NRC(O)NHR 1 ,-NRC(O)NR 1 R 1 ,-SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F,-CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 ,-C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 , and -CONR 1 S.O. 2 R 1 and Each R 1 is -(C 1- C 6 )alkyl and -(C 4- C 8 )aryl, each of these groups being halo, -OH, -OR 2 ,-NO 2 , -NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 , -C(O)NR 2 R 2 may be arbitrarily substituted with R2 Ha-(C 1- C 6 ) is alkyl.

[0066] In one embodiment, Z is (C 1- C 6 )alkyl, preferably Me substituted -(C 5- C 12 ) is a heteroaryl.

[0067] In one embodiment, Z is (C 1- C 6 )alkyl, preferably Me substituted -(C 4- C 8 ) is an aryl.

[0068] In one embodiment, Z is R 1 , -OH, -OR 1 , -halo, -NO 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 ,-SO 2 R 1 and phenyl optionally substituted with one or more of -Bn, and -R 1 is(C 1- C 6 ) alkyl, preferably Me.

[0069] In one embodiment, Z is -OMe, -Cl, and It is phenyl substituted with either -OH.

[0070] In one embodiment, Z is -SO at the 5th position 2 R 1 and NO 2 is phenyl substituted with either -R 1 is(C 1- C 6 ) alkyl, preferably Me.

[0071] In one embodiment, Z is the group consisting of 4-methoxy-2-methylphenyl, 4-chloro-2-methylphenyl, 5-(methylsulfonyl)-2-methylphenyl, and 4-hydroxy-2-methylphenyl. selected from.

[0072] In one embodiment, Z is 4-methoxy-2-methylphenyl.

[0073] In a second aspect, the invention provides a compound of formula II or a salt thereof. [ka] Here, X and Y are defined as in formula I, A 1、 A 2 and A 3 is independently selected from CH or N, B 1 -OH, -OR 1 , halo, -NO 2 ,-NH 2 , N.H.R. 1 ,-SO 2 R 1 and -OBn, Each R 1 is halo, -OH, -OR 2 ,-NO 2 ,-NH 2 , -NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl, R 2 Ha-(C 1- C 6 ) is alkyl.

[0074] In one embodiment, X is Me.

[0075] In one embodiment, Y is -(C 3- C 7 )cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, methoxycyclohexanyl, hydroxycyclohexanyl, aminocyclohexanyl, N-methylaminocyclohexanyl, N,N-dimethylcyclohexanyl, pyrrolidinyl, N-methyl selected from the group consisting of pyrrolidinyl, piperidinyl, N-methylpiperidinyl, furanyl, pyrrolyl, pyridinyl, hydroxyphenyl, and methoxyphenyl.

[0076] In one embodiment, Y is selected from the group consisting of tetrahydropyranyl, aminocyclohexanyl, hydroxycyclohexanyl, methoxycyclohexanyl and piperidinyl.

[0077] In one embodiment, Y is 4-tetrahydropyranyl or 4-piperidinyl.

[0078] In one embodiment, Y is selected from the group consisting of furanyl, pyrrolyl and pyridinyl.

[0079] In one embodiment, Y is selected from the group consisting of 4-methoxycyclohexanyl, 4-hydroxycyclohexanyl or 4-aminocyclohexanyl.

[0080] In one embodiment, Y is 4-hydroxyphenyl or 4-methoxyphenyl.

[0081] In one embodiment, A1 is N, A 2 and A 3 is C, B 1 is OMe.

[0082] In a third aspect, the invention provides a compound of formula III or a salt thereof. [ka] Here, X and Y are defined as in formula I, A 1 is N or C.

[0083] D is selected from N, O, S, R 3 is H, -(C 1- C 6 )alkyl, -CO 2 R 1 ,-CONHR 1 and CONHR 1 R 1 selected from the group consisting of R 1 Ha-(C 1- C 6 ) is alkyl.

[0084] In one embodiment, X is Me.

[0085] In one embodiment, Y is -(C 3- C 7 )cycloaryl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, methoxycyclohexanyl, hydroxycyclohexanyl, aminocyclohexanyl, N-methylaminocyclohexanyl, N,N-dimethylcyclohexanyl, pyrrolidinyl, N-methyl selected from the group consisting of pyrrolidinyl, piperidinyl, N-methylpiperidinyl, furanyl, pyrrolyl, pyridinyl, hydroxyphenyl and methoxyphenyl.

[0086] In one embodiment, Y is selected from the group consisting of tetrahydropyranyl, aminocyclohexanyl, hydroxycyclohexanyl, methoxycyclohexanyl and piperidinyl.

[0087] In one embodiment, Y is 4-tetrahydropyranyl or 4-piperidinyl.

[0088] In one embodiment, Y is selected from the group consisting of furanyl, pyrrolyl and pyridinyl.

[0089] In one embodiment, Y is selected from the group consisting of 4-methoxycyclohexanyl, 4-hydroxycyclohexanyl or 4-aminocyclohexanyl.

[0090] In one embodiment, Y is 4-hydroxyphenyl or 4-methoxyphenyl.

[0091] In one embodiment, R 3 is H, Me, OMe or CO 2 It is Me.

[0092] In one embodiment, A 1 is N, D is CH, and R 3 is H.

[0093] In one embodiment, A 1 is N, D is N, and R 3 is H.

[0094] In one embodiment, A 1 is N, D is CH, and R 3 is CO 2 It is Me.

[0095] In a fourth aspect, the invention provides compounds of formula IV. [ka] Here, X and Y are defined as in formula I, B 2 and D are independently selected from N, O and S, [ka] Represents a single or double bond, [ka] is a single bond unless D is N, R 3 is H, -(C 1- C 6 )alkyl, -CO 2 R 1 ,-CONHR 1 and CONHR 1 R 1 selected from the group consisting of R 1 Ha-(C 1- C 6 ) is alkyl.

[0096] In one embodiment, X is Me.

[0097] In one embodiment, Y is -(C 3- C 7 )cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, methoxycyclohexanyl, hydroxycyclohexanyl, aminocyclohexanyl, N-methylaminocyclohexanyl, N,N-dimethylcyclohexanyl, pyrrolidinyl, N-methyl selected from the group consisting of pyrrolidinyl, piperidinyl, N-methylpiperidinyl, furanyl, pyrrolyl, pyridinyl, hydroxyphenyl, and methoxyphenyl.

[0098] In one embodiment, Y is selected from the group consisting of tetrahydropyranyl, aminocyclohexanyl, hydroxycyclohexanyl, methoxycyclohexanyl and piperidinyl.

[0099] In one embodiment, Y is 4-tetrahydropyranyl or 4-piperidinyl.

[0100] In one embodiment, Y is selected from the group consisting of furanyl, pyrrolyl and pyridinyl.

[0101] In one embodiment, Y is selected from the group consisting of 4-methoxycyclohexanyl, 4-hydroxycyclohexanyl or 4-aminocyclohexanyl.

[0102] In one embodiment, Y is 4-hydroxyphenyl or 4-methoxyphenyl.

[0103] In one embodiment, R 3 is H, Me or OMe.

[0104] In one embodiment, B 2 is N, D is O or S, and R 3 is Me.

[0105] In one embodiment, B 2 is N and D is O.

[0106] In addition to the above-mentioned DNA-PK inhibitors, the present invention also provides a prodrug compound containing the DNA-PK inhibitor of the present invention and an aromatic nitroheterocycle or nitrocarbocycle that breaks upon reduction (reducible prodrug trigger ) and includes.

[0107] Accordingly, in a fifth aspect, the invention provides a compound of formula V or a salt thereof. [ka] where X, Y, and Z are defined in formula I, Pro is [ka] where * represents the point of connection with the N atom of formula V.

[0108] R 11 is -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 , -NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H,-CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 ,-Ph, -(C 3 -C 7 )cycloalkylamino, imidazolyl, piperazinyl, -(C 1 -C 6 )-Alkylpiperazinyl and morpholinyl optionally substituted with -(C 1- C 6 ) alkyl, Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 , -CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 Ha-(C 1- C 6 ) alkyl, -Ph is -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 , -NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 , -C(O)NR 2 R 2may be optionally substituted with one or more of R 2 Ha-(C 1- C 6 ) alkyl, R 12 and R 13 are independently selected from the group consisting of -H, -Me and -Et.

[0109] In one embodiment, X is Me.

[0110] In one embodiment, Y is -(C 3- C 7 )cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, methoxycyclohexanyl, hydroxycyclohexanyl, aminocyclohexanyl, N-methylaminocyclohexanyl, N,N-dimethylcyclohexanyl, pyrrolidinyl, N-methyl selected from the group consisting of pyrrolidinyl, piperidinyl, N-methylpiperidinyl, furanyl, pyrrolyl, pyridinyl, hydroxyphenyl, and methoxyphenyl.

[0111] In one embodiment, Y is selected from the group consisting of tetrahydropyranyl, aminocyclohexanyl, hydroxycyclohexanyl, methoxycyclohexanyl and piperidinyl.

[0112] In one embodiment, Y is 4-tetrahydropyranyl or 4-piperidinyl.

[0113] In one embodiment, Y is selected from the group consisting of furanyl, pyrrolyl and pyridinyl.

[0114] In one embodiment, Y is selected from the group consisting of 4-methoxycyclohexanyl, 4-hydroxycyclohexanyl or 4-aminocyclohexanyl.

[0115] In one embodiment, Y is 4-hydroxyphenyl or 4-methoxyphenyl.

[0116] In one embodiment, Z is (C 1- C 6 )alkyl, preferably Me substituted -(C 5- C 12 ) is a heteroaryl.

[0117] In one embodiment, Z is [ka] and A 1 is N or C, D is selected from the group consisting of N, O, S and R 3 is H, -(C 1- C 6 )alkyl, -CO 2 R 1 ,-CONHR 1 and CONHR 1 R 1 selected from the group consisting of R 1 Ha-(C 1- C 6 ) is alkyl.

[0118] In one embodiment, R 3 is H, Me, OMe or CO 2 It is Me.

[0119] In one embodiment, A 1 is N, D is CH, and R 3 is H.

[0120] In one embodiment, A 1 is N, D is N, and R 3 is H.

[0121] In one embodiment, A 1 is N, D is CH, and R 3 is CO 2 It is Me.

[0122] In one embodiment, Z is [ka] and B 2 and D are independently selected from the group consisting of N, O and S; [ka] represents a single bond or a double bond, [ka] is a single bond unless D is N, and R 3 is H, -(C 1- C 6 )alkyl, -CO 2 R 1 ,-CONHR 1 and CONHR 1 R 1 selected from the group consisting of R 1 Ha-(C 1- C 6 ) is alkyl.

[0123] In one embodiment, R 3 is H, Me or OMe.

[0124] In one embodiment, B 2 is N, D is O or S, and R 3 is Me.

[0125] In one embodiment, B 2 is N and D is O.

[0126] In one embodiment, Z is (C 1- C 6 )alkyl, preferably Me substituted -(C 4- C 8 ) is an aryl.

[0127] In one embodiment, Z is R 1 , -OH, -OR 1 , -halo, -NO 2 , -NH 2 ,-NHR 1 ,-NR 1 R 1 ,-SO 2 R 1 and phenyl optionally substituted with one or more of -Bn, and -R 1 is(C 1- C 6 ) alkyl, preferably Me.

[0128] In one embodiment, Z is -OMe, -Cl, and It is phenyl substituted with either -OH.

[0129] In one embodiment, Z is -SO at the 5th position 2 R 1 and NO 2 is phenyl substituted with either -R 1 is(C 1- C 6 ) alkyl, preferably Me.

[0130] In one embodiment, Z is the group consisting of 4-methoxy-2-methylphenyl, 4-chloro-2-methylphenyl, 5-(methylsulfonyl)-2-methylphenyl, and 4-hydroxy-2-methylphenyl. selected from.

[0131] In one embodiment, Z is 4-methoxy-2-methylphenyl.

[0132] In one embodiment, the Pro [ka] , where R 12 and R 13 is defined as above.

[0133] In one embodiment, Pro: [ka] selected from the group consisting of.

[0134] In one embodiment, X is Me, Y is tetrahydropyranyl, Z is 4-methoxy-2-methylphenyl, and Pro is [ka] It is.

[0135] In a sixth aspect, the invention provides a compound of formula VI or a salt thereof. [ka] Here, X and Y are defined as in formula I, E is -O-, -NHCO 2 -, -N(Me)CO 2 -, -COO-, -NH(C 1- C 6 )aryl, -O-(C 1 -C 6 )alkyl-N-dimethylamino-, -NH(C 1- C 6 )alkyl-N-dimethylamino-, -NHCO(C 1- C 6 )alkyl-N-dimethylamino- and -NHCOCH=CHCH 2selected from -N-dimethylamino-, Pro is [ka] and Here, * represents the connection point with E in formula VI, Each R 11 is -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 , -NH 2 , -NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F,-CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H, -CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 , -Ph, -(C 3 -C 7 )cycloalkylamino, imidazolyl, piperazinyl, -(C 1 -C 6 )-alkylpiperazinyl and morpholinyl-(C 1- C 6 ) alkyl, Each R 1 -halo, -OH, -OR 2 ,-NO 2 , -NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl independently selected from R 2 is-C 1 - 6 is alkyl, -Ph is -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 , -NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 and -C(O)NR 2 R 2 optionally substituted with one or more groups independently selected from R 2 Ha-(C 1- C 6 ) alkyl, R 12 and R 13 are independently selected from the group consisting of -H, -Me and -Et, and R 14 -H, -Me, -Et, -OMe, -CF 3 , -CN and ethynyl.

[0136] However, E is -O-(C 1 -C 6 )alkyl-N-dimethylamino-, -NH(C 1- C 6 )alkyl-N-dimethylamino-, -NHCO(C 1- C 6 )alkyl-N-dimethylamino- or -NHCOCH=CHCH 2 When selected from -N-dimethylamino-, Pro is [ka] It is.

[0137] In one embodiment, the Pro [ka] , where R 12 and R 13 is defined above and E is -O-.

[0138] In one embodiment, Pro: [ka] selected from the group consisting of, E is -O- or NHCO 2 .

[0139] In one embodiment, the Pro [ka] and R 14 is defined above and E is O-(C 1 -C 6 )alkyl-N-dimethylamino, preferably -OCH 2 CH 2 NMe 2 or -OCH 2 CH 2 CH 2 NMe 2 It is.

[0140] In one embodiment, X is Me.

[0141] In one embodiment, Y is -(C 3- C 7 )cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, methoxycyclohexanyl, hydroxycyclohexanyl, aminocyclohexanyl, N-methylaminocyclohexanyl, N,N-dimethylcyclohexanyl, pyrrolidinyl, N-methyl selected from the group consisting of pyrrolidinyl, piperidinyl, N-methylpiperidinyl, furanyl, pyrrolyl, pyridinyl, hydroxyphenyl, and methoxyphenyl.

[0142] In one embodiment, Y is selected from the group consisting of tetrahydropyranyl, aminocyclohexanyl, hydroxycyclohexanyl, methoxycyclohexanyl and piperidinyl.

[0143] In one embodiment, Y is 4-tetrahydropyranyl or 4-piperidinyl.

[0144] In one embodiment, Y is selected from the group consisting of furanyl, pyrrolyl and pyridinyl.

[0145] In one embodiment, Y is selected from the group consisting of 4-methoxycyclohexanyl, 4-hydroxycyclohexanyl or 4-aminocyclohexanyl.

[0146] In one embodiment, Y is 4-hydroxyphenyl or 4-methoxyphenyl.

[0147] In one embodiment, Pro: [ka] and E is O.

[0148] In one embodiment, X is Me, Y is tetrahydropyranyl, and Pro is [ka] It is.

[0149] In one embodiment, X is Me, Y is 4-methoxycyclohexanyl, and Pro is [ka] It is.

[0150] In one embodiment, X is Me, Y is 4-methoxyphenyl, and Pro is [ka] It is.

[0151] In a seventh aspect, the invention provides a compound of formula VII [ka] Here, X and Z are defined as in formula I, Here, J is CH 2 or does not exist; [ka] is a saturated ring or an unsaturated ring, B 3 is C or N, G is -O-, -NHCO 2 -, -N(Me)CO 2 -, -COO-, -NH(C 1- C 6 )aryl, -O-(C 1 -C 6 )alkyl-N-dimethylamino-, -NH(C 1- C 6 )alkyl-N-dimethylamino-, -NHCO(C 1 -C 6 )alkyl-N-dimethylamino, and -NHCOCH=CHCH 2 -N-dimethylamino; and Pro is [ka] and Here, * represents the connection point with G in formula VII, Each R 11 is -OH, -halo, -OR 1 , -OC(O)H, -OC(O)R 1 , -OC(O)NH 2 ,-OC(O)NHR 1 , -O(CO)NR 1 R 1 , -OP(O)(OH) 2 , -OP(O)(OR 1 ) 2 ,-NH 2 , -NHR 1 ,-NR 1 R 1 , -NHC(O)H, -NHC(O)R 1 ,-NRC(O)R 1 , -NHC(O)NH 2 , -NHC(O)NHR 1 ,-NR 1 C(O)NH 2 , -NHC(O)NR 1 R 1 ,-NR 1 C(O)NHR 1 ,-NR 1 C(O)NR 1 R 1 , -SH, -SR 1 , -S(O)H, -S(O)R 1 ,-SO 2 R 1 ,-SO 2 N.H. 2 ,-SO 2 NHR 1 ,-SO 2 NR 1 R 1 ,-CF 3 ,-CHF 2 ,-CH 2 F,-CN, -CO 2 H, -CO 2 R 1 , -CHO, -C(O)R 1 , -C(O)NH 2 , -C(O)NHR 1 , -C(O)NR 1 R 1 ,-CONHSO 2 H, -CONHSO 2 R 1 ,-CONR 1 S.O. 2 R 1 , -Ph, -(C 3 -C 7 )cycloalkylamino, imidazolyl, piperazinyl, -(C 1 -C 6 )-Alkylpiperazinyl and morpholinyl optionally substituted with -(C 1- C 6 ) alkyl, Each R 1 -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 , -SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 or -C(O)NR 2 R 2 -(C 1- C 6 ) alkyl, each R 2 -C 1 - 6 is alkyl, -Ph -(C 1- C 6 )alkyl, -halo, -OH, -OR 2 ,-NO 2 ,-NH 2 ,-NHR 2 ,-NR 2 R 2 , -SH, -SR 2 ,-SO 2 R 2 ,-SO 2 N.H. 2 ,-CF 3 ,-CHF 2 ,-CH 2 F, -CN, -CO 2 H, -CO 2 R 2 , -CHO, -C(O)R 2 , -C(O)NH 2 , -C(O)NHR 2 as well as -C(O)NR 2 R 2 each R 2 is-C 1 - 6 It is an alkyl.

[0152] R 12 and R 13 are independently selected from -H, -Me and -Et, R 14 -H, -Me, -Et, -OMe, -CF 3 , -CN and ethynyl.

[0153] However, G is -O-(C 1 -C 6 )alkyl-N-dimethylamino-, -NH(C 1- C 6 )alkyl-N-dimethylamino-, -NHCO(C 1- C 6 )alkyl-N-dimethylamino-, or -NHCOCH=CHCH 2 When selected from -N-dimethylamino, Pro is [ka] It is.

[0154] [ka] B if and only if is a saturated ring 3 is N, B 3 G is -COO- if and only if is N and B 3 G is -O- if and only if is C.

[0155] In one embodiment, Z is (C 1- C 6 )alkyl, preferably Me substituted -(C 5- C 12 ) is a heteroaryl.

[0156] In one embodiment, Z is (C 1- C 6 )alkyl, preferably Me substituted -(C 4- C 8 ) is an aryl.

[0157] In one embodiment, Z is R 1 , -OH, -OR 1 , -halo, -NO 2 ,-NH 2 ,-NHR 1 ,-NR 1 R 1 ,-SO 2 R 1 and phenyl optionally substituted with one or more of -Bn, and -R 1 is(C 1- C 6 ) alkyl, preferably Me.

[0158] In one embodiment, Z is -OMe, -Cl, and It is phenyl substituted with either -OH.

[0159] In one embodiment, Z is -SO at the 5th position 2 R 1 and NO 2 is phenyl substituted with either -R 1 is(C 1- C 6 ) alkyl, preferably Me.

[0160] In one embodiment, Z is the group consisting of 4-methoxy-2-methylphenyl, 4-chloro-2-methylphenyl, 5-(methylsulfonyl)-2-methylphenyl, and 4-hydroxy-2-methylphenyl. selected from.

[0161] In one embodiment, Z is 4-methoxy-2-methylphenyl.

[0162] In one embodiment, the Pro [ka] , where R 12 and R 13 is defined above and G is -NHCO 2 -is.

[0163] In one embodiment, the Pro [ka] and G is -NHCO 2 -.

[0164] In one embodiment, J is absent, the ring is saturated, and B 3 is N and G is CO 2 and Pro is [ka] It is.

[0165] In one embodiment, J is absent, the ring is saturated, and B 3 is CH and G is NHCO 2 and Pro is [ka] It is.

[0166] Prodrug compounds of Formulas V-VII include a DNA-PK inhibitor of the invention and a reducible "trigger". Reducible triggers are aromatic nitroheterocycles or nitrocarbocycles that undergo fragmentation upon reduction. Preferably, the nitroheterocycle or nitrocarbocycle unit is linked to the DNA-PK inhibitor effector via a carbamate linkage, ether linkage or quaternary ammonium linkage.

[0167] Prodrug compounds of the invention are reduced in vivo by enzymes, radiation-induced radicals and / or chemical reducing agents. Under reducing conditions, active DNA-PK inhibitor is released by fragmentation of the trigger, and the oxygen or nitrogen atom bound to the trigger becomes the remaining portion of the released DNA-PK inhibitor.

[0168] The prodrug compounds of the invention selectively release DNA-PK inhibitors in tumors, more specifically in hypoxic regions within tumors. One common feature of most tumors is that the tissue area of ​​the tumor has low oxygen levels (hypoxia). Related terms such as "hypoxia" and "hypoxia" refer to conditions in which the concentration of oxygen in tissues is significantly lower than the normal physiological concentration of oxygen in healthy, well-perfused tissues, especially oxygen This means that the partial pressure is approximately 1% (10,000 parts per million of oxygen; 7.6 mmHg) or less. The terms "anoxia" and "anoxic condition" refer to conditions of oxygen deficiency or near oxygen deficiency.

[0169] Under conditions of hypoxia or anoxia, endogenous one-electron enzymes such as cytochrome P450 oxidoreductase (POR) reduce nitro to nitro anion.

[0170] This process is illustrated in general formula 1 below for compounds of formula V.

[0171] [ka] The nitro radical anion functions as an oxygen sensor as it is reoxidized to the starting prodrug with the formation of superoxide.

[0172] Such one-electron reductase reduction effectively targets the release of DNA-PK inhibitors to hypoxic regions within the tumor. The presence of oxygen inhibits reduction in normally oxidized tissues.

[0173] While not wishing to be bound by theory, oxidized regions that limit the release of DNA-PK inhibitors into hypoxic tissues and subsequent diffusion of the inhibitor into tumors may be associated with endogenous enzyme-mediated tumor selectivity. It is considered to be the main basis of This targeting nature of releasing DNA-PK inhibitors to tumors is also advantageous in expanding the therapeutic opportunities of such inhibitors.

[0174] In general, the prodrugs of the present invention formed by the combination of a fragmentation reduction activation trigger and a DNA-PK inhibitor have been determined by the applicant to possess a number of surprising properties, making them particularly suitable as targeted anticancer agents. Ru. The most important of these functions is its targeting effect. Many reductive triggers are widely known.

[0175] However, it cannot be guaranteed that the combination of each trigger and a specific effector is effective, and each combination must be optimized empirically. We demonstrate that the specific triggers defined above bind specific DNA-PK inhibitors to inactivate the effectors, are stable and allow delivery of prodrugs to tumors. did. Prodrugs are also effectively fragmented to release cytotoxic effectors under hypoxic conditions and have therapeutic antitumor effects.

[0176] In an eighth aspect, the invention provides compounds of formula XII. [ka] Here, X, Y, and Z are defined by Formula I.

[0177] Anilinoimidazopyridinones, exemplified by compounds of formulas I, II, III and IV, are not found in compounds analogous to 2-anilino-7,9-dihydropurin-8-one described in formula XIII. provides an opportunity to prepare hypoxia-activated prodrugs of compounds of the present invention. Preparation of carbamate prodrugs of these DNA-PK inhibitors (e.g., 247, 248, 250, 251, 254-259) is facilitated by the very stable intermediate carbamoyl chloride (e.g., 249, Scheme 33). It is considered possible. Such stable intermediates offer advantages, including isolation and purification, allowing for improved synthesis conditions and rapid purification from starting materials prior to subsequent reactions and installation of the nitroaryl trigger. do. Repeating this procedure using the corresponding 2-anilino-7,9-dihydropurin-8-one core of formula XIII (such as AZD7648) yields no results, indicating that the carbamoyl chloride intermediate is unstable. Shown.

[0178] [ka] 5.3 DNA-PK inhibition by compounds of the invention 5.3.1 Inhibition of DNA-PKcs and related kinases Compounds of the invention are evaluated as inhibitors of DNA-PK-mediated phosphorylation of peptide substrates (Table 12). Compounds are also evaluated against the related PI3-K and PIKK members mTOR kinase. These compounds inhibit DNA-PK in the nM to μM range and exhibit selectivity for DNA-PK compared to PI-3K and mTOR.

[0179] 5.3.2 Comparative Inhibition of 397 Kinases and 20 Lipid Kinases The selectivity of certain embodiments of the invention is evaluated at a concentration of 1 μM against 397 kinases and 20 lipid kinases. Compounds 48 (Table 13, Figure 1) and 121 (Table 14, Figure 2) showed significant selectivity for DNA-PK compared to other kinases.

[0180] 5.3.3. Selectivity for DNA-PKcs compared to other PIKK kinases Other members of the phosphatidylinositol 3-kinase related kinase family (ATM, ATR, mTOR) and related phosphatidylinositol 3-kinase isoforms (PI3Kα, β, γ, δ), the selectivity of the compounds of the present invention for DNA-PK was confirmed in Table 15 and FIG. Examples of the invention demonstrate increased selectivity of DNA-PK for PIKK kinase compared to other known kinase inhibitors (AZD7648).

[0181] 5.3.4 Radiosensitizing Effect of Human Head and Neck Cancer Cells The ability of compounds of the invention to radiosensitize human tumor cells is evaluated using proliferation endpoints under aerobic conditions. Before treatment with 0 or 3 Gy of radiation, UT-SCC-54C cells are cultured with certain concentrations of compounds for 1 hour and incubated for an additional 24 hours. Wash out the drug and allow the cells to repopulate for 5 days before fixing and staining with sulforhodamine B. The compound of the present invention exhibits a concentration-dependent radiosensitizing effect on UT-SCC-54C cells, and has almost no cytotoxicity in the absence of radiation (Figure 3). Cytotoxicity is defined as the drug concentration required to inhibit culture regrowth by 50% during the assay: IC50 value. Radiosensitivity was defined as the drug concentration required to inhibit repopulation of the culture by 50% during the assay in combination with 3 Gy radiation: S50 value (Table 16). Examples of prodrugs of the compound (e.g., 234, 236, 238, 240, 246, 247, 248, 250, 251, 257, 258, and 259) do not exhibit differential growth inhibition and effective inactivation of the drug. prove.

[0182] 5.3.5. DNA-PKcs-dependent radiosensitization of cells HAP1 wild-type cell line and PRKDC (HAP1 / PRKDC - / - Example of the present invention is evaluated as a radiosensitizer in a growth inhibition test using a DNA-PK-ineffective HAP1 system having a CRISPR-induced shift mutation in ). As shown in Figure 4 and Table 18, compounds 48, 88, 121, 125, 126, 127, 129, 132, and 135 induced concentration-dependent radiosensitization of HAP1 cells, and compared to irradiation with radiation alone, , significantly inhibited repopulation of cultures after 3 Gy cobalt-60γ irradiation and had little effect on non-irradiated HAP1 cells. On the other hand, compounds 48, 88, 121, 125, 126, 127, 129, 132 and 135 did not show radiosensitization of the HAP 1 cell line, which abolished DNA-PK-dependent radiosensitization of HAP cells. . Additionally, prodrugs 135, 234, 236, and 248 can be used in HAP1 cells or PRKDCs. - / - In the presence of radiation in cells, no different growth inhibition is shown, indicating inactivation of this drug.

[0183] 5.3.6 Inhibits autophosphorylation of Ser2056 of DNA-PKcs in cells. Further evidence of the cellular mechanism of action of the compounds of the invention was confirmed by inhibiting the autophosphorylation of DNA-PKcs by Ser2056. Irradiation of UT-SCC-54C hypoxic cells with 10 Gy induced autophosphorylation of Ser 2056 on DNA-PKcs and compounds 48 and 88, and inhibition of Ser 2056 autophosphorylation under hypoxia Confirmed (Figure 5). Similarly, compounds 48 and 88 were shown to inhibit radiation-induced autophosphorylation of Ser2056 under hypoxic conditions (Figure 6). Prodrug 234 hardly inhibits the autophosphorylation of Ser 2056 under hypoxia, but when the experiment was performed under hypoxia, prodrug 234 was able to inhibit the phosphorylation of Ser 2056 (Figure 6). .

[0184] UT-SCC-54 C cells irradiated with 10 Gy under aerobic conditions induced autophosphorylation of Ser 2056 on DNA-PKcs and phosphorylation of Ser 1981 on ATM (Figure 7). Compounds 48, 121, 195, and the announced DNA-PK inhibitors M3814 and IC87361 demonstrated an inhibitory effect on Ser 2056 of DNA-PKcs, but no inhibitory effect on Ser 1981 of ATM was observed. On the other hand, the ATM inhibitor AZD1393 inhibits radiation-induced phosphorylation of Ser 1981 on ATM, but does not affect the autophosphorylation of Ser 2056 on DNA-PKcs. Prodrug 234 does not inhibit phosphorylation of either enzyme under aerobic conditions.

[0185] 5.3.7. Hypoxic selective metabolism of prodrugs releases DNA-PK inhibitors. UT-SCC-54C cells selectively metabolize prodrug 248 under anoxic conditions but not under aerobic conditions, confirming hypoxic selective release of DNA-PK inhibitor 121 (Figure 13).

[0186] 5.3.8 Radiosensitization of Human Head and Neck Cancer Cells When evaluated using clonogenic survival endpoints, the compounds of the invention provide radiosensitization of human head and neck squamous cell carcinoma cells. For example, 48, 121, 135 and 195 show a concentration-dependent increase in radiosensitization (Figure 8, Table 18).

[0187] Compound 88, but not prodrug 234, provides radiosensitization of UT-SCC-54 C cells under aerobic conditions (Figure 9 and Table 18). On the other hand, under oxygen-deficient conditions, prodrug 234 is activated and radiosensitizing effect is obtained (SER=1.37, Figure 10). Similarly, compound 121, but not prodrug 248, provides radiosensitization of UT-SCC-54C cells under aerobic conditions. Under oxygen-deficient conditions, prodrug 248 is activated and produces a radiosensitizing effect (SER=1.82, Figure 10). Similarly, Compound 236, a prodrug of Compound 135, selectively provides sensitization of UT-SCC-54 C cells under oxygen deprivation (SER1.51, Figure 10). Similarly, prodrugs of compounds 236, 238, 250 and 251, compounds 88, 135, 121 and 122 selectively provide sensitizing effects on UT-SCC-54 C cells under oxygen deprivation, respectively (Figure 9 and Figure 10).

[0188] 5.3.9. Radiosensitization of UT-SCC-54C HNSCC Tumors When administered to mice bearing UT-SCC-54C tumor xenografts, compounds 121 and 248 alone inhibited tumor tissue production compared to DMSO control. No decrease was observed in clongen / g (Figure 11). The radiation (13Gy) alone causes approx. There was a 1.5 log reduction in clonogens / gram. Administration of compound 121 in combination with radiation (13 Gy) results in a significant (p=0.005) additional reduction in clongen / gram tumors compared to radiation alone. Prodrug 248 combination radiation showed a small but significant effect (p=0.018) compared to radiation alone. These studies demonstrated the efficacy of combined radiotherapy with DNA-PK inhibitors and their prodrugs in xenograft models of human head and neck tumors.

[0189] 5.3.10. UT-SCC-54C HNSCC tumor growth inhibition compound 121 showed less inhibition of tumor growth compared to individual vectors when administered to mice bearing UT-SCC-54C tumor xenografts ( Figure 12A). A single dose of radiation (10 Gy) can moderately slow tumor growth, while compound 121 can significantly inhibit tumor growth when administered in combination with radiation (FIG. 12B). These studies further demonstrated the therapeutic efficacy of the combination of DNA-PK inhibitors and radiotherapy in xenograft models of human head and neck tumors.

[0190] As mentioned above, compounds of formulas I, II, III, IV, V, VI and VII exhibit selectivity for DNA-PK. In one embodiment, the invention provides an IC for DNA-PK, as determined by the embodiment listed in Example 171. 50 Compounds of formula I, II, III, IV, V, VI and VII are provided which have a value of less than 500 nM.

[0191] In one aspect, the invention provides compounds of any of Formulas I, II, III, IV, V, VI and VII, having one or more of the following:

[0192] (a) IC for DNA-PK measured by quantifying phosphorylation of a peptide substrate by human DNA-PK in the presence of DNA and ATP 50 Value should be less than 500nM (b) Selectivity ratio for one or more PI3K isoforms exceeds 100× (c) The selection ratio for one or more PIKK kinases selected from the group consisting of mTOR, ATM, and ATR is greater than 100×. In one embodiment, compounds of the invention have an IC for DNA-PK. 50 The value is less than 400, 300, 200 or 100 nM. In one embodiment, a compound of the invention has a selectivity for one or more π3K isoforms greater than 200-fold, 300-fold, or 400-fold. In one embodiment, a compound of the invention has a selectivity for one or more PIKK kinases selected from the group consisting of mTOR, ATM, and ATR of greater than 200, 300, or 400×.

[0193] In one aspect, the invention provides a compound of any of Formula I, II, III or IV, having one or more of the following:

[0194] (a) The S50 value in combination with 3 Gy radiation for UT-SCC-54C HNSCC cells is less than 1 μM, as determined by the scheme described in Example 175. (b) the ability to increase the concentration of the compound to limit tumor cell proliferation, as determined by cell proliferation assay, with an S50 value of less than 1 μM in combination with 3 Gy radiation to UT-SCC-54C HNSCC cells; (c) SER at 1 μM when combined with radiation to UT-SCC-54c HNSCC cells determined by the scheme described in Example 178. 10 the value of exceeds 1.5, and (d) used at 1 μM in combination with radiation on UT-SCC-54C HNSCC cells in determining the ability of compounds to sensitize tumor cells to increased radiation doses by inhibiting clonogenic survival. When, SER 10 The value must be greater than 1.5 In one aspect, the present invention provides SER under oxygen-deficient conditions, as determined by the scheme listed in Example 178. 10 Provided are compounds of any of formulas V, VI and VII, wherein the value of is greater than 1.5.

[0195] In one aspect, the invention provides compounds 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 , 28, 29, 30, 31, 32, 33, 35, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52 , 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77 , 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 94, 95, 96, 97, 98, 99, 104, 105, 110, 115, 116, 121, 122, 123 , 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 141, 146, 147, 152, 153, 157, 162, 163, 167, 172, 173, 178 , 179, 184, 185, 190, 195, 196, 197, 198, 199, 200, 205, 206, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223 A compound selected from the group consisting of I will provide a.

[0196] In one embodiment of the invention, the invention provides a compound selected from the group consisting of 121, 125, 127, 135, 172, 225, 230, 238, 248 and 260.

[0197] Compounds of the invention can be made using the methods and processes described herein or similar methods and processes. Methods of obtaining the compounds described herein will be obvious to those skilled in the art; for example, suitable methods are described in the reaction schemes and references cited below. Note that when typical or preferred process conditions (e.g., reaction temperature, time, molar ratio of reactants, solvent, pressure, etc.) are indicated, other process conditions may be used unless otherwise specified. Please understand that this is also possible. Optimal reaction conditions can vary depending on the particular reactants used.

[0198] Conventional protecting groups may be necessary to prevent some functional groups from undergoing undesirable reactions. The need for protection and deprotection, as well as the selection of appropriate protecting groups, will be readily determined by those skilled in the art, as will the appropriate protecting groups for various functional groups, and the appropriate conditions for protection and deprotection of a particular functional group. (See, eg, T. W. Greene and G. M. Wuts, Protecting Groups in Organic Synthesis, 3rd edition, Wiley, New York, 1999).

[0199] Starting materials useful for these methods and reactions are commercially available or described in Fischer and Fischer's Organic Synthesis Reagents, Volumes 1-15 (John Wiley and Sons, 1991), Organic Reactions, Volumes 1-40 ( as described in standard reference works such as John Wiley and Sons, 1991), March's Advanced Organic Chemistry (John Wiley and Sons, 4th ed.), and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989). It can be prepared by known methods or modifications thereof.

[0200] Where appropriate, the various starting materials, intermediates and compounds can be isolated and purified using conventional techniques such as precipitation, filtration, crystallization, evaporation, distillation and chromatography. Characterization of compounds can be performed using conventional methods such as melting point, mass spectrometry, nuclear magnetic resonance, and various other spectroscopic analyses.

[0201] For example, a compound of formula I or a pharmacologically acceptable salt thereof may be [ka] It can be created according to the following general scheme.

[0202] First, 2,4-dichloro-5-nitropyridine and an amine are reacted to produce a compound of formula VIII. [ka] The amine may be an optionally substituted alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl or heteroarylamine. Other functional groups present in the amine may be protected according to standard protection strategies.

[0203] The compound of formula VIII is then reduced using a reducing agent such as tin chloride dihydrate or zinc powder, ammonium chloride to form a compound of formula IX. However, Y is defined as above. [ka] The Formula IX compound is then reacted with carbonyldiimidazole or a similar reagent to form a Formula X compound, where Y is defined as above. [ka] A compound of formula X is reacted with an optionally substituted alkyl, cycloalkyl, alkenylaryl or benzyl halide under basic conditions to form a compound of formula XI. Here, X and Y are defined as above. [ka] The compound of Formula XI is then reacted with an optionally substituted aryl or heteroaryl amine to form a compound of Formula I using an acid or palladium mediated catalyst.

[0204] From the compound of formula V, carbamoyl chloride of formula XII can be stably produced by reacting the compound of formula I with a carbamoylating agent such as phosgene, bisphosgene, triphosgene. This can be purified, isolated and reacted with various nitroaromatic alcohols to form carbamates of formula V. [ka] Compounds of formula VI can be prepared from compounds of formulas I-IV by reacting phenol and nitroheteroarylalkyl halide under basic conditions. Further examples of Formula VI compounds can be prepared by quaternizing appropriate tertiary amine side chains on Formula I-VI compounds with nitroheteroarylalkyl halides.

[0205] Some of the various ring substituents in the compounds of the invention may be introduced by standard aromatic substitution reactions, or may be generated by conventional functional group modifications, either before or immediately after the methods described above. Good things should be understood. For example, compounds of Formula I can be further converted to compounds of Formula I by standard aromatic substitution reactions or conventional functional group modifications. Such reactions and modifications include, for example, introduction of substituents by aromatic substitution reactions, reduction of substituents, alkylation of substituents, and oxidation of substituents. Reagents and reaction conditions for such methods are known in the chemical arts. Specific examples of aromatic substitution reactions include the introduction of nitro using concentrated nitric acid, the introduction of acyl using an acyl halide and a Lewis acid (e.g., aluminum trichloride) under Friedel-Crafts conditions, and the introduction of halogen groups. Includes the introduction of Examples of modifications include the reduction of nitro to amino, for example by nickel-catalyzed catalytic hydrogenation or iron treatment by heating in the presence of hydrochloric acid. Alkylthio is oxidized to alkylsulfinyl or alkylsulfonyl.

[0206] Referring to (1) below, 4-chloro-5-nitropyridin-2-ol (1) is treated with phosphorus oxychloride and tetramethylammonium chloride to obtain dichloride 2. Displacement of chloride 2 with cyclopentamine gives nitroamine 3, and reduction of tin chloride dihydrate 3 gives diamine 4. Reaction of 4 with carbonyldiimidazole yields pyridoimidazolone 5, which is alkylated with sodium hydride and methyl iodide to yield chloride 6. The chloride of 6 is replaced with aniline using Buchwald conditions to give compound 7.

[0207] [ka] Similarly, compound 8-81 is obtained by reacting chloride 6 with various anilines and heteroarylamines using Buchwald conditions (Scheme 2).

[0208] [ka] [Table 1-1] [Table 1-2] [Table 1-3] Nitro-substituted compounds 14-16 are reduced by Pd / C under hydrogen gas to give the corresponding anilines 82-84, respectively (Scheme 3).

[0209] [ka] [Table 2] Pd / C reduction of benzyl ethers 34-36 under hydrogen gas affords the corresponding phenols 85-87 (Scheme 4). Similarly, phenol 88 is obtained by reducing benzyl ether 51.

[0210] [ka] [Table 3] Alkylation of imidazolone 5 with NaH and various alkyl halides provides chlorides 89-93 (Scheme 5). Displacement of chloride 89-93 under Buchwald conditions gives the corresponding imidazopyridinone 94-98. 98 reduction of benzyl ether gives alcohol 99.

[0211] [ka] [Table 4] Chloride 2 is replaced with 2-methoxyethylamine to give nitroamine 100, and 100 is reduced with tin chloride dihydrate to give diamine 101 (Scheme 6). Reaction of 101 with carbonyldiimidazole yields pyridinoimidazolone 102, which is alkylated with sodium hydride and methyl iodide to yield chloride 103. The chloride of 103 is replaced with 4-methoxy-2-methylaniline or 4-chloro-2-methylaniline using Buchwald conditions to give the corresponding compounds 104 (SN39478) and 105 (SN39551).

[0212] [ka] Displacement of chloride 2 with oxetan-3-amine gives nitroamine 106, and reduction of 106 with tin chloride dihydrate gives diamine 107 (Scheme 7). Reaction of 107 with carbonyldiimidazole yields pyridinoimidazolone 108, which is alkylated with sodium hydride and methyl iodide to yield chloride 109. Displacement of the chloride of 109 with 4-methoxy-2-methylaniline using Buchwald conditions provides compound 110.

[0213] [ka] Displacement of chloride 2 with tetrahydrofuran-3-amine gives nitroamine 111, and reduction of 111 with tin chloride dihydrate gives diamine 112 (Scheme 8). Reaction of 112 with carbonyldiimidazole gives pyridinoimidazolone 113, which is alkylated with sodium hydride and methyl iodide to give chloride 114. The chloride of 114 is replaced with 4-methoxy-2-methylaniline or 4-chloro-2-methylaniline using Buchwald conditions to give the corresponding compounds 115 (SN39878) and 116 (SN39881).

[0214] [ka] Displacement of chloride 2 with tetrahydro-2H-pyran-4-amine gives nitroamine 117, and reduction of 117 with tin chloride dihydrate gives diamine 118 (Scheme 9). Reaction of 118 with carbonyldiimidazole gives pyridinoimidazolone 119, which is alkylated with sodium hydride and methyl iodide to give chloride 120. Displacement of the chloride of 120 with various amines using Buchwald conditions provides compounds 121-132.

[0215] [ka] [Table 5] Imidazopyridinone 121 and 122 with benzylchloroformate and iPr 2 Reaction with NEt gives the corresponding carbamates 133 (SN39689) and 134 (SN39690) (Scheme 10).

[0216] [ka] Benzyl ether 124 is reduced by Pd / C under hydrogen gas to give the corresponding phenol 135 (SN39872) (Scheme 11).

[0217] [ka] Ester 129 is hydrolyzed under basic conditions to give acid 136 (SN40071) (Scheme 12).

[0218] [ka]

[0219] Displacement of chloride 2 with (tetrahydro-2H-pyran-4-yl)methylamine gives nitroamine 137, and reduction of 137 with zinc powder and ammonium chloride gives diamine 138 (Scheme 13). Reaction of 138 with carbonyldiimidazole gives pyridinoimidazolone 139, which is alkylated with sodium hydride and methyl iodide to give chloride 140. The chloride of 140 is replaced with 4-methoxy-2-methylaniline using Buchwald conditions to yield compound 141 (SN39667).

[0220] [ka] Replacement of chloride 2 with 2-(tetrahydro-2H-pyran-4-yl)ethan-1-amine gives nitroamine 142, and reduction of 142 with zinc powder and ammonium chloride gives diamine 143 (Scheme 14) . Reaction of 143 with carbonyldiimidazole gives pyridinoimidazolone 144, which is alkylated with sodium hydride and methyl iodide to give chloride 145. Replacement of the chloride of 145 with 4-methoxy-2-methylaniline or 4-chloro-2-methylaniline and using Buchwald conditions gives the corresponding compounds 146 (SN39550) and 147 (SN39552).

[0221] [ka] Substitution of 4-aminopiperidine-1-carboxylic acid t-butyl chloride 2 gives nitroamine 148, and reduction of 148 with zinc powder and ammonium chloride gives diamine 149 (Scheme 15). Reaction of 149 with carbonyldiimidazole gives pyridinoimidazolone 150, which is alkylated with sodium hydride and methyl iodide to give chloride 151. The chloride of 151 is replaced with 4-methoxy-2-methylaniline using Buchwald conditions to give carbamate 152 (SN39598). Carbamate 152 is hydrolyzed under acidic conditions to yield compound 153 (SN39600) as the hydrochloride salt.

[0222] [ka] Reaction of imidazopyridinone 152 with benzoylchloroformic acid provides carbamate 154 (Scheme 16). Acid hydrolysis of 154 provides amine 155. Reductive amination of 155 with formaldehyde and sodium triacetoxyborohydride provides amine 156, which is converted to compound 157 (SN39686) under reducing conditions.

[0223] [ka]

[0224] Displacement of chloride 2 with t-butyl 4-(aminomethyl)piperidine-1-carboxylate gives nitroamine 158, and reduction of 158 with zinc powder and ammonium chloride gives diamine 159 (Scheme 17). Reaction of 159 with carbonyldiimidazole gives pyridinoimidazolone 160, which is alkylated with sodium hydride and methyl iodide to give chloride 161. The chloride of 161 is replaced with 4-methoxy-2-methylaniline using Buchwald conditions to give carbamate 162 (SN39627). Hydrolysis of carbamate 162 provides amine 163 (SN39628) as the hydrochloride salt.

[0225] [ka] Reaction of imidazopyridinone 162 with benzoylchloroformic acid provides carbamate 164 (Scheme 18). Acid hydrolysis of 164 provides amine 165. Reductive amination of 165 with formaldehyde and sodium triacetoxyborohydride provides amine 166, which is converted to compound 167 (SN39687) under reducing conditions.

[0226] [ka] Displacement of chloride 2 with 4-methoxycyclohexane-1-amine gives nitroamine 168, and reduction of 168 with tin chloride dihydrate gives diamine 169 (Scheme 19). Reaction of 169 with carbonyldiimidazole gives pyridinoimidazolone 170, which is alkylated with sodium hydride and methyl iodide to give chloride 171. Substitution of the chloride of 171 with 4-methoxy-2-methylaniline or 4-chloro-2-methylaniline and using Buchwald conditions gives the corresponding compounds 172 (SN39540) and 173 (SN39539).

[0227] [ka] Displacement of chloride 2 with 4-(benzyloxy)cyclohexane-1-amine gives nitroamine 174, and reduction of 174 with tin chloride dihydrate gives diamine 175 (Scheme 20). Reaction of 175 with carbonyldiimidazole gives pyridinoimidazolone 176, which is alkylated with sodium hydride and methyl iodide to give chloride 177. The chloride of 177 is replaced with 4-methoxy-2-methylaniline using Buchwald conditions to yield compound 178 (SN39581). Benzyl ether 178 is hydrogenolyzed to obtain alcohol 179 (SN39584).

[0228] [ka] Displacement of chloride 2 with t-butyl (4-aminocyclohexyl)carbamate gives nitroamine 180, and reduction of 180 with zinc powder and ammonium formate gives diamine 181 (Scheme 21). Reaction of 181 with carbonyldiimidazole gives pyridinoimidazolone 182, which is alkylated with sodium hydride and methyl iodide to give chloride 183. The chloride of 183 is replaced with 4-methoxy-2-methylaniline using Buchwald conditions to provide compound 184. Acid hydrolysis of carbamate 184 (SN40297) yields amine 185 (SN39695).

[0229] [ka] Displacement of chloride 2 with aniline gives nitroamine 186 and reduction of tin chloride dihydrate 186 gives diamine 187 (Scheme 22). Reaction of 187 with carbonyldiimidazole gives pyridinoimidazolone 188, which is alkylated with sodium hydride and methyl iodide to give chloride 189. The chloride of 189 is replaced with 4-methoxy-2-methylaniline using Buchwald conditions to give 190 (SN39623).

[0230] [ka] Displacement of chloride 2 with anisoamine gives nitroamine 191 and reduction of tin chloride dihydrate 191 gives diamine 192 (Scheme 23). Reaction of 192 with carbonyldiimidazole gives pyridinoimidazolone 193, which is alkylated with sodium hydride and methyl iodide to give chloride 194. The chloride of 194 is substituted with various anilines using Buchwald conditions to obtain compounds 195-199.

[0231] [ka] [Table 6] Benzyl ether 199 is reduced by Pd / C under hydrogen to give the corresponding phenol 200 (SN39530) (Scheme 24).

[0232] [ka] Displacement of chloride 2 with 4-(benzyloxy)aniline gives nitroamine 201, and reduction of 201 with tin chloride dihydrate gives diamine 202 (Scheme 25). Reaction of 202 with carbonyldiimidazole yields pyridinoimidazolone 203, which is alkylated with sodium hydride and methyl iodide to yield chloride 204. The chloride of 204 is replaced with 4-methoxy-2-methylaniline using Buchwald conditions to give compound 205 (SN39525). Pd / C reduction of benzyl ether 205 under hydrogen affords the corresponding phenol 206 (SN39528).

[0233] [ka] Displacement of chloride 2 with 2-(4-aminophenyl)-2-methylpropanenitrile gives nitroamine 207, and reduction of tin chloride dihydrate 207 gives diamine 208 (Scheme 26). Reaction of 208 with carbonyldiimidazole yields pyridinoimidazolone 209, which is alkylated with sodium hydride and methyl iodide to yield chloride 210. Using Buchwald conditions, the chloride of 210 is replaced with various anilines to obtain compounds 211-214.

[0234] [ka] [Table 7] Using improved Buchwald conditions, chloride 120 is replaced with another aniline group (Scheme 9) to give compounds 215-226 (Scheme 27).

[0235] [ka] [Table 8] Reaction of imidazopyridinone 124 with di-t-butyl dicarbonate provides carbamate 227 (Scheme 28). Hydrogenolysis of 227 yields phenol 228. Under basic conditions, 228 was alkylated with 2-chloro-N,N-dimethylethyl-1-aminochloride to give ether 229, which was protected under acidic conditions to give imidazopyridinone 230 (SN40558). obtain.

[0236] [ka] Reaction of imidazopyridinone 51 with di-t-butyl dicarbonate provides carbamate 231 (Scheme 29). Hydrogenolysis of 231 yields phenol 232. Alkylation of 232 with 5-(bromomethyl)-1-methyl-2-nitro-1H-imidazole under basic conditions afforded ether 233, which was protected under acidic conditions to yield prodrug 234 (SN39586). obtain.

[0237] [ka] Phenol 228 (Scheme 28) can be converted to 5-(chloromethyl)-1-methyl-2-nitro-1H-imidazole, 5-(1-chloroethyl)-1-methyl-2-nitro-1H-imidazole or (1- Alkylation with methyl-5-nitro-1H-imidazol-2-yl)methanol under basic conditions affords ethers 235, 237 and 238. Phenol 228 is also alkylated with (5-nitrothiophenol-2-yl)methanol under Mitsunobu conditions to give ether 241. Protection of esters 235, 237, 239 and 241 under acidic conditions affords prodrugs 236, 238 and 240 (Scheme 30).

[0238] [ka] [Table 9] Imidazopyridinone 199 is reacted with di-t-butyl dicarbonate to give carbamate 243 (Scheme 31). Hydrogenolysis of 243 yields phenol 244. Alkylation of 244 with 5-(chloromethyl)-1-methyl-2-nitro-1H imidazole under basic conditions afforded ether 245, which was protected under acidic conditions to yield prodrug 246 (SN39591). obtain.

[0239] [ka] Imidazopyridinone 48 with triphosgene and NaHCO 3 to form the intermediate carbamoyl chloride, followed by reaction with 5-(hydroxymethyl)-1-methyl-2-nitro-1H-imidazole to give prodrug 247 (SN39725) (Scheme 32).

[0240] [ka] Imidazopyridinone 121 with triphosgene and NaHCO 3 to form the intermediate carbamoyl chloride, followed by 5-(hydroxymethyl)-1-methyl-2-nitro-1H-imidazole, DMAP and K 2 C.O. 3 Prodrug 248 (SN39884) is obtained (Scheme 33). Process optimization was performed using 1-(1-methyl-2-nitro-1H-imidazol-5-yl)ethane-1-ol or (1-methyl-5-nitro-1H-imidazol-2-yl)methanol. Prior to reacting, intermediate carbamoyl chloride 249 is isolated to form prodrugs 250 (SN40425) and 251 (SN40353).

[0241] [ka] Imidazopyridinone 153 is reacted with (1-methyl-2-nitro-1H-imidazol-5-yl)methyl(4-nitrophenyl)carbonate to give prodrug 252 (SN40275) (Scheme 34).

[0242] [ka] Imidazopyridinone 185 is reacted with (1-methyl-2-nitro-1H-imidazol-5-yl)methyl(4-nitrophenyl)carbonate to give prodrug 253 (SN40302) (Scheme 35).

[0243] [ka] Imidazopyridinone 129, 225 and 130 with triphosgene and NaHCO 3 to form the intermediate carbamoyl chloride, followed by 5-(hydroxymethyl)-1-methyl-2-nitro-1H imidazole and Cs 2 C.O. 3 to obtain prodrugs 254-256 (Scheme 36).

[0244] [ka] [Table 10] Imidazopyridinone 122, 172 and 195 with triphosgene and NaHCO 3 to form the intermediate carbamoyl chloride, followed by 5-(hydroxymethyl)-1-methyl-2-nitro-1H imidazole and Cs 2 C.O. 3 to obtain prodrug 257-259 (Scheme 37).

[0245] [ka] [Table 11] After converting the imidazopyridinedione 230 to the free base, it is reacted with 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole to give the quaternary ammonium salt (SN40564) 260 (Scheme 38).

[0246] [ka] 5.4 Use of compounds of the invention in the treatment of cancer The demonstrated DNA-PK inhibitory activity of the compounds of the present invention makes them useful therapeutic agents against a range of diseases including cancer. In particular, the compounds of the invention are useful as antitumor agents. While not wishing to be bound by theory, the inventors believe that the DNA-PK inhibitor compounds described herein are sensitive to, or at least partially inhibit, DNA-PK. are believed to be useful as antiproliferative, apoptotic, and / or antiinvasive agents in the treatment or prevention of solid and liquid tumors mediated by

[0247] Accordingly, in one aspect, the present invention provides a method of treating a disease in which inhibition of DNA-PK is beneficial in a subject, the method comprising: A method is provided comprising administering to a subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof.

[0248] In another aspect, the invention provides a compound of formula I, II, III, IV, V, VI or VII or its pharmaceutical composition in the manufacture of a medicament for the treatment of diseases in which inhibition of DNA-PK is beneficial. Provide for the use of acceptable salts.

[0249] In another aspect, the invention provides a compound of formula I, II, III, IV, V, VI or VII, or a pharmaceutically acceptable salt thereof, for treating diseases in which inhibition of DNA-PK is beneficial. I will provide a.

[0250] In one embodiment, the disease is cancer.

[0251] In one embodiment, the cancer is a solid tumor including, but not limited to, carcinoma, sarcoma, leukemia, and lymphoid malignancies.

[0252] In one embodiment, the cancer is leukemia (including chronic lymphocytic leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, multiple myeloma); lymphoma, such as Hodgkin's disease, non-Hodgkin's lymphoma (including mantle cell lymphoma); and myelodysplastic syndromes; and solid tumors and their metastatic cancers, such as breast cancer, lung cancer (non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma), endometrial cancer, uterine cancer. Endometrial cancer; glioma, dysembryoplastic neuroepithelial tumor, glioblastoma multiforme, mixed glioma, medulloblastoma, retinoblastoma, neuroblastoma, germinoma and teratoma, etc. tumors of the gastrointestinal tract, such as central nervous system tumors, stomach cancer, esophageal cancer, hepatocellular (liver) cancer, bile duct cancer, colon and rectal cancer, small intestine cancer, and pancreatic cancer; melanoma (especially metastatic melanoma) Skin cancer, thyroid cancer, head and neck cancer, cancer of the salivary glands, bile duct, bone, prostate, testicles, ovaries, cervix, uterus, vulva, bladder, kidney (renal cell cancer, clear cell cancer, and kidney tumors) including cell carcinoma), squamous cell carcinoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, soft tissue sarcoma Ewing's sarcoma, gastrointestinal stromal tumor (GIST), Kaposi's sarcoma, and rhabdomyosarcoma and neuroblastoma. Selected from the group consisting of childhood cancer.

[0253] In one embodiment, the cancer is a tumor that contains a significantly hypoxic fraction.

[0254] In one embodiment, the cancer is selected from the group consisting of squamous cell carcinoma (including head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC)), pancreatic ductal adenocarcinoma, cervical cancer, and prostate cancer.

[0255] The methods of the invention involve administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof. .

[0256] A therapeutically effective amount is one that produces any observable or measurable change in a subject, as described in the definitions of "therapy," "treatment," and "prophylaxis" above. can be caused.

[0257] For example, in the treatment of cancer, a therapeutically effective amount of a compound of the invention may reduce the number of cancer or tumor cells, reduce the overall size of the tumor, e.g. inhibiting or inhibiting the invasion of tumor cells, inhibiting or inhibiting the metastasis of a tumor, inhibiting or inhibiting the growth of a tumor, alleviating to some extent one or more symptoms associated with cancer, the onset of cancer; reduction in mortality and mortality, improvement in quality of life, or a combination of these effects.

[0258] The effectiveness of treatment can be measured by assessing survival, time to disease progression (TTP), remission rate (RR), duration of remission, and / or quality of life.

[0259] The therapeutically effective amount may vary depending on the route of administration, use of excipients, and co-administration with other drugs. For example, when using combination therapy, the amount of a compound or pharmaceutically acceptable salt of the invention described herein and the other pharmaceutically active drug, when combined, Together, the target disease in the subject can be effectively treated.

[0260] Accordingly, anti-cancer effects useful in treating cancer in a subject include, but are not limited to, anti-tumor effects, response rates, time to disease progression, and survival rates. The antitumor effects of the treatment methods of the present invention include inhibition of tumor growth, delay of tumor growth, tumor regression, tumor shrinkage, increased time to tumor regrowth when treatment is discontinued, and slowing of disease progression. including, but not limited to, delays. Anticancer effects include not only preventive treatment but also treatment of existing diseases.

[0261] In addition to administering a compound of the invention, the treatment methods of the invention can include other treatments including, but not limited to, radiation therapy and / or chemotherapy.

[0262] Radiation therapy may include one or more of the following treatment categories:

[0263] (a) external radiotherapy using electromagnetic radiation and intraoperative radiotherapy using electromagnetic radiation; (b) internal or brachytherapy, interstitial or intraluminal radiotherapy, and (c) Whole body radiotherapy including but not limited to iodine-131 and strontium-89.

[0264] Modern radiation therapy is generally delivered by linear accelerators that generate high-energy x-rays that can be collimated to form a treatment field. Intensity-modulated radiation therapy (IMRT) uses non-uniform, computer-controlled radiation fields to optimize delivery to tumor tissue rather than surrounding normal tissue. Standard fractionated radiotherapy (FRT) is usually given in small doses (1.8-2.0 Gy) totaling 30-70 Gy over a period of 4-7 weeks. Improvements in treatment planning and delivery have enabled hypofractionated radiotherapy, which can deliver small, high doses (15-20 Gy) to tumors. This is called stereotactic body radiotherapy (SBRT) or stereotactic ablation brain radiotherapy (SABR). High energy charged particles such as protons and carbon ions are also useful in tumor treatment and have the advantage of transmitting most of the particle energy within the tumor. Brachytherapy uses radioactive implants to deliver radiation therapy inside the patient and is sometimes called intraoperative radiation therapy (IORT).

[0265] Chemotherapy may include one or more of the following types of anti-tumor agents:

[0266] (a) antineoplastic agents and combinations thereof, such as DNA alkylating agents (e.g., nitrosoureas such as cisplatin, oxaliplatin, carboplatin, cyclophosphamide, isophosphamide, bendamostine, melphalan, chlorambucil, busulfan, temozolomide, and carmostin); antimetabolites (e.g. gemcitabine and antifolates, fluoropyrimidines such as 5-fluorouracil and tegafur, raltitrexed, methotrexate, cytosine arabinoside and hydroxyurea); antitumor antibiotics (e.g. anthracycline antibiotics (e.g., adriamycin, bleomycin, doxorubicin, liposomal doxorubicin, pirarubicin, daunomycin, valrubicin, epirubicin, idarubicin, mitomycin-C, dactinomycin, amrubicin, mithramycin); antimitotic drugs (e.g., vincristine); , vincrisialalkaloids such as vinblastine, vindesine, and vinorelbine; drugs of the paclitaxel family such as taxol and taxotere, and pokinase inhibitors); dophyllotoxin); DNA repair mechanism inhibitors such as CHK kinase; ATM inhibitors (such as AZD 0156 and AZD 1390); poly(ADP-ribose) polymerase inhibitors (PARP inhibitors, including olaparib); tanespimycin and Hsp90 inhibitors such as letaspimycin; ATR kinase inhibitors (e.g. AZD6738) and WEE1 kinase inhibitors (e.g. AZD1775 / MK-1775); and (b) in vivo and in vivo methods to increase the immunogenicity of patient tumor cells, such as transfection with cytokines such as interleukin 2, interleukin 4 or granulocyte-macrophage colony stimulating factor; Immunotherapy including both methods of reducing T cell incompetence or modulating T cell function; CTLA4 (e.g., ipilimumab and tremelimumab), B7H1, PD-1 (e.g., BMS-936558 or AMP -514), methods of enhancing T cell responses against tumors, such as blocking antibodies against PD-L-1 (e.g., MEDI4736 (durvalumab)), and agonist antibodies against CD137; methods using transfected immune cells such as; methods using tumor cell lines transfected with cytokines; methods using antibodies against tumor-associated antigens and antibodies that deplete target cell types (e.g., unconjugated antibodies such as rituximab); anti-CD20 antibodies, radiolabeled anti-CD20 antibodies Bexxar and Zevalin, and anti-CD54 antibodies Campath); methods of using anti-idiotypic antibodies; methods of enhancing natural killer cell function; antibody-toxin conjugates (e.g., anti-CD33 antibodies); mylotarg); immunotoxins such as mocetumomab passodotox; agonists of toll-like receptor 7 or toll-like receptor 9. In one embodiment, the invention provides a therapeutically effective amount of a compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, in combination with radiation therapy. administering to the subject a compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, concurrently, alone, or sequentially with radiation therapy. A method for treating cancer is provided.

[0267] In one embodiment, the radiation therapy is administered before, during, or after administration of the compound of Formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof. , administered to the subject.

[0268] In one embodiment, the present invention provides a compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for treating cancer. provide the use of something;

[0269] In one embodiment, the agents of the invention are used for administration simultaneously, alone, or sequentially with radiation therapy.

[0270] In one embodiment, the radiation therapy is selected from the group consisting of IMRT, FRT, SBRT, SABR, and IORT.

[0271] In one embodiment, a therapeutically effective amount of a compound of Formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, is administered in combination with chemotherapy. and administering a compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, simultaneously with chemotherapy, alone or sequentially. provide a method.

[0272] In one embodiment, chemotherapy is administered before, during, or after administration of a compound of Formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof. , administered to the subject.

[0273] In one embodiment, the present invention provides a compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for treating cancer. provide the use of something;

[0274] In one embodiment, the agents of the invention are used for administration simultaneously, alone, or sequentially with chemotherapy.

[0275] Generally, the compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, will be administered at 2.5 to 5000 mg / m 2 is administered to the subject in unit doses within the range of animal body area or approximately 0.05 to 100 mg / kg. Unit dosage forms such as tablets or capsules generally contain, for example, 0.1 to 250 mg of active agent. Dosages should be varied depending on the subject being treated, the particular route of administration, any concomitant administration therapy, and the severity of the disease being treated. The optimal dosage will be determined by the subject's treating physician.

[0276] The compounds of the invention can be administered by any of a number of routes of administration, including oral administration (e.g., aqueous or non-aqueous solutions or suspensions, tablets for lingual administration, pills, powders, etc.). sublingually; anally, rectally or vaginally (e.g. pessaries, creams or foams); parenterally (e.g. as a sterile solution or suspension, intramuscularly, intravenously, subcutaneously or intrathecally); nasal; intraperitoneal; subcutaneous; transdermal (e.g., as a patch applied to the skin) or topically (e.g., as a cream, ointment, spray applied to the skin); . At least one compound and / or salt described herein can also be formulated for inhalation.

[0277] In another aspect, the invention provides a compound of formula I, II, III, IV, V, VI, or VII, or a pharmaceutically acceptable salt or solvate thereof, with one or more pharmaceutically acceptable salts or solvates thereof. A pharmaceutical composition comprising in combination with an excipient is provided.

[0278] The pharmaceutical compositions of the present invention can be formulated into dosage unit formulations for oral, topical, parenteral, inhalation, spray, or rectal administration. The term "injectable administration" includes intravenous, intramuscular, subcutaneous and parenteral injection, as well as the use of infusion techniques. The one or more compounds may be present in combination with one or more non-toxic pharmaceutically acceptable carriers and optionally other active ingredients.

[0279] "Pharmaceutically acceptable carrier" means a pharmaceutically acceptable carrier such as a liquid, diluent, excipient, filler, solvent, or encapsulating material that participates in the transport of the subject compound in vivo. material, composition or vehicle. Each carrier is considered "acceptable" because it is compatible with the other ingredients of the formulation and is not harmful to the subject. Pharmaceutically acceptable compositions of the invention can further include other active agents that provide additional therapeutic functions.

[0280] Examples of substances that can be used as pharmaceutically acceptable carriers include (1) sugars such as lactose, glucose and sucrose; (2) starches such as corn starch and potato starch; (3) cellulose and derivatives thereof (e.g. sodium carboxymethylcellulose, ethylcellulose, cellulose acetate); (4) sawdust; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository waxes. (9) Oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, soybean oil; (10) Ethylene glycols such as propylene glycol; (11) Glycerin, sorbitol, mannitol, polyethylene glycols, etc. polyhydric alcohols; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogens. (17) Isotonic saline; (18) Ringer's solution; (19) Ethanol; (20) Phosphate buffer; (21) Other non-toxic compatibility used in pharmaceutical formulations including, but not limited to, substances. Reference Remington: Science and Practice of Pharmacy, 20th Edition, (edited by Alfonso R. Gennaro), 2000.

[0281] Pharmaceutical compositions intended for oral administration may be prepared according to any suitable method known in the art; such compositions may be diluted to provide a palatable formulation. The composition may include one or more agents selected from the group consisting of agents, sweeteners, flavoring agents, coloring agents, and preservatives. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients that are suitable for the manufacture of tablets. These excipients include, for example, calcium carbonate, sodium carbonate, lactose, inert diluents such as calcium or sodium phosphate, granulating and disintegrating agents such as cornstarch or alginic acid, magnesium stearate, stearic acid, talc. It may also be a binder such as. Tablets may be uncoated or they may be coated by known techniques to delay disintegration and adsorption in the gastrointestinal tract and provide a sustained action over a longer period of time. For example, delay materials such as glyceride monostearate and glyceride distearate can be used. These compounds can also be manufactured in solid, rapid release form.

[0282] Oral formulations may be hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent (e.g. calcium carbonate, calcium phosphate, kaolin) or in a water or oil vehicle (e.g. peanut oil, liquid paraffin, It may also be a soft gelatin capsule mixed with olive oil).

[0283] Aqueous suspensions contain a mixture of the active materials with excipients suitable for the manufacture of aqueous suspensions. These excipients are, for example, suspending agents such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum granoco, gum arabic; naturally occurring phospholipids, such as lecithin, condensates with fatty acids; or alkylene oxides, such as polyoxyethylene stearate, condensates of ethylene oxide and long-chain fatty alcohols, such as hexadecinoloxycetyl alcohol, or condensates of ethylene oxide and partial esters derived from fatty acids and hexanol, such as poly A dispersing or wetting agent which may be oxyethylene sorbitol monooleate or a condensate of ethylene oxide with a partial ester derived from a fatty acid and hexanoic anhydride, such as a condensate with polyethylene sorbitol monooleate. be. The aqueous suspension may further contain one or more preservatives such as ethyl or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents such as chocolate. May contain sugars or saccharin.

[0284] Dispersible powders and particles suitable for preparing an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent, and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are, for example, those mentioned above. Additional excipients such as sweetening agents, flavoring agents, coloring agents, etc. may also be present.

[0285] The pharmaceutical composition of the present invention may be formulated as an oil suspension, which can be formulated by suspending the active ingredient in vegetable oil (e.g., peanut oil, olive oil, sesame oil, peanut oil) or mineral oil (e.g., liquid paraffin). It may also be in the form of a non-aqueous liquid preparation. The oily suspensions may contain a thickening agent, such as beeswax, hard paraffin, cetyl alcohol. By adding sweeteners and seasonings as described above, it is possible to provide a palatable oral preparation. These compositions can be preserved by adding antioxidants such as ascorbic acid.

[0286] Pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions.

[0287] The oil phase may be a vegetable oil, such as olive oil or peanut oil, or a mineral oil, such as liquid paraffin, or a mixture thereof. Suitable emulsifiers are natural gums such as gum arabic or gum furanoco, soybean, natural phospholipids such as lecithin, and esters or partial esters derived from fatty acids and hexanoic anhydride, such as dehydrated sorbitol monooleate. , and a condensate of ethylene oxide with a partial ester such as polyoxyethylene dehydrated sorbitol monooleate. The emulsion may contain sweeteners and seasonings.

[0288] The pharmaceutical compositions described herein for rectal, vaginal, or urethral administration can be provided as suppositories, which contain one or more compounds or salts, such as cocoa butter, It is prepared by mixing with one or more suitable non-irritating excipients or carriers, including polyethylene glycol, suppository wax or salicylates, and is solid at room temperature but liquid at body temperature, so that the active compound is melted and released within the rectum or vaginal cavity.

[0289] The pharmaceutical compositions described herein can be formulated for delivery via a catheter, stent, wire, or other intraluminal device. Delivery by such devices may be particularly useful for delivery to the bladder, urethra, ureters, rectum or intestines.

[0290] Dosage forms that are administered topically or transdermally include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The active compound can be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that are required. Ointments, pastes, creams and gels may contain excipients such as animal and vegetable fats, oils, waxes, paraffins, starches, xanthocombs, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or Can include mixtures thereof.

[0291] Powders and sprays can contain, in addition to the compounds described herein, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures thereof. . Propellants may also include conventional propellants such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons such as butane and propane.

[0292] Transdermal patches have the added advantage of providing controlled delivery to the body. Such dosage forms can be prepared by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux across the skin. The rate of such flux can be controlled by providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. The ophthalmic preparations, ophthalmic ointments, powders, solutions, etc. of the present invention can also contain at least one compound or salt described herein.

[0293] Pharmaceutical compositions according to the invention suitable for parenteral administration include at least one compound of the invention, or a pharmaceutically acceptable salt thereof, in one or more pharmaceutically acceptable sterile or Contains non-aqueous solutions, dispersions, suspensions or emulsions, or in combination with sterile powders to reconstitute sterile injectable solutions or dispersions before use, antioxidants, buffers, bacteriostatic agents , solutes or suspensions, or thickening agents that make the formulation isotonic with the blood of the intended recipient.

[0294] Examples of suitable aqueous and non-aqueous carriers useful in pharmaceutical compositions include water, ethanol, polyhydric alcohols (e.g., glycerin, propylene glycol, polyethylene glycol, etc.) and suitable mixtures thereof, vegetable oils such as olive oil, oleic acid, etc. Injectable organic esters such as ethyl acid. Proper fluidity can be maintained, for example, by the use of coatings such as lecithin, by maintaining the desired particle size in the case of dispersions, and by the use of surfactants.

[0295] These compositions can further contain adjuvants such as preservatives, wetting agents, emulsifying agents, dispersing agents, and the like. By containing various antibacterial and antifungal agents such as p-hydroxybenzoic acid ester, chlorobutanol, phenol sorbic acid, and chelating agents, the control effect against microorganisms can be ensured.

[0296] In some embodiments, tonicity agents such as sugars, sodium chloride, and the like can be included in the composition. Additionally, extended absorption in the injectable form can be accomplished by including delayed absorption agents such as aluminum monostearate and gelatin.

[0297] 6.Example The following examples represent the invention and detailed methods of making these compounds. However, the scope of the invention is not limited to these examples.

[0298] All final products were analyzed using an Achilen 1260 Infinity reverse phase HPLC (ZORBAX Eclipse XDB C 8 5 μm column, 4.6 × 150 mm; Agilent Technologies) equipped with a diode array detector. Mobile phase was 80% acetonitrile / 20% H in 45mM ammonium formate at pH 3.5 and 0.8mL / min. 2 It is a gradient of O(v / v). The final compound purity is determined by monitoring at 330±50 nM and is >95%. The melting point is determined using an electrothermal 2300 melting point apparatus. At 400MHz on a Bruker Avance 400 spectrometer 1 An NMR spectrum of the H spectrum was obtained. Chemical shifts are reported in ppm and coupling constants in Hz. Low-resolution mass spectra were collected by directly injecting the methanol solution into an Agilent 6120 mass spectrometer using atmospheric pressure chemical ionization (APCI) mode with a fragmentor voltage of 50 V and a drying gas temperature of 250 °C. High-resolution mass spectra (HRMS) were measured on an Agilent Technologies 6530 Accurate-Mass Quadrupole Time of Flight (Q-TOF) LC / MS coupled with an Agilent Jet Stream electrospray ionization (ESI) source, with the Detection becomes possible. MgSO organic solution 4 Or Na 2 S.O. 4 and evaporate the solvent under reduced pressure on a rotary evaporator. Thin layer chromatography was performed using aluminum-lined silica gel plates (Merck 60 F 254 ), UV light (254 nm) or I 2 The components were visualized by exposure to. Column chromatography was performed on silica gel (Merck 230-400 mesh). BrettPhos G3 is [(2-di-cyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1, 1'-biphenyl)]palladium(II) methanesulfonate, CDI is carbonyldiimidazole, Cs 2 C.O. 3 is cesium carbonate, DCM is dichloromethane, DIPEA is diisopropylethylamine, DMAP is 4-dimethylaminopyridine, DMF is dimethylformamide, DMSO is dimethyl sulfoxide, EtOAc is ethyl acetate, EtOH is ethanol, MeOH is methanol, MeCN is acetonitrile, MgSO 4 is magnesium sulfate, NMP is N-methylpyrrolidone, Pd 2 dba 3 is tris(dibenzylideneacetone)dipalladium(0), pet.ether is petroleum ether boiling distillate at 40~60℃, THF is tetrahydrofuran, and XPhos is 2-dicyclohexylphosphino-2',4',6'-triisopropyl. Refers to biphenyl.

[0299] Example 1: SN39228 1-Cyclopentyl-3-methyl-6-(phenylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (7) [ka] 2,4-dichloro-5-nitropyridine (2): 4-chloro-5-nitropyridin-2-ol (1) (5.38g, 30.8mmol), POCl 3 and tetramethylammonium chloride (10.1 g, 32.5 mmol) was stirred at 120° C. for 3 hours. The mixture was cooled, poured into ice / water (500 mL), and stirred at 0-10° C. for 1 hour. The mixture was extracted with DCM (3 x 100 mL) and the combined organic extracts (MgSO 4 ) and dried. The solution was filtered through a neutral alumina column and washed with DCM (50 mL). Evaporation of the solvent gave nitropyridine 2 (5.43 g, 91%) as a clear oil. 1 H NMR (CDCl 3 ) δ 8.97 (s,1 H,H-6),7.59 (s,1 H,H-3); MS m / z 192.9 (MH + ,100%),194.9 (MH + ,70%). 2-chloro-N-cyclopentyl-5-nitropyridin-4-amine (3): nitropyridine 2 (1.76 g, 9.12 mmol) and 2 To a stirred solution of NEt (1.87 mL, 10.94 mmol) in dry DCM (5 mL) at 5°C was added cyclopentamine (0.95 mL, 9.6 mmol) dropwise. The mixture was stirred at 20°C for 16 h, then diluted with DCM (100 ml), washed with water (3 x 50 ml) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography to give amine 3 (2.25 g, 100%) as a yellow oil, eluting with 10% EtOAc / petroleum ether. 1 H NMR (CDCl 3 ) δ 9.01 (s,1 H,H-6),8.17 (br s,1 H,4-NH),6.76 (s,1 H,H-3),3.93 (br dpent,J = 6.7,5.3 Hz ,1 H,NCH),2.10-2.18 (m,2 H,CH 2 ),1.70-1.88 (m,4 H,2 × CH 2 ),1.59-1.69 (m,2 H,CH 2 ); MS m / z 242.1 (MH + ,100%),244.1 (MH + ,35%). 6-chloro-N 4 -Cyclopentylpyridine-3,4-diamine (4): SnCl in EtOAc (100ml) 2 ·2H 2 To a suspension of O (7.16 g, 31.7 mmol) was added dropwise a solution of nitropyridine 3 (1.92 g, 7.93 mmol) in EtOAc (20 ml) at a temperature below 60°C. The mixture was stirred at 60°C for 2 hours, then cooled to 5°C and concentrated (solution). NH until this solution becomes basic (pH 9). 3 solution was added. The precipitate was filtered and washed with EtOAc (100 mL). The combined organic fractions were dried (MgSO 4 ), filtered and evaporated the solvent to obtain diamine 4 as a white powder. mp 103-105 °C; 1 H NMR [(CD 3 ) 2 SO] δ 7.35 (s,1 H,H-2),6.29 (s,1 H,H-5),5.48 (d,J = 6.2 Hz,1 H,4-NH),4.78 (br s,2 H,3-NH 2 ),3.75 (br dpent,J = 6.7,5.3 Hz,1 H,NCH),1.90-1.98 (m,2 H,CH 2 ),1.62-1.72 (m,2 H,CH 2 ),1.42-1.60 (m,4 H,2 × CH 2 ); MS m / z 212.2 (MH +,100%),214.2 (MH + ,35%).Anal calcd for C 10 H 14 ClN 3 ·0.1 EtOAc: C,56.65; H,6.77; N,19.06. Found: C,56.66; H,6.84; N,19.20%. 6-Chloro-1-cyclopentyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (5): Stirred diamine 4 (1.69 g, 7.98 mmol) in dry MeCN (80 ml). CDI (1.36 g, 8.38 mmol) was added to the solution at 20°C. The mixture was stirred at 20°C for 96 hours. Evaporate the solvent and dissolve the residue in CHCl 3 (150 mL) and water (100 mL). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was precipitated from 50% EtOAc / petroleum ether to give pyridinone 5 (1.80 g, 95%) as a white powder. mp 222-224 °C; 1 H NMR (CDCl 3 ) δ 9.76 (br s,1 H,3-NH),8.13 (s,1 H,H-4),7.01 (s,1 H,H-7),4.79 (pent,J = 8.7 Hz,1 H ,1-CH),1.94-2.12 (m,6 H,3 × CH 2 ),1.72-1.81 (m,2 H,CH 2 ); MS m / z 238.2 (MH + ,100%),240.2 (MH + ,35%).Anal calcd for C 11 H 12 ClN 3 O: C,55.59; H,5.09; N,17.68. Found: C,55.31; H,5.16; N,17.61%. 6-chloro-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (6): Pyridinone 5 (1.68 g, 7.1 mmol) stirred at 5°C ) and MeI (0.57 ml, 9.2 mmol) in dry DMF (20 ml) was added NaH (60% dispersion, 312 mg, 7.8 mmol). The mixture was stirred at 20° C. for 16 hours and then quenched with ice / water (5 mL). The solvent was evaporated and the residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-50%) of EtOAc / petroleum ether to give chloride 6 as white crystals. mp 141-142 °C; 1 H NMR (CDCl 3 ) δ 7.98 (s,1 H,H-4),6.98 (s,1 H,H-7),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.44 (s,3 H, 3-CH 3 ),1.92-2.07 (m,6 H,3 × CH 2 ),1.69-1.79 (m,2 H,CH 2 ); MS m / z 252.2 (MH + ,100%),254.2 (MH + ,35%).Anal calcd for C 12 H 14 ClN 3 O: C,56.26; H,5.61; N,16.69. Found: C,57.26; H,5.68; N,16.86%. 1-Cyclopentyl-3-methyl-6-(phenylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (7): chloride 6 (120 mg, 0.48 mmol), Aniline (53mg, 0.57mmol), Pd 2 dba 3 (22mg, 24μmol), XPhos(46mg, 96μmol)Cs 2 C.O. 3 A degassed mixture of (313 mg, 0.96 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-60%) of EtOAc / petroleum ether to give imidazopyridinone 7 (84 mg, 57%) as a tan powder. mp (EtOAc / pet ether) 168-170 °C; 1 H NMR (CDCl 3 ) δ 7.83 (s,1 H,H-4),7.33 (br dd,J = 8.6,7.2 Hz,2 H,H-3',H-5'),7.26 (br d,J = 8.6 Hz, 2 H,H-2',H-6'),7.01 (tt,J = 7.2,1.2 Hz,1 H,H-4'),6.64 (s,1 H,H-7),6.48 (s, 1 H,6-NH),4.77 (pent,J = 8.8 Hz,1 H,1-CH),3.40 (s,3 H,3-CH 3 ),1.95-2.05 (m,4 H,2 × CH 2 ),1.81-1.90 (m,2 H,CH 2 ),1.63-1.72 (m,2 H,CH 2 ); MS m / z 309.2 (MH + ,100%).Anal calcd for C 18 H 20 N 4 O: C,70.11; H,6.54; N,18.17. Found: C,70.06; H,6.64; N,18.23%. HPLC purity 100.0%.

[0300] Example 2: SN39229 1-Cyclopentyl-3-methyl-6-(4-methylphenylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (8) [ka] Chloride 6 (120 mg, 0.48 mmol), 4-methylaniline (61 mg, 0.57 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (313 mg, 0.96 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-60%) of EtOAc / petroleum ether to give imidazopyridinone 8 (99 mg, 64%) as a tan powder. mp (EtOAc / pet ether) 153-154 °C; 1 H NMR (CDCl 3 ) δ 7.80 (s,1 H,H-4),7.12-7.17 (m,4 H,H-2',H-3',H-5',H-6'),6.58 (d,J = 0.6 Hz,1 H,H-7),6.39 (s,1 H,6-NH),4.75 (pent,J = 8.8 Hz,1 H,1-CH),3.38 (s,3 H,3-CH 3 ),2.33 (s,3 H,4’-CH 3 ),1.95-2.03 (m,4 H,2 × CH 2 ),1.82-1.90 (m,2 H,CH 2 ),1.66-1.72 (m,2 H,CH 2 ). Anal calcd for C 19 H 22 N 4 O: C,70.78; H,6.88; N,17.38. Found: C,70.39; H,7.21; N,17.43%. HPLC purity 98.5%.

[0301] Example 3: SN39231 1-cyclopentyl-3-methyl-6-(3-methylphenylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (9) [ka] Chloride 6 (120 mg, 0.48 mmol), 3-methylaniline (61 mg, 0.57 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (311 mg, 0.96 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-70%) of EtOAc / petroleum ether to give imidazopyridinone 9 (131 mg, 85%) as a tan powder. mp (EtOAc / pet ether) 124-126 °C; 1H NMR (CDCl 3 ) δ 7.82 (d,J = 0.6 Hz,1 H,H-4),7.21 (br t,J = 7.7 Hz,1 H,H-5'),7.03-7.10 (m,2 H,H-2 ',H-6'),6.85 (d,J = 7.5 Hz,1 H,H-4'),6.68 (d,J = 0.6 Hz,1 H,H-7),6.44 (s,1 H, 6-NH),4.80 (pent,J = 8.8 Hz,1 H,1-CH),3.97 (s,3 H,3-CH 3 ),2.34 (s,3 H,3’-CH 3 ),1.94-2.05 (m,4 H,2 × CH 2 ),1.82-1.90 (m,2 H,CH 2 ),1.66-1.74 (m,2 H,CH 2 ).Anal calcd for C 19 H 22 N 4 O: C,70.78; H,6.88; N,17.38. Found: C,70.50; H,6.99; N,17.56%. HPLC purity 99.7%.

[0302] Example 4: SN39232 1-Cyclopentyl-3-methyl-6-(2-methylphenylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (10) [ka] Chloride 6 (120 mg, 0.48 mmol), 2-methylaniline (61 mg, 0.57 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (311 mg, 0.96 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-70%) of EtOAc / petroleum ether to give imidazopyridinone 10 (131 mg, 85%) as a tan foam. 1 H NMR (CDCl 3 ) δ 7.81 (d,J = 0.6 Hz,1 H,H-4),7.39 (d,J = 7.6 Hz,1 H,H-3'),7.24 (d,J = 7.4 Hz,1 H,H -6'),7.20 (br t,J = 7.7 Hz,1 H,H-4'),7.02 (dt,J = 7.4,1.1 Hz,1 H,H-5'),6.45 (d,J = 0.6 Hz,1 H,H-7),6.13 (s,1 H,6-NH),4.73 (pent,J = 8.8 Hz,1 H,1-CH),3.39 (s,3 H,3-CH 3 ),2.29 (s,3 H,3’-CH 3 ),1.92-2.02 (m,4 H,2 × CH 2 ),1.74-1.84 (m,2 H,CH 2 ),1.62-1.70 (m,2 H,CH 2 ); MS m / z 323.2 (MH + ,100%).Anal calcd for C 19 H 22 N 4 O·1 / 4EtOAc: C,70.35; H,6.94; N,16.92. Found: C,70.34; H,7.10; N,16.77%. HPLC purity 97.7%.

[0303] Example 5: SN39236 1-cyclopentyl-6-((4-methoxyphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (11) [ka] Chloride 6 (128 mg, 0.51 mmol), 4-methoxyaniline (75 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (331 mg, 1.02 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 11 (72 mg, 42%) as a brown powder. mp (EtOAc / pet ether) 159-161 °C; 1 H NMR (CDCl 3 ) δ 7.77 (s,1 H,H-4),7.21 (ddd,J = 8.9,3.5,2.2 Hz,2 H,H-2',H-6'),6.91 (ddd,J = 8.9,3.5 ,2.2 Hz,2 H,H-3',H-5'),6.42 (s,1 H,H-7),6.27 (br s,1 H,6-NH),4.72 (pent,J = 8.8 Hz,1 H,1-CH),3.82 (s,3 H,4'-OCH 3 ),3.38 (s,3 H,3-CH 3 ),1.93-2.02 (m,4 H,2 × CH 2 ),1.78-1.88 (m,2 H,CH 2 ),1.63-1.72 (m,2 H,CH 2 ); MS m / z 339.2 (MH + ,100%).Anal calcd for C 19 H 22 N 4 O 2 ·1 / 4EtOAc: C,66.65; H,6.71; N,15.54. Found: C,66.29; H,6.57; N,15.90%. HPLC purity 98.1%.

[0304] Example 6: SN39239 1-cyclopentyl-6-((3-methoxyphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (12) [ka] Chloride 6 (126 mg, 0.50 mmol), 3-methoxyaniline (74 mg, 0.60 mmol), Pd 2 dba 3 (23mg, 25μmol), XPhos (47mg, 102μmol), Cs 2 C.O. 3 A degassed mixture of (326 mg, 1.02 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 12 (136 mg, 80%) as a tan powder, eluting with EtOAc. mp (EtOAc / pet ether) 66-69 °C; 1 H NMR (CDCl 3 ) δ 7.83 (d,J = 0.4 Hz,1 H,H-4),7.22 (t,J = 8.1 Hz,1 H,H-5'),6.89 (t,J = 2.3 Hz,1 H,H -2'),6.82 (dd,J = 8.0,1.4 Hz,1 H,H-6'),6.68 (d,J = 0.6 Hz,1 H,H-7),6.57 (ddd,J = 8.2, 2.4,0.7 Hz,1 H,H-4'),6.49 (s,1 H,6-NH),4.79 (pent,J = 8.8 Hz,1 H,1-CH),3.80 (s,3 H, 3'-OCH 3 ),3.40 (s,3 H,3-CH 3 ),1.95-2.06 (m,4 H,2 × CH 2 ),1.80-1.92 (m,2 H,CH 2 ),1.62-1.72 (m,2 H,CH 2 ); MS m / z 339.2 (MH + ,100%).Anal calcd for C 19 H 22 N 4 O·1 / 2H 2 O: C,65.69; H,6.67; N,16.13. Found: C,65.42; H,6.36; N,15.92%. HPLC purity 99.7%.

[0305] Example 7: SN39240 1-cyclopentyl-6-(2-methoxyphenylamino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (13) [ka] Chloride 6 (110 mg, 0.44 mmol), 2-methoxyaniline (65 mg, 0.52 mmol), Pd 2 dba 3(20 mg, 22 μmol), XPhos (42 mg, 88 μmol), and Cs 2 C.O. 3 A degassed mixture of (285 mg, 0.88 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 13 (135 mg, 91%) as a tan powder. 1 H NMR (CDCl 3 ) δ 7.83-7.90 (m,2 H,H-4,H-6'),7.89-6.98 (m,3 H,H-3',H-4',H-5'),6.83 (s, 1 H,6-NH),6.61 (s,1 H,H-7),4.78 (pent,J = 8.8 Hz,1 H,1-CH),3.90 (s,3 H,2'-OCH 3 ),3.40 (s,3 H,3-CH 3 ),1.98-2.08 (m,4 H,2 × CH 2 ),1.85-1.95 (m,2 H,CH 2 ),1.63-1.75 (m,2 H,CH 2 ); MS m / z 338.4 (MH + ,100%); HRMS calcd for C 19 H 23 N 4 O 2 (MH + ) m / z 339.1816,found 339. 1819 (-1.0 ppm). HPLC purity 99.9%.

[0306] Example 8: SN39241 6-((4-chlorophenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (14) [ka] Chloride 6 (119 mg, 0.47 mmol), 4-chloroaniline (72 mg, 0.57 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (45 mg, 95 μmol), and Cs 2 C.O. 3 A degassed mixture of (308 mg, 0.95 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent evaporated. The residue was purified by chromatography eluting with a gradient (40-60%) of EtOAc / petroleum ether to give imidazopyridinone 14 (80 mg, 49%) as a brown powder. mp (EtOAc / pet ether) 179-181 °C; 1 H NMR (CDCl 3 ) δ 7.83 (s,1 H,H-4),7.22-7.18 (m,4 H,H-2',H-3',H-5',H-6'),6.54 (s,1 H ,H-7),6.43 (s,1 H,6-NH),4.76 (pent,J = 8.8 Hz,1 H,1-CH),3.40 (s,3 H,3-CH 3 ),1.95-2.05 (m,4 H,2 × CH 2 ),1.82-1.92 (m,2 H,CH 2 ),1.63-1.75 (m,2 H,CH 2 ); MS m / z 343.2 (MH + ,100%),345.2 (MH + ,35%).Anal calcd for C 18 H 19 ClN 4 O·0.1EtOAc: C,62.65; H,5.76; N,15.54. Found: C,62.56; H,5.62; N,15.84%. HPLC purity 99.0%.

[0307] Example 9: SN39242 6-((3-chlorophenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (15) [ka] Chloride 6 (132 mg, 0.52 mmol), 3-chloroaniline (80 mg, 0.63 mmol), Pd 2 dba 3 (24 mg, 26 μmol), XPhos (50 mg, 104 μmol), and Cs 2 C.O. 3 A degassed mixture of (339 mg, 1.04 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-75%) of EtOAc / petroleum ether to give imidazopyridinone 15 (110 mg, 62%) as a tan powder. mp (EtOAc / pet ether) 145-147 °C; 1 H NMR (CDCl 3 ) δ 7.86 (d,J = 0.6 Hz,1 H,H-4),7.40 (t,J = 2.1 Hz,1 H,H-2'),7.22 (t,J = 8.0 Hz,1 H,H -5'),7.11 (ddd,J = 8.2,2.1,0.9 Hz,1 H,H-6'),6.95 (ddd,J = 7.9,2.0,1.0 Hz,1 H,H-4'),6.62 (d,J = 0.6 Hz,1 H,H-7),6.51 (s,1 H,6-NH),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.41 (s,3 H,3-CH 3 ),1.97-2.08 (m,4 H,2 × CH 2 ),1.84-1.94 (m,2 H,CH 2 ),1.68-1.76 (m,2 H,CH 2 ); MS m / z 343.2 (MH + ,100%),345.2 (MH + ,35%).Anal calcd for C 18 H 19 ClN 4 O·0.1EtOAc: C,62.85; H,5.68; N,15.93. Found: C,62.73; H,5.54; N,15.94%. HPLC purity 99.9%.

[0308] Example 10: SN39245 6-((2-chlorophenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (16). [ka] Chloride 6 (130 mg, 0.52 mmol), 2-chloroaniline (80 mg, 0.62 mmol), Pd 2 dba 3 (24 mg, 26 μmol), XPhos (50 mg, 104 μmol), and Cs 2 C.O. 3 A degassed mixture of (339 mg, 1.04 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (5-10%) of EtOAc / DCM to give imidazopyridinone 16 (79 mg, 45%) as a brown foam. 1 H NMR (CDCl 3 ) δ 7.90 (dd,J = 8.3,1.5 Hz,1 H,H-6'),7.87 (s,1 H,H-4),7.39 (dd,J = 8.0,1.5 Hz,1 H,H- 3'),7.23 (dt,J = 8.5,1.5 Hz,1 H,H-5'),6.90 (dt,J = 7.9,1.5 Hz,1 H,H-4'),6.74 (br s,1 H,6-NH),6.61 (s,1 H,H-7),4.77 (pent,J = 8.8 Hz,1 H,1-CH),3.41 (s,3 H,3-CH 3 ),1.98-2.08 (m,4 H,2 × CH 2 ),1.86-1.96 (m,2 H,CH 2 ),1.68-1.77 (m,2 H,CH 2 ); MS m / z 343.2 (MH + ,100%),345.2 (MH + ,35%); HRMS calcd for C 18 H 20 ClN 4 O (MH +) m / z 343.1320,found 343.1318 (0.5 ppm). HPLC purity 98.4%.

[0309] Example 11: SN39246 1-Cyclopentyl-3-methyl-6-(4-nitrophenylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (17). [ka] Chloride 6 (131 mg, 0.52 mmol), 4-nitroaniline (86 mg, 0.63 mmol), Pd 2 dba 3 (24 mg, 26 μmol), XPhos (50 mg, 104 μmol), and Cs 2 C.O. 3 A degassed mixture of (339 mg, 1.04 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 17 (127 mg, 69%) as red crystals. mp (EtOAc / petroleum ether) 270-272 °C; 1 H NMR (CDCl 3 ) δ 8.18 (ddd,J = 9.2,3.1,2.1 Hz,2 H,H-3',H-5'),7.94 (s,1 H,H-4),7.46 (ddd,J = 9.2,3.1 ,2.1 Hz,2 H,H-2',H-6'),6.94 (br s,1 H,6-NH),6.64 (d,J = 0.5 Hz,1 H,H-7),4.82 ( pent,J = 8.8 Hz,1 H,1-CH),3.44 (s,3 H,3-CH 3 ),2.02-2.10 (m,4 H,2 × CH 2 ),1.88-1.98 (m,2 H,CH 2 ),1.70-1.80 (m,2 H,CH 2 ); MS m / z 354.2 (MH + ,100%).Anal calcd for C 18 H 19 N 5 O 3 : C,61.18; H,5.42; N,19.82. Found: C,61.29; H,5.29; N,19.94%. HPLC purity 100.0%.

[0310] Example 12: SN39247 1-Cyclopentyl-3-methyl-6-(3-nitrophenyramino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (18) [ka] Chloride 6 (131 mg, 0.52 mmol), 3-nitroaniline (86 mg, 0.63 mmol), Pd 2 dba 3 (24mg, 26μmol), XPhos (50mg, 104μmol), Cs 2 C.O. 3 A degassed mixture of (339 mg, 1.04 mmol) in dioxane (6 mL) was stirred in a sealed tube at .120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-80%) of EtOAc / petroleum ether to give imidazopyridinone 18 (147 mg, 80%) as a yellow powder. mp (EtOAc / pet ether) 184-186 °C; 1 H NMR (CDCl 3 ) δ 8.36 (t,J = 2.2 Hz,1 H,H-2'),7.91 (s,1 H,H-4),7.78 (ddd,J = 8.1,2.1,0.8 Hz,1 H,H- 6'),7.59 (ddd,J = 8.1,2.0,0.8 Hz,1 H,H-4'),7.43 (t,J = 8.1 Hz,1 H,H-5'),6.75 (s,1 H ,6-NH),6.61 (d,J = 0.4 Hz,1 H,H-7),4.83 (pent,J = 8.8 Hz,1 H,1-CH),3.43 (s,3 H,3-CH 3 ),2.00-2.08 (m,4 H,2 × CH 2 ),1.87-1.97 (m,2 H,CH 2 ),1.70-1.78 (m,2 H,CH 2 ); MS m / z 354.2 (MH + ,100%). Anal. calcd for C 18 H 19 N 5 O 3 : C,61.18; H,5.42; N,19.82. Found: C,60.98; H,5.29; N,19.82%. HPLC purity 99.9%.

[0311] Example 13: SN39263 1-cyclopentyl-3-methyl-6-(2-nitrophenylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (19) [ka] Chloride 6 (131 mg, 0.52 mmol), 2-nitroaniline (86 mg, 0.63 mmol), Pd 2 dba 3 (24 mg, 26 μmol), XPhos (50 mg, 104 μmol), and Cs 2 C.O. 3 A degassed mixture of (339 mg, 1.04 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography, eluting with 40% EtOAc / petroleum ether, to give red crystalline imidazopyridinone 19 (161 mg, 88%). 1 H NMR (CDCl 3 ) δ 10.10 (br s,1 H,6-NH),8.42 (dd,J = 8.8,1.2 Hz,1 H,H-3'),8.32 (dd,J = 8.6,1.6 Hz,1 H,H -6'),7.97 (s,1 H,H-4),7.51 (ddd,J = 8.4,7.1,1.4 Hz,1 H,H-5'),6.90 (ddd,J = 8.4,7.1,1.4 Hz,1 H,H-4'),6.68 (s,1 H,H-7),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.45 (s,3 H,3-CH 3 ),1.92-2.10 (m,6 H,3 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ); MS m / z 354.2 (MH + ,100%).Anal calcd for C 18 H 19 N 5 O 3 : C,61.18; H,5.42; N,19.82. Found: C,60.89; H,5.34; N,19.61%. HPLC purity 99.9%.

[0312] Example 14: SN39273 N-(4-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)phenyl)acetamide (20) [ka] Chloride 6 (118 mg, 0.47 mmol), N-(4-aminophenyl)acetamide (85 mg, 0.56 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (45 mg, 94 μmol), and Cs 2 C.O. 3 A degassed mixture of (306 mg, 0.94 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH / EtOAc to give imidazopyridinone 20 (136 mg, 75%) as a milky white powder. mp (EtOAc / pet ether) 152-155 °C; 1 H NMR (CDCl 3) δ 7.80 (s,1 H,H-4''),7.45 (br d,J = 8.8 Hz,2 H,H-2',H-6'),7.20-7.30 (m,3 H,CONH ,H-3',H-5'),6.55 (s,1 H,H-7''),6.43 (s,1 H,4'-NH),4.74 (pent,J = 8.8 Hz,1 H ,1''-CH),3.39 (s,3 H,3''-CH 3 ),2.17 (s,3 H,COCH 3 ),1.95-2.04 (m,4 H,2 × CH 2 ),1.82-1.92 (m,2 H,CH 2 ),1.63-1.73 (m,2 H,CH 2 ); MS m / z 366.2 (MH + ,100%).Anal calcd for C 20 H 23 N 5 O 2 : C,65.73; H,6.34; N,19.16. Found: C,65.88; H,6.44; N,18.81%. HPLC purity 100.0%.

[0313] Example 15: SN39280N-(3-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)phenyl)acetamide( twenty one) [ka] Chloride 6 (110mg, 0.44mmol), N-(3-aminophenyl)acetamide (80mg, 0.53mmol), Pd 2 dba 3 (20 mg, 22 μmol), XPhos (42 mg, 88 μmol), and Cs 2 C.O. 3 A degassed mixture of (289 mg, 0.88 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (0-10% MeOH / EtOAc) to give imidazopyridinone 21 (130 mg, 81%) as tan crystals. mp (EtOAc) 215-217 °C; 1 H NMR (CDCl 3 ) δ 7.83 (s,1 H,H-4'),7.78 (br s,1 H,H-2),7.38 (br s,1 H,CONH),7.22 (t,J = 8.0 Hz,1 H ,H-5),7.04 (br dd,J = 8.0,1.3 Hz,1 H,H-6),6.93 (d,J = 7.9 Hz,1 H,H-4),6.66 (s,1 H, H-7'),6.62 (s,1 H,3-NH),4.78 (pent,J = 8.8 Hz,1 H,1'-CH),3.39 (s,3 H,3'-CH 3 ),2.16 (s,3 H,COCH 3 ),1.98-2.07 (m,4 H,2 × CH 2 ),1.84-1.92 (m,2 H,CH 2 ),1.65-1.74 (m,2 H,CH 2 ); MS m / z 366.2 (MH + ,100%); HRMS calcd for C 20 H 24 N 5 O 2 (MH + ) m / z 366.1925,found 366.1920 (1.3 ppm). HPLC purity 99.3%.

[0314] Example 16: SN39301N-(2-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)phenyl)acetamide( twenty two) [ka] Chloride 6 (133mg, 0.53mmol), N-(2-aminophenyl)acetamide (95mg, 0.63mmol), Pd 2 dba 3 (24 mg, 27 μmol), XPhos (50 mg, 106 μmol), and Cs 2 C.O. 3 A degassed mixture of (345 mg, 1.06 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-5%) of MeOH / EtOAc to give imidazopyridinone 22 (185 mg, 96%) as a tan powder. mp (MeOH / EtOAc) 181-183 °C; 1 H NMR (CDCl 3 ) δ 8.11 (br s,1 H,CONH),7.95 (d,J = 7.4 Hz,1 H,H-6),7.78 (s,1 H,H-4'),7.30 (d,J = 7.2 Hz,1 H,H-3),7.18 (br dd,J = 7.6,6.6 Hz,1 H,H-5),7.13 (br dd,J = 7.7,6.4 Hz,1 H,H-4), 6.39 (br s,1 H,6'-NH),6.18 (s,1 H,H-7'),4.68 (pent,J = 8.7 Hz,1 H,1-CH),3.38 (s,3 H ,3-CH 3 ),2.12 (s,3 H,COCH 3 ),1.89-2.00 (m,4 H,2 × CH 2 ),1.75-1.85 (m,2 H,CH 2 ),1.60-1.68 (m,2 H,CH 2 ); MS m / z 366.2 (MH + ,100%); HRMS calcd for C 20 H 24 N 5 O 2 (MH + ) m / z 365.1852,found 365.1872 (-5.4 ppm). HPLC purity 98.9%.

[0315] Example 17: SN39275 4-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)benzylnitrile (23) [ka] Chloride 6 (122mg, 0.49mmol), 4-aminobenzonitrile (69mg, 0.58mmol), Pd 2 dba 3 (22 mg, 25 μmol), XPhos (47 mg, 98 μmol), and Cs 2 C.O. 3 A degassed mixture of (319 mg, 0.98 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). Organic fraction water 39278 mL), brine (30 mL) and dry (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (60-80% EtOAc / petroleum ether) to give 23 (131 mg, 81%) as a milky white powder. mp (EtOAc / pet ether) 236-238 °C; 1 H NMR (CDCl 3 ) δ 7.91 (s,1 H,H-4'),7.45 (ddd,J = 8.8,2.3,2.0 Hz,2 H,H-3,H-5),7.43 (ddd,J = 8.8,2.3, 2.0 Hz,2 H,H-2,H-6),6.77 (s,1 H,4-NH),6.60 (s,1 H,H-7'),4.81 (pent,J = 8.8 Hz,1 H,1'-CH),3.43 (s,3 H,3'-CH 3 ),1.88-2.09 (m,6 H,3 × CH 2 ),1.68-1.78 (m,2 H,CH 2 ); MS m / z 351.2 (MH + ,100%).Anal calcd for C 19 H 19 N 5 O: C,68.45; H,5.74; N,21.01. Found: C,68.24; H,5.84; N,20.86%. HPLC purity 100.0%.

[0316] Example 18: SN39291 3-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)benzylnitrile (24) [ka] Chloride 6 (122 mg, 0.49 mmol), 3-aminobenzonitrile (69 mg, 0.58 mmol), Pd 2 dba 3 (22 mg, 25 μmol), XPhos (47 mg, 98 μmol), and Cs 2C.O. 3 A degassed mixture of (319 mg, 0.98 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-60%) of EtOAc / petroleum ether to give imidazopyridinone 24 (120 mg, 74%) as a milky white powder. mp (EtOAc / pet ether) 233-235 °C; 1 H NMR (CDCl 3 ) δ 7.88 (s,1 H,H-4),7.85 (t,J = 1.8 Hz,1 H,H-2'),7.50 (ddd,J = 8.3,2.3,1.0 Hz,1 H,H- 6'),7.36 (t,J = 8.0 Hz,1 H,H-5'),7.22 (dt,J = 7.6,1.2 Hz,1 H,H-4'),6.61 (br s,1 H, 6-NH),6.53 (s,1 H,H-7),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.42 (s,3 H,3-CH 3 ),1.98-2.08 (m,4 H,2 × CH 2 ),1.87-1.97 (m,2 H,CH 2 ),1.69-1.79 (m,2 H,CH 2 ); MS m / z 334.2 (MH + ,100%).Anal calcd for C 19 H 19 N5O·0.1EtOAc: C,68.09; H,5.83; N,20.47. Found: C,67.93; H,6.05; N,20.47%. HPLC purity 100.0%.

[0317] Example 19: SN39297 2-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)benzylnitrile (25) [ka] Chloride 6 (120 mg, 0.48 mmol), 2-aminobenzonitrile (68 mg, 0.57 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (313 mg, 0.96 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 25 (101 mg, 64%) as orange crystals, eluting with EtOAc. mp (MeOH / EtOAc) 171-173 °C; 1 H NMR (CDCl 3 ) δ 8.83 (s,1 H,H-4),8.13 (br s,1 H,6-NH),7.90 (dd,J = 8.2,1.0 Hz,1 H,H-6'),7.63 (ddd ,J = 8.3,6.9,1.3 Hz,1 H,H-4'),7.55 (dd,J = 8.3,1.0 Hz,1 H,H-3'),7.30 (ddd,J = 8.2,6.9,1.2 Hz,1 H,H-5'),6.76 (s,1 H,H-7),4.82 (pent,J = 8.8 Hz,1 H,1-CH),3.49 (s,3 H,3-CH 3 ),1.95-2.15 (m,6 H,3 × CH 2 ),1.68-1.80 (m,2 H,CH 2 ); MS m / z 334.2 (MH + ,100%). Anal. calcd for C 19 H 19 N 5 O・1.3CH 3 OH: C, 65.01; H, 6.50; N, 18.67. Found C,64.71; H,6.41; N,18.99%. HPLC purity 98.8%.

[0318] Example 20: SN39278 1-Cyclopentyl-3-methyl-6-((4-(trifluoromethyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 26). [ka] Chloride 6 (111 mg, 0.44 mmol), 4-(trifluoromethyl)aniline (85 mg, 0.53 mmol), Pd 2 dba 3 (20 mg, 22 μmol), XPhos (42 mg, 88 μmol), and Cs 2 C.O. 3 A degassed mixture of (289 mg, 0.88 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (50-70% EtOAc / petroleum ether) to give 26 (125 mg, 75%) as a milky white powder. mp (EtOAc / pet ether) 196-199 °C; 1 H NMR (CDCl 3 ) δ 7.88 (d,J = 0.4 Hz,1 H,H-4),7.53 (d,J = 8.6 Hz,2 H,H-3',H-5'),7.39 (d,J = 8.5 Hz ,2 H,H-2',H-6'),6.66 (br s,1 H,6-NH),6.63 (s,1 H,H-7),4.80 (pent,J = 8.8 Hz,1 H,1-CH),3.42 (s,3 H,3-CH 3 ),1.99-2.07 (m,4 H,2 × CH 2 ),1.87-1.95 (m,2 H,CH 2 ),1.68-1.78 (m,2 H,CH 2 ); 13 C NMR (CDCl 3 ) δ 154.2,149.4,145.0,137.0,126.8 (q,J = 3.8 Hz),125.9 (2),124.7 (q,J = 233.6 Hz),123.7,123.0 (q,J = 32.8 Hz),117.1 (2 ),91.2,53.9,29.1 (2),27.6,25.3 (2); MS m / z 377.2 (MH + ,100%). Anal. calcd for C 19 H 19 F 3 N 4 O: C,60.63; H,5.09; N,14.89. Found: C,60.68; H,5.30; N,15.02%. HPLC purity 99.7%.

[0319] Example 21: SN39290 1-cyclopentyl-3-methyl-6-((3-(trifluoromethyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 27) [ka] Chloride 6 (125mg, 0.50mmol), 3-(trifluoromethyl)aniline (96mg, 0.60mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (326 mg, 1.00 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (40-50% EtOAc / petroleum ether) to give imidazopyridinone 27 (146 mg, 78%) as milky white needles. mp (EtOAc) 162-163 °C; 1 H NMR (CDCl 3 ) δ 7.87 (s,1 H,H-4),7.78 (s,1 H,H-2'),7.40-7.43 (m,2 H,H-5',H-6'),7.21-7.23 (m,1 H,H-4'),6.68 (br s,1 H,6-NH),6.63 (d,J = 0.4 Hz,1 H,H-7),4.83 (pent,J = 8.8 Hz ,1 H,1-CH),3.42 (s,3 H,3-CH 3 ),1.96-2.07 (m,4 H,2 × CH 2 ),1.83-1.92 (m,2 H,CH 2 ),1.68-1.76 (m,2 H,CH 2 ); 13 C NMR (CDCl 3) δ 154.3,149.8,142.4,136.9,131.8 (q,J = 32.1 Hz),130.0,126.1,124.3 (q,J = 272.3),123.5,121.6,118.2 (q,J = 3.8 Hz),114.5 (q ,J = 3.9 Hz),90.4,53.7,29.2 (2),27.6,25.3 (2); MS m / z 377.2 (MH + ,100%); HRMS calcd for C 19 H 20 F 3 N 4 O (MH + ) m / z 377.1584,found 377.1585 (-0.4 ppm). HPLC purity 99.3%.

[0320] Example 22: SN39283 1-Cyclopentyl-3-methyl-6-((2-(trifluoromethyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 28) [ka] Chloride 6 (114 mg, 0.45 mmol), 2-trifluoroaniline (88 mg, 0.54 mmol), Pd 2 dba 3 (21 mg, 23 μmol), XPhos (43 mg, 90 μmol), and Cs 2 C.O. 3 A degassed mixture of (293 mg, 0.90 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (10-50%) of EtOAc / petroleum ether to give imidazopyridinone 28 (110 mg, 65%) as a gray foam. 1 H NMR (CDCl 3 ) δ 7.87 (s,1 H,H-4),7.76 (d,J = 8.3 Hz,1 H,H-3'),7.62 (dd,J = 7.8,0.7 Hz,1 H,H-6' ),7.47 (br dd,J = 8.0,7.6 Hz,1 H,H-4'),7.07 (br dd,J = 7.7,765 Hz,1 H,H-5'),6.63 (br s,1 H,6-NH),6.58 (d,J = 0.5 Hz,1 H,H-7),4.76 (pent,J = 8.8 Hz,1 H,1-CH),3.41 (s,3 H,3- CH 3 ),1.97-2.06 (m,4 H,2 × CH 2 ),1.83-1.93 (m,2 H,CH 2 ),1.62-1.74 (m,2 H,CH 2 ); MS m / z 377.2 (MH + ,100%); HRMS calcd for C 19 H 19 F 3 N 4 O (MH + ) m / z 376.1511,found 376.1535 (6.3 ppm). HPLC purity 99.7%.

[0321] Example 23: SN39274 6-((4-acetylphenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (29) [ka] Chloride 6 (117mg, 0.47mmol), 1-(4-aminophenyl)ethan-1-one (75mg, 0.56mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (45 mg, 94 μmol), and Cs 2 C.O. 3 A degassed mixture of (326 mg, 0.94 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (60-100% EtOAc / petroleum ether) to give imidazopyridinone 29 (131 mg, 80%):mp(EtOAc / petroleum ether) as lemon powder. mp (EtOAc / pet ether) 181-183 °C; 1 H NMR (CDCl 3 ) δ 7.89-7.95 (m,3 H,H-4,H-3',H-5'),7.36 (ddd,J = 8.8,2.6,1.9 Hz,2 H,H-2',H-6 ),6.82 (s,1 H,6-NH),6.69 (d,J = 0.5 Hz,1 H,H-7''),4.81 (pent,J = 8.8 Hz,1 H,1-CH) ,3.43 (s,3H,3-CH 3 ),2.56 (s,3 H,COCH 3 ),2.00-2.08 (m,4 H,2 × CH 2 ),1.87-1.97 (m,2 H,CH 2 ),1.70-1.78 (m,2 H,CH 2 ); MS m / z 351.2 (MH + ,100%).Anal calcd for C 20 H 22 N 4 O 2 ·0.1EtOAc: C,68.21; H,6.40; N,15.60. Found: C,68.09; H,6.52; N,15.37%. HPLC purity 97.9%.

[0322] Example 24: SN39279 6-((3-acetylphenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (30) [ka] Chloride 6 (110mg, 0.44mmol), 1-(3-aminophenyl)ethan-1-one (71mg, 0.53mmol), Pd 2 dba 3 (22 mg, 20 μmol), XPhos (42 mg, 88 μmol), and Cs 2 C.O. 3 A degassed mixture of (287 mg, 0.88 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (50-100% EtOAc / petroleum ether) to give imidazopyridinone 30 (147 mg, 80%) as a milky white powder. mp (EtOAc / pet ether) 125-127 °C; 1 H NMR (CDCl 3 ) δ 7.93 (t,J = 1.9 Hz,1 H,H-2'),7.86 (s,1 H,H-4),7.56 (ddd,J = 7.6,1.4,1.1 Hz,1 H,H- 6'),7.53 (ddd,J = 8.1,2.3,0.9 Hz,1 H,H-4'),7.40 (t,J = 7.8 Hz,1 H,H-5'),6.63 (s,1 H ,H-7),6.61 (br s,1 H,6-NH),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.41 (s,3 H,3-CH 3 ),2.60 (s,3 H,COCH 3 ),1.98-2.07 (m,4 H,2 × CH 2 ),1.83-1.93 (m,2 H,CH 2 ),1.67-1.76 (m,2 H,CH 2 ); MS m / z 351.2 (MH + ,100%). Anal. calcd for C 20 H 22 N 4 O 2 : C,68.55; H,6.33; N,15.99. Found: C,68.54; H,6.52; N,16.03%. HPLC purity 99.6%.

[0323] Example 25: SN39304 1-Cyclopentyl-3-methyl-6-((4-(methylsulfonyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (31 ) [ka] Chloride 6 (125 mg, 0.50 mmol), 4-(methylsulfonyl)aniline (102 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3A degassed mixture of (326 mg, 1.00 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 31 (154 mg, 80%) as milky white needles. mp (EtOAc / pet ether) 161-164 °C; 1 H NMR (CDCl 3 ) δ 7.92 (s,1 H,H-4),7.82 (ddd,J = 8.8,2.6,1.9 Hz,2 H,H-2',H-6'),7.51 (ddd,J = 8.8,2.6 ,1.9 Hz,2 H,H-3',H-5'),6.86 (s,1 H,6-NH),6.63 (d,J = 0.3 Hz,1 H,H-7),4.81 (pent ,J = 8.8 Hz,1 H,1-CH),3.43 (s,3 H,3-CH 3 ),3.04 (s,3 H,SO 2 CH 3 ),2.00-2.08 (m,4 H,2 × CH 2 ),1.88-1.98 (m,2 H,CH 2 ),1.88-1.98 (m,2 H,CH 2 ); MS m / z 387.2 (MH + ,100%). Anal. calcd for C 19 H 22 N 4 O 3 S·1 / 2EtOAc: C, 58.59; H, 6.09; N, 13.01. Found: C,58.86; H,6.30; N,13.20%. HPLC purity 99.9%.

[0324] Example 26: SN39308 1-Cyclopentyl-3-methyl-6-((3-(methylsulfonyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (32 ) [ka] Chloride 6 (112 mg, 0.45 mmol), 3-(methylsulfonyl)aniline, HCl (111 mg, 0.53 mmol), Pd 2 dba 3 (21 mg, 23 μmol), XPhos (43 mg, 90 μmol), and Cs 2 C.O. 3 A degassed mixture of (484 mg, 1.49 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (80-100%) of EtOAc / petroleum ether to give imidazopyridinone 32 (154 mg, 90%) as a white powder. mp (EtOAc / pet ether) 208-211 °C; 1 H NMR (CDCl 3 ) δ 8.00 (d,J = 2.8 Hz,1 H,H-2'),7.89 (s,1 H,H-4),7.61-7.66 (m,1 H,H-5'),7.44-7.49 (m,2 H,H-4',H-6'),6.84 (s,1 H,6-NH),6.60 (d,J = 0.5 Hz,1 H,H-7),4.82 (pent, J = 8.8 Hz,1 H,1-CH),3.42 (s,3 H,3-CH 3 ),3.07 (s,3 H,SO 2 CH 3 ),2.00-2.08 (m,4 H,2 × CH 2 ),1.87-1.97 (m,2 H,CH 2 ),1.68-1.77 (m,2 H,CH 2 ); MS m / z 387.2 (MH + ,100%). Anal. calcd for C 19 H 22 N 4 O 3 S·1 / 2EtOAc: C,58.59; H,6.09; N,13.01. Found: C,58.73; H,6.25; N,13.28%. HPLC purity 99.8%.

[0325] Example 27: SN39330 1-Cyclopentyl-3-methyl-6-((2-(methylsulfonyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (33 ) [ka] Chloride 6 (126 mg, 0.50 mmol), 2-(methylsulfonyl)aniline (103 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-80%) of EtOAc / petroleum ether to give imidazopyridinone 33 (168 mg, 87%) as a white powder. mp (EtOAc / pet. ether) 178-181 °C; 1 H NMR (CDCl 3 ) δ 8.42 (br s,1 H,6-NH),8.11 (dd,J = 8.4,0.7 Hz,1 H,H-3'),7.87-7.92 (m,2 H,H-4,H- 6'),7.53 (ddd,J = 8.6,7.1,1.6 Hz,1 H,H-5'),7.04 (ddd,J = 8.2,7.1,1.0 Hz,1 H,H-4'),6.55 ( d,J = 0.5 Hz,1 H,H-7),4.78 (pent,J = 8.8 Hz,1 H,1-CH),3.43 (s,3 H,3-CH 3 ),3.12 (s,3 H,2’-SO 2 CH 3 ),1.93-2.10 (m,6 H,3 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ); MS m / z 387.2 (MH + ,100%); HRMS calcd for C 19 H 23 N 4 O 3 (MH + ) m / z 387.1485,found 387.1493 (-1.9 ppm). HPLC purity 100.0%.

[0326] Example 28: SN39302 6-((4-(benzyloxy)phenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (34 ) [ka] Chloride 6 (200 mg, 0.80 mmol), 4-(benzyloxy)aniline, HCl (225 mg, 0.95 mmol), PPd 2 dba 3 (37mg, 40μmol), XPhos (76mg, 160μmol), and Cs 2 C.O. 3 A degassed mixture of (860 mg, 2.64 mmol) in dioxane (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-80%) of EtOAc / petroleum ether to give imidazopyridinone 34 (215 mg, 65%) as tan crystals. mp (EtOAc / pet ether) 144-147 °C; 1 H NMR (CDCl 3 ) δ 7.77 (s,1 H,H-4),7.45 (br d,J = 7.2 Hz,2 H,H-2'',H-6''),7.39 (br dd,J = 7.6,7.1 Hz,2 H,H-3'',H-5''),7.33 (br t,J = 7.1 Hz,1 H,H-4''),7.20 (ddd,J = 8.9,3.5,2.2 Hz ,2 H,H-2',H-6'),6.97 (ddd,J = 8.9,3.5,2.2 Hz,2 H,H-3',H-5'),6.42 (d,J = 0.5 Hz ,1 H,H-7),6.29 (s,1 H,6-NH),5.07 (s,2 H,CH 2 O),4.73 (pent,J = 8.8 Hz,1 H,1-CH),3.38 (s,3 H,3-CH 3 ),1.93-2.01 (m,4 H,2 × CH2 ),1.76-1.86 (m,2 H,CH 2 ),1.60-1.70 (m,2 H,CH 2 ); MS m / z 415.2 (MH + ,100%).Anal calcd for C 25 H 26 N 4 O 2 ·1 / 4EtOAc: C,71.54; H,6.47; N,12.83. Found: C,71.26; H,6.44; N,12.72%. HPLC purity 99.9%.

[0327] Example 29: SN39303 6-(3(benzyloxy)phenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (35) [ka] Chloride 6 (203 mg, 0.81 mmol), 3-(benzyloxy)aniline (193 mg, 0.97 mmol), Pd 2 dba 3 (37mg, 40μmol), XPhos (77mg, 162μmol), and Cs 2 C.O. 3 A degassed mixture of (528 mg, 1.62 mmol) in dioxane (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-80%) of EtOAc / petroleum ether to give imidazopyridinone 35 (246 mg, 74%) as white needles. mp (EtOAc / pet ether) 110-112 °C; 1 H NMR (CDCl 3 ) δ 7.85 (d,J = 0.4 Hz,1 H,H-4),7.38-7.46 (m,4 H,H-2'',H-3'',H-5'',H-6' ),7.36 (br tt,J = 7.0,1.5 Hz,1 H,H-4''),7.24 (t,J = 8.1 Hz,1 H,H-5'),7.01 (t,J = 2.2 Hz,1 H,H-2'),6.86 (dd,J = 8.0,1.0 Hz,1 H,H-6'),6.71 (d,J = 0.6 Hz,1 H,H-7),6.65 ( ddd,J = 8.2,2.4,0.7 Hz,1 H,H-4'),6.51 (br s,1 H,6-NH),5.08 (s,2 H,CH 2 O),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.42 (s,3 H,3-CH 3 ),1.99-2.08 (m,4 H,2 × CH 2 ),1.85-1.96 (m,2 H,CH 2 ),1.67-1.77 (m,2 H,CH 2 ); MS m / z 415.2 (MH + ,100%).Anal calcd for C 25 H 26 N 4 O 2 : C,72.44; H,6.32; N,13.52. Found: C,71.16; H,6.36; N,13.19%. HPLC purity 100.0%.

[0328] Example 30: SN39328 6-((2-(benzyloxy)phenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (36 ) [ka] Chloride 6 (164 mg, 0.65 mmol), 2-(benzyloxy)aniline (156 mg, 0.78 mmol), Pd 2 dba 3 (30 mg, 33 μmol), XPhos (63 mg, 130 μmol), and Cs 2 C.O. 3 A degassed mixture of (466 mg, 1.43 mmol) in dioxane (10 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-50%) of EtOAc / petroleum ether to give imidazopyridinone 36 (166 mg, 61%) as a white powder. mp (EtOAc / pet. ether) 170-173 °C; 1 H NMR (CDCl 3 ) δ 7.84-7.88 (m,2 H,H-4,H-6'),7.42-7.46 (m,2 H,H-2'',H-6''),7.32-7.40 (m,3 H,H-3'',H-4'',H-5''),6.94-6.99 (m,2 H,H-3',H-4'),6.87-6.89 (m,1 H, H-5'),6.85 (br s,1 H,6-NH),6.61 (d,J = 0.5 Hz,1 H,H-7),5.15 (s,2 H,CH 2 O),4.77 (pent,J = 8.8 Hz,1 H,1-CH),3.39 (s,3 H,3-CH 3 ),1.97-2.05 (m,4 H,2 × CH 2 ),1.84-1.93 (m,2 H,CH 2 ),1.67-1.75 (m,2 H,CH 2 ); MS m / z 415.2 (MH + ,100%); HRMS calcd for C 25 H 27 N 4 O 2 (MH + ) m / z 415.2129,found 415.2135 (-1.7 ppm). HPLC purity 99.6%.

[0329] Example 31: SN39309 2-(4-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)phenyl)- 2-Methylpropanenitrile (37) [ka] Chloride 6 (126 mg, 0.50 mmol), 2-(4-aminophenyl)-2-methylpropanenitrile (96 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 37 (160 mg, 85%) as a tan powder. mp (MeOH / EtOAc) 144-146 °C; 1 H NMR (CDCl 3 ) δ 7.84 (d,J = 0.5 Hz,1 H,H-4''),7.41 (ddd,J = 8.8,2.7,2.1 Hz,2 H,H-3',H-5'),7.32 ( ddd,J = 8.8,2.7,2.1 Hz,2 H,H-2',H-6'),6.58 (d,J = 0.6 Hz,1 H,H-7''),6.50 (s,1 H ,6''-NH),4.78 (pent,J = 8.8 Hz,1 H,1-CH),3.40 (s,3 H,3''-CH 3 ),1.99-2.07 (m,4 H,2 × CH 2 ),1.86-1.95 (m,2 H,CH 2 ),1.68-1.77 (m,8 H,2-CH 3 ,H-3,CH 2 ) MS m / z 376.2 (MH + ,100%). Anal. calcd for C 19 H 25 N 5 O・1 / 4CH 3 OH: C,69.69; H,6.83; N,18.26. Found: C,69.37; H,6.37; N,18.20%. HPLC purity 99.4%.

[0330] Example 32: SN39385 1-cyclopentyl-6-((2,4-dimethylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (38) [ka] Chloride 6 (128 mg, 0.51 mmol), 2,4-dimethylaniline (74 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (49 mg, 102 μmol), and Cs2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 38 (58 mg, 34%) as a white powder. mp (EtOAc / pet ether) 173-175 °C; 1 H NMR (CDCl 3 ) δ 7.78 (d,J = 0.6 Hz,1 H,H-4),7.24 (d,J = 8.0 Hz,1 H,H-6'),7.08 (s,1 H,H-3'), 7.01 (d,J = 8.0 Hz,1 H,H-5'),6.34 (d,J = 0.6 Hz,1 H,H-7),6.06 (br s,1 H,6-NH),4.70 ( pent,J = 8.8 Hz,1 H,1-CH),3.38 (s,3 H,3-CH 3 ),2.34 (s,3 H,4’-CH 3 ),2.24 (s,3 H,2’-CH 3 ),1.92-1.98 (m,4 H,2 × CH 2 ),1.75-1.85 (m,2 H,CH 2 ),1.58-1.68 (m,2 H,CH 2 ); MS m / z 337.2 (MH + ,100%); HRMS calcd for C 20 H 25 N 4 O (MH + ) m / z 337.2010,found 337.2008 (0.4 ppm). HPLC purity 99.6%.

[0331] Example 33: SN39390 1-cyclopentyl-6-((2,3-dimethylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (39) [ka] Chloride 6 (126 mg, 0.50 mmol), 2,3-dimethylaniline (73 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 39 (47 mg, 28%) as a tan foam. 1 H NMR (CDCl 3 ) δ 7.79 (s,1 H,H-4),7.20 (d,J = 7.9 Hz,1 H,H-6'),7.10 (dd,J = 7.8,7.6 Hz,1 H,H-5' ),6.98 (d,J = 7.4 Hz,1 H,H-4'),6.31 (d,J = 0.4 Hz,1 H,H-7),6.20 (br s,1 H,6-NH), 4.71 (pent,J = 8.8 Hz,1 H,1-CH),3.38 (s,3 H,3-CH 3 ),2.34 (s,3 H,3’-CH 3 ),2.19 (s,3 H,2’-CH 3 ),1.89-1.98 (m,4 H,2 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ),1.58-1.67 (m,2 H,CH 2 ); MS m / z 337.2 (MH + ,100%). HRMS calcd for C 20 H 25 N 4 O (MH + ) m / z 337.2023,found 337.2017 (1.7 ppm). HPLC purity 99.1%.

[0332] Example 34: SN39393 1-Cyclopentyl-6-(3,4-dimethylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (40). [ka] Chloride 6 (129mg, 0.51mmol), 3,4-dimethylaniline (75mg, 0.61mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (49 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 40 (99 mg, 57%) as a brown cube. mp (EtOAc / pet ether) 150-151 °C; 1 H NMR (CDCl 3 ) δ 7.80 (d,J = 0.5 Hz,1 H,H-4),7.08 (d,J = 8.0 Hz,1 H,H-5'),7.04 (d,J = 2.3 Hz,1 H,H -2'),6.99 (dd,J = 8.0,2.3 Hz,1 H,H-6'),6.64 (d,J = 0.7 Hz,1 H,H-7),6.40 (br s,1 H, 6-NH),4.78 (pent,J = 8.8 Hz,1 H,1-CH),3.39 (s,3 H,3-CH 3 ),2.25 (s,3 H,3’-CH 3 ),2.24 (s,3 H,2’-CH 3 ),1.96-2.04 (m,4 H,2 × CH 2 ),1.80-1.90 (m,2 H,CH 2 ),1.64-1.74 (m,2 H,CH 2 ); MS m / z 337.2 (MH + ,100%);. HRMS calcd for C 20 H 25 N 4 O (MH + ) m / z 337.2023,found 337.2017 (1.7 ppm). HPLC purity 99.9%.

[0333] Example 35: SN39378 6-((3-chloro-2-methylphenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 41) [ka] Chloride 6 (127mg, 0.50mmol), 3-chloro-2-methylaniline (86mg, 0.61mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-80%) of EtOAc / petroleum ether to give imidazopyridinone 41 (42 mg, 23%) as milky white needles. mp (EtOAc / pet ether) 173-175 °C; 1 H NMR (CDCl 3 ) δ 7.81 (d,J = 0.4 Hz,1 H,H-4),7.31 (dd,J = 7.5,1.6 Hz,1 H,H-4'),7.09-7.16 (m,2 H,H- 5',H-4'),6.38 (s,1 H,H-7),6.19 (br s,1 H,6-NH),4.74 (pent,J = 8.7 Hz,1 H,1-CH) ,3.39 (s,3H,3-CH 3 ),2.34 (s,3 H,2’-CH 3 ),1.90-2.02 (m,4 H,2 × CH 2 ),1.75-1.83 (m,2 H,CH 2 ),1.63-1.70 (m,2 H,CH 2 ); MS m / z 357.2 (MH + ,100%),359.2 (MH + ,35%); HRMS calcd for C19 H 22 ClN 4 O (MH + ) m / z 357.1477,found 357.1480 (-1.0 ppm). HPLC purity 98.0%.

[0334] Example 36: SN39376 6-((4-chloro-2-methylphenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 42) [ka] Chloride 6 (126 mg, 0.50 mmol), 4-chloro-2-methylaniline (85 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 42 (85 mg, 48%) as a tan foam. 1 H NMR (CDCl 3 ) δ 7.81 (s,1 H,H-4),7.36 (d,J = 8.6 Hz,1 H,H-6'),7.23 (d,J = 2.4 Hz,1 H,H-3'), 7.15 (dd,J = 8.6,2.5 Hz,1 H,H-5'),6.40 (s,1 H,H-7),6.06 (br s,1 H,6-NH),4.73 (pent,J = 8.8 Hz,1 H,1-CH),3.39 (s,3 H,3-CH 3 ),2.26 (s,3 H,2’-CH 3 ),1.93-2.02 (m,4 H,2 × CH 2 ),1.78-1.88 (m,2 H,CH 2 ),1.63-1.72 (m,2 H,CH 2 ); MS m / z 357.2 (MH + ,100%),359.2 (MH + ,35%); HRMS calcd for C 19 H 22 ClN 4 O (MH + ) m / z 357.1477,found 357.1476 (0.1 ppm). HPLC purity 97.5%.

[0335] Example 37: SN39379 6-((5-chloro-2-methylphenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 43) [ka] Chloride 6 (131 mg, 0.52 mmol), 5-chloro-2-methylaniline (88 mg, 0.62 mmol), Pd 2 dba 3 (24 mg, 26 μmol), XPhos (50 mg, 104 μmol), and Cs 2 C.O. 3 A degassed mixture of (373 mg, 1.14 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-80%) of EtOAc / petroleum ether to give imidazopyridinone 43 (73 mg, 39%) as a tan foam. 1 H NMR (CDCl 3 ) δ 7.84 (s,1 H,H-4),7.50 (d,J = 2.1 Hz,1 H,H-6'),7.14 (d,J = 8.1 Hz,1 H,H-3'), 6.94 (dd,J = 8.1,2.1 Hz,1 H,H-4'),6.58 (s,1 H,H-7),6.15 (br s,1 H,6-NH),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.39 (s,3 H,3-CH 3 ),2.54 (s,3 H,2’-CH 3 ),1.83-2.08 (m,6 H,3 × CH 2 ),1.66-1.75 (m,2 H,CH 2 ); MS m / z 357.2 (MH + ,100%),359.2 (MH + ,35%); HRMS calcd for C 19 H 22 ClN 4 O (MH + ) m / z 357.1477,found 357.147180 (1.6 ppm). HPLC purity 98.0%.

[0336] Example 38: SN39396 1-Cyclopentyl-3-methyl-6-((2-methyl-4-(methylsulfonyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2 -on(44) [ka] Chloride 6 (126 mg, 0.50 mmol), 2-methyl-4-(methylsulfonyl)aniline (110 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (70-100%) of EtOAc / petroleum ether to give imidazopyridinone 44 (134 mg, 67%) as a tan powder. mp (EtOAc / pet ether) 201-203 °C; 1 H NMR (CDCl 3 ) δ 7.92 (d,J = 0.6 Hz,1 H,H-4),7.78 (d,J = 8.5 Hz,1 H,H-6'),7.69-7.75 (m,2 H,H-3' ,H-5'),6.70 (d,J = 0.6 Hz,1 H,H-7),6.40 (br s,1 H,6-NH),4.79 (pent,J = 8.8 Hz,1 H,1 -CH),3.44 (s,3H,3-CH 3 ),3.04 (s,3 H,4’-SO 2 CH 3 ),2.37 (s,3 H,2’-CH 3 ),2.00-2.08 (m,4 H,2 × CH 2 ),1.87-1.96 (m,2 H,CH 2 ),1.70-1.78 (m,2 H,CH 2 ); MS m / z 401.2 (MH + ,100%); HRMS calcd for C 20 H 25 N 4 O 3 S (MH + ) m / z 401.1642,found 401.1635 (1.8 ppm). HPLC purity 98.7%.

[0337] Example 39: SN39397 1-Cyclopentyl-3-methyl-6-((2-methyl-5-(methylsulfonyl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2 -On(45). [ka] Chloride 6 (126 mg, 0.50 mmol), 2-methyl-5-(methylsulfonyl)aniline (111 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgS 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (70-100%) of EtOAc / petroleum ether to give imidazopyridinone 45 (156 mg, 78%) as a tan powder. mp (EtOAc / pet ether) 170-172 °C; 1 H NMR (CDCl 3) δ 8.15 (d,J = 1.8 Hz,1 H,H-6'),7.88 (s,1 H,H-4),7.46 (dd,J = 7.8,1.8 Hz,1 H,H-4' ),7.38 (d,J = 7.8 Hz,1 H,H-3'),6.66 (d,J = 0.6 Hz,1 H,H-7),6.26 (br s,1 H,6-NH), 4.82 (pent,J = 8.8 Hz,1 H,1-CH),3.42 (s,3 H,3-CH 3 ),3.02 (s,3 H,5’-SO 2 CH 3 ),2.38 (s,3 H,2’-CH 3 ),1.98-2.07 (m,4 H,2 × CH 2 ),1.84-1.94 (m,2 H,CH 2 ),1.65-1.75 (m,2 H,CH 2 ); MS m / z 401.2 (MH + ,100%); HRMS calcd for C 20 H 25 N 4 O 3 S (MH + ) m / z 401.1642,found 401.1638 (1.0 ppm). HPLC purity 99.7%.

[0338] Example 40: SN39398 4-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)-3-methylbenzylnitrile (46) [ka] Chloride 6 (129mg, 0.51mmol), 4-amino-3-methylbenzonitrile (81mg, 0.61mmol), Pd 2 dba 3 (23mg, 26μmol), XPhos (49mg, 102μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (50-100% EtOAc / petroleum ether) to give nitrile 50 (43 mg, 24%) as tan crystals. 1 H NMR (CDCl 3 ) δ 7.91 (d,J = 0.4 Hz,1 H,H-4'),7.70 (d,J = 8.7 Hz,1 H,H-5),7.43-7.47 (m,2 H,H-2, H-6),6.67 (d,J = 0.4 Hz,1 H,H-7'),6.36 (br s,1 H,4-NH),4.80 (pent,J = 8.8 Hz,1 H,1' -CH),3.43 (s,3 H,3'-CH 3 ),2.32 (s,3 H,3-CH 3 ),1.99-2.08 (m,4 H,2 × CH 2 ),1.86-1.96 (m,2 H,CH 2 ),1.70-1.79 (m,2 H,CH 2 ); MS m / z 348.2 (MH + ,100%); HRMS calcd for C 20 H 22 N 5 O (MH + ) m / z 348.1819,found 348.1812 (2.0 ppm). HPLC purity 99.9%.

[0339] Example 41: SN39401 4-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)-2-methylbenzylnitrile (47) [ka] Chloride 6 (129mg, 0.51mmol), 4-amino-2-methylbenzonitrile (81mg, 0.62mmol), Pd 2 dba 3 (26 mg, 23 μmol), XPhos (49 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (50-60% EtOAc / petroleum ether) to give nitrile 47 (66 mg, 37%) as milky white crystals. 1 H NMR (CDCl 3 ) δ 7.91 (s,1 H,H-4'),7.49 (d,J = 8.5 Hz,1 H,H-6),7.29 (d,J = 2.2 Hz,1 H,H-3),7.20 (dd,J = 8.5,2.2 Hz,1 H,H-5),6.71 (br s,1 H,4-NH),6.63 (s,1 H,H-7'),4.83 (pent,J = 8.7 Hz,1 H,1'-CH),3.42 (s,3 H,3'-CH 3 ),2.50 (s,3 H,2-CH 3 ),1.99-2.09 (m,4 H,2 × CH 2 ),1.86-1.95 (m,2 H,CH 2 ),1.70-1.78 (m,2 H,CH 2 ); MS m / z 348.2 (MH + ,100%); HRMS calcd for C 20 H 22 N 5 O (MH + ) m / z 348.1819,found 348.1812 (2.0 ppm). HPLC purity 100.0%.

[0340] Example 42: SN39369 1-Cyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 48) [ka] Chloride 6 (128 mg, 0.51 mmol), 4-methoxy-2-methylaniline (84 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (49 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (70-100%) of EtOAc / petroleum ether to give imidazopyridinone 48 (84 mg, 47%) as a tan gum. 1 H NMR (CDCl 3 ) δ 7.75 (d,J = 0.4 Hz,1 H,H-4),7.23 (d,J = 8.6 Hz,1 H,H-6'),6.84 (d,J = 2.9 Hz,1 H,H -3'),6.77 (d,J = 8.6,2.9 Hz,1 H,H-5'),6.10 (s,1 H,H-7),5.99 (br s,1 H,6-NH), 4.67 (pent,J = 8.7 Hz,1 H,1-CH),3.82 (s,3 H,4'-OCH 3 ),3.37 (s,3 H,3-CH 3 ),2.50 (s,3 H,2’-CH 3 ),1.87-1.97 (m,4 H,2 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ),1.57-1.67 (m,2 H,CH 2 ); MS m / z 353.2 (MH + ,100%); HRMS HRMS calcd for C 20 H 25 N 4 O 2 (MH + ) m / z 353.1972,found 353.1979 (-2.0 ppm). HPLC purity 99.4%.

[0341] Example 43: SN39382 1-Cyclopentyl-6-((5-methoxy-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 49) [ka] Chloride 6 (128 mg, 0.51 mmol), 5-methoxy-2-methylaniline (84 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 26 μmol), XPhos (41 mg, 102 μmol), and Cs 2 C.O.3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 49 (93 mg, 52%) as a brown foam. 1 H NMR (CDCl 3 ) δ 7.82 (s,1 H,H-4),7.13 (d,J = 8.3 Hz,1 H,H-3'),7.03 (d,J = 2.6 Hz,1 H,H-6'), 6.57 (dd,J = 8.3,2.6 Hz,1 H,H-4'),6.54 (d,J = 0.6 Hz,1 H,H-7),6.15 (br s,1 H,6-NH), 4.76 (pent,J = 8.8 Hz,1 H,1-CH),3.76 (s,3 H,5'-OCH 3 ),3.40 (s,3 H,3-CH 3 ),2.21 (s,3 H,2’-CH 3 ),1.96-2.04 (m,4 H,2 × CH 2 ),1.78-1.88 (m,2 H,CH 2 ),1.62-1.72 (m,2 H,CH 2 ); MS m / z 353.2 (MH + ,100%); HRMS calcd for C 20 H 25 N 4 O 2 (MH + ) m / z 353.1972,found 352.1964 (2.2 ppm). HPLC purity 99.0%.

[0342] Example 44: SN39474 1-cyclopentyl-6-((4-methoxy-2-methylphenyl)(methyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2 -On(50) [ka] NaH (60% dispersion, 13 mg, 0.33 mmol) was added to a stirred solution of imidazopyridinone 44 (105 mg, 0.30 mmol) and MeI (28 μL, 0.45 mmol) in dry DMF (5 mL) at 5 °C. . The mixture was stirred at 20° C. for 16 hours and then quenched with ice / water (2 mL). The mixture was partitioned between EtOAc (50ml) and water (30ml). The organic fraction was washed with water (2 x 30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-80%) of EtOAc / petroleum ether to give imidazopyridinone 50 (69 mg, 66%) as a clear gel. 1 H NMR (CDCl 3 ) δ 7.81 (s,1 H,H-4),7.09 (d,J = 8.5 Hz,1 H,H-6'),6.86 (d,J = 2.9 Hz,1 H,H-3'), 6.82 (d,J = 8.5,2.9 Hz,1 H,H-5'),5.69 (s,1 H,H-7),4.62 (pent,J = 8.6 Hz,1 H,1-CH),3.83 (s,3 H,4'-OCH 3 ),3.36 (s,3 H,6-NCH 3 ),3.34 (s,3 H,3-CH 3 ),2.05 (s,3 H,2’-CH 3 ),1.76-1.90 (m,4 H,2 × CH 2 ),1.50-1.60 (m,4 H,2 × CH 2 ); MS m / z 367.2 (MH + ,100%); HRMS calcd for C 21 H 27 N 4 O 2 (MH + ) m / z 367.2129,found 367.2124 (1.2 ppm). HPLC purity 97.2%.

[0343] Example 45: SN39370 6-((4-(benzyloxy)-2-methylphenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2 -On(51) [ka] Chloride 6 (281 mg, 1.12 mmol), 4-phenoxy-2-methylaniline (286 mg, 1.34 mmol), Pd 2 dba 3 (51 mg, 56 μmol), XPhos (107 mg, 224 μmol), and Cs 2 C.O. 3 A degassed mixture of (803 mg, 2.46 mmol) in dioxane (10 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 51 (219 mg, 46%) as a tan foam. 1 H NMR (CDCl 3 ) δ 7.76 (s,1 H,H-4),7.45 (br d,J = 8.9 Hz,2 H,H-2'',H-6''),7.36-7.43 (m,2 H,H -3'',H-5''),7.33 (br t,J = 7.2 Hz,1 H,H-4''),7.23 (d,J = 8.6 Hz,1 H,H-6'), 6.92 (d,J = 2.9 Hz,1 H,H-3'),6.83 (dd,J = 8.6,2.9 Hz,1 H,H-5'),6.12 (d,J = 0.5 Hz,1 H, H-7),5.98 (br s,1 H,6-NH),5.07 (s,2 H,CH 2 O),4.67 (pent,J = 8.8 Hz,1 H,1-CH),3.37 (s,3 H,3-CH 3 ),2.24 (s,3 H,2’-CH 3 ),1.88-1.97 (m,4 H,2 × CH 2 ),1.68-1.78 (m,2 H,CH 2 ),1.57-1.65 (m,2 H,CH 2 ); MS m / z 429.2 (MH + ,100%); HRMS calcd for C 26 H 29 N 4 O 2 (MH + ) m / z 429.2285,found 429.2292 (-1.6 ppm). HPLC purity 99.0%.

[0344] Example 46: SN39642 1-Cyclopentyl-6-((4-fluoro-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 52) [ka] Chloride 6 (404mg, 1.61mmol), 4-fluoro-2-methylaniline (241mg, 1.93mmol), Pd 2 dba 3 (74 mg, 81 μmol), XPhos (154 mg, 154 μmol), and Cs 2 C.O. 3 A degassed mixture of (1.154 mg, 3.54 mmol) in dioxane (20 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (80 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (80 mL) and water (80 mL). The organic fraction was washed with water (50 mL), brine (50 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 52 (368 mg, 67%) as a tan gum. 1 H NMR (CDCl 3 ) δ 7.77 (d,J = 0.5 Hz,1 H,H-4),7.31 (dd,J = 8.7,5.3 Hz,1 H,H-6'),6.98 (dd,J = 9.2,2.9 Hz, 1 H,H-3'),6.92 (dt,J = 8.4,2.9 Hz,1 H,H-5'),6.19 (d,J = 0.6 Hz,1 H,H-7),6.15 (br s ,1 H,6-NH),4.70 (pent,J = 8.7 Hz,1 H,1-CH),3.38 (s,3 H,3-CH 3 ),2.27 (s,3 H,2’-CH 3 ),1.88-2.00 (m,4 H,2 × CH 2 ),1.73-1.82 (m,2 H,CH 2 ),1.60-1.70 (m,2 H,CH 2 ); MS m / z 341.2 (MH + ,100%). HRMS calcd for C 19 H 22 FN 4 O (MH +) m / z 341.1772,found 341.1776 (-1.1 ppm). HPLC purity 97.9%.

[0345] Example 47: SN39748 1-Cyclopentyl-3-methyl-6-((2-methyl-4-(trifluoromethoxy)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridine- 2-on(53). [ka] Chloride 6 (136 mg, 0.54 mmol), 2-methyl-4-(trifluoromethoxy)aniline (124 mg, 0.65 mmol), Pd 2 dba 3 (25 mg, 27 μmol), XPhos (51 mg, 108 μmol), and Cs 2 C.O. 3 A degassed mixture of (387 mg, 1.19 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (70-100%) of EtOAc / petroleum ether to give imidazopyridinone 53 (96 mg, 44%) as a tan gum. 1 H NMR (CDCl 3 ) δ 7.84 (s,1 H,H-4),7.46 (d,J = 8.7 Hz,1 H,H-6'),7.13 (br s,1 H,H-3'),7.08 (br d ,J = 8.6 Hz,1 H,H-5'),6.40 (d,J = 0.3 Hz,1 H,H-7),6.10 (br s,1 H,6-NH),4.77 (pent,J = 8.8 Hz,1 H,1-CH),3.41 (s,3 H,3-CH 3 ),2.31 (s,3 H,2’-CH 3 ),1.94-2.04 (m,4 H,2 × CH 2 ),1.78-1.87 (m,2 H,CH 2 ),1.66-1.76 (m,2 H,CH 2 ); MS m / z 407.2 (MH + ,100%). HRMS calcd for C 20 H 22 F 3 N 4 O 2 (MH + ) m / z 407.1689,found 407.1692 (-0.5 ppm). HPLC purity 98.2%.

[0346] Example 48: SN3976 1-cyclopentyl-6-((4-(difluoromethoxy)-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2 -On(54) [ka] Chloride 6 (136 mg, 0.54 mmol), 4-(difluoromethoxy)-2-methylaniline, HCl (136 mg, 0.65 mmol), Pd 2 dba 3 (25 mg, 27 μmol), XPhos (52 mg, 108 μmol), and Cs 2 C.O. 3 A degassed mixture of (563 mg, 1.73 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (70-100%) of EtOAc / petroleum ether to give imidazopyridinone 54 (105 mg, 50%) as a tan gum. 1 H NMR (CDCl 3 ) δ 7.80 (s,1 H,H-4),7.39 (d,J = 8.7 Hz,1 H,H-6'),7.03 (d,J = 2.7 Hz,1 H,H-3'), 6.98 (dd,J = 8.7,2.7 Hz,1 H,H-5'),6.48 (t,J = 74.2 Hz,1 H,4'-OCHF 2 ),6.33 (d,J = 0.6 Hz,1 H,H-7),6.07 (br s,1 H,6-NH),4.73 (pent,J = 8.7 Hz,1 H,1-CH),3.39 (s,3 H,3-CH 3 ),2.28 (s,3 H,2’-CH 3 ),1.98-2.04 (m,4 H,2 × CH 2 ),1.73-1.84 (m,2 H,CH 2 ),1.62-1.70 (m,2 H,CH 2 ); MS m / z 389.2 (MH + ,100%). HRMS calcd for C 20 H 23 F 2 N 4 O 2 (MH + ) m / z 389.1784,found 389.1783 (0.1 ppm). HPLC purity 99.9%.

[0347] Example 49: SN39764 1-Cyclopentyl-6-((4-ethoxy-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 55) [ka] 4-Ethoxy-2-methyl-1-nitrobenzene: 3-methyl-4-nitrophenol (1.00 g, 6.5 mmol) and K in methyl ethyl ketone (50 ml) 2 C.O. 3 Diethyl sulfate (0.94 mL, 7.2 mmol) was added to a stirred suspension of (2.26 g, 16.3 mmol), and the mixture was stirred at 70° C. for 4 hours. Cool the mixture to 20 °C and dilute with cNH 4 OHOH solution (2 mL) was added and the mixture was stirred at 20° C. for 16 hours. The mixture was partitioned between EtOAc (100ml) and water (100ml). The organic fraction was washed with water (2 x 50 mL), brine (50 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (5-10%) of EtOAc / petroleum ether to give nitrobenzene (1.14 g, 96%) as a white solid: mp 50-51 °C (lit. 1 mp 50-52 °C); 1 H NMR (CDCl 3 ) δ 8.08 (d,J = 8.6 Hz,1 H,H-6),6.76-6.80 (m,2 H,H-3,H-5),4.10 (q,J = 7.0 Hz,2 H,CH 2 O),2.63 (s,3 H,2-CH 3 ),1.45 (t,J = 7.0 Hz,3 H,CH 3 ); MS m / z 182.2 (MH + ,100%). 4-Ethoxy-2-methylaniline: A mixture of nitrobenzene (413 mg, 2.3 mmol) and Pd / C (5%, 50 mg) in EtOH (100 mL) was purified with H 2 The mixture was stirred vigorously for 6 hours. The mixture was filtered through a mat washed with diatomaceous earth, EtOH (10 mL). Evaporation of the solvent gave aniline (329 mg, 95%) as a clear oil. 1 H NMR (CDCl 3 ) δ 6.35-6.68 (m,1 H,H-6),6.60-6.62 (m,2 H,H-3,H-5),3.95 (q,J = 7.0 Hz,2 H,CH 2 O),3.34 (br s,2 H,NH 2 ),2.16 (s,3 H,2-CH 3 ),1.36 (t,J = 7.0 Hz,3 H,CH 3 ); MS m / z 152.2 (MH + ,100%). 1-Cyclopentyl-6-((4-ethoxy-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (55): Chloride Product 6 (127 mg, 0.50 mmol), 4-ethoxy-2-methylaniline (92 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 55 (123 mg, 67%) as a tan foam. mp 192-194 °C; 1 H NMR (CDCl 3) δ 7.75 (d,J = 0.3 Hz,1 H,H-4),7.21 (d,J = 8.6 Hz,1 H,H-6'),6.83 (d,J = 2.9 Hz,1 H,H -3'),6.76 (dd,J = 8.6,2.9 Hz,1 H,H-5'),6.10 (d,J = 0.5 Hz,1 H,H-7),5.99 (br s,1 H, 6-NH),4.67 (p,J = 8.7 Hz,1 H,1-CH),4.04 (q,J = 7.0 Hz,2 H,4'-OCH 2 ),3.37 (s,3 H,3-CH 3 ),2.24 (s,3 H,2’-CH 3 ),1.90-1.96 (m,4 H,2 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ),1.57-1.66 (m,2 H,CH 2 ),1.42 (t,J = 7.0 Hz,3 H,CH 3 ); MS m / z 367.2 (MH + ,100%). HRMS calcd for C 21 H 27 N 4 O 2 (MH + ) m / z 367.2129,found 367.2141 (-3.5 ppm). HPLC purity 98.2%.

[0348] Example 50: SN39673 1-cyclopentyl-6-((4-((2-(dimethylamino)ethyl)amino)-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4 ,5-c]pyridin-2-one(56) [ka] N,N-dimethyl-2-(3-methyl-4-nitrophenoxy)ethane-1-amine: 4-fluoro-2-methyl-1-nitrobenzene (2.00g, 12.9mmol), K 2 C.O. 3 (5.35g, 38.7mmol) and 2-(dimethylamino)ethan-1-ol (1.61g, 18.1mmol) in DMF (30ml) was stirred at 60°C for 16 hours. The mixture was partitioned between EtOAc (200 mL) and water (100 mL). The organic fraction was washed with water (3 x 100 mL), brine (50 mL) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-5%) of MeOH / DCM to give the amine (0.58 g, 20%) as a red oil. 1 H NMR (CDCl 3 ) δ 8.07 (dd,J = 7.8,1.7 Hz,1 H,H-6'),6.79-6.83 (m,2 H,H-2',H-5'),4.13 (br t,J = 5.6 Hz,2 H,H-2),2.76 (br t,J = 5.6 Hz,2 H,H-1),2.62 (s,3 H,3'-CH 3 ),2.36 [s,6 H,N(CH 3 ) 2 ]; MS m / z 225.1 (MH + ,100%). 4-(2-(dimethylamino)ethoxy)-2-methylaniline: A mixture of nitroaniline (0.58 g, 2.59 mmol) and Pd / C (100 mg) in EtOH (100 mL) and EtOAc (100 mL) was diluted with H 2 (60psi) for 4 hours. The mixture was filtered through a diatomaceous earth mat, washed with EtOH (50ml) and the solvent was evaporated to give aniline (0.44g, 87%) as a beige solid. 1 H NMR [(CD 3 ) 2 SO] δ 6.56 (d,J = 1.2 Hz,1 H,H-3),6.48-6.53 (m,2 H,H-5,H-6),4.35 (br s,2 H,1-NH 2 ),3.84 (br t,J = 6.0 Hz,2 H,H-1’),2.53 (br t,J = 6.0 Hz,2 H,H-2’),2.18 [s,6 H,N(CH 3 ) 2 ],2.02 (s,3 H,2-CH 3 ); MS m / z 195.1 (MH + ,100%). 1-Cyclopentyl-6-((4-((2-(dimethylamino)ethyl)amino)-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c ]Pyridin-2-one (56): Chloride 6 (148 mg, 0.59 mmol), 4-(2-(dimethylamino)ethoxy)-2-methylaniline (91 mg, 0.47 mmol), Pd 2 dba 3 (27 mg, 30 μmol), XPhos (56 mg, 118 μmol), and Cs 2 C.O. 3 A degassed mixture of (432 mg, 1.30 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH / DCM to give imidazopyridinone 56 (80 mg, 33%) as a tan powder. 1 H NMR (CDCl 3 ) δ 7.74 (s,1 H,H-4),7.23 (d,J = 8.6 Hz,1 H,H-6'),6.86 (d,J = 2.9 Hz,1 H,H-3'), 6.78 (d,J = 8.6,2.9 Hz,1 H,H-5'),6.16 (br s,1 H,6-NH),6.10 (s,1 H,H-7),4.67 (pent,J = 8.7 Hz,1 H,1-CH),4.10 (br t,J = 5.6 Hz,2 H,CH 2 O),3.37 (s,3 H,3-CH 3 ),2.80 (br t,J = 5.6,2 H,CH 2 N),2.40 [s,6 H,N(CH 3 ) 2 ],2.14 (s,3 H,2’-CH 3 ),1.90-1.98 (m,4 H,2 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ),1.60-1.66 (m,2 H,CH 2 ); MS m / z 410.2 (MH + ,100%). HRMS calcd for C 23 H 32 N 5 O 2 (MH + ) m / z 410.2551,found 410.2557 (-1.7 ppm). HPLC purity 97.4%.

[0349] Example 51: SN39663 1-Cyclopentyl-3-methyl-6-((2-methyl-4-morpholinophenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 57) [ka] 4-(3-Methyl-4-nitrophenyl)morpholine: 4-fluoro-2-methyl-1-nitrobenzene (1.92g, 12.4mmol)K 2 C.O. 3 A mixture of (2.05g, 14.9mmol) and morpholine (2.16g, 24.8mmol) was stirred in DMF (20ml) at 60°C for 72 hours. The mixture was partitioned between EtOAc (200 mL) and water (100 mL). The organic fraction was washed with water (3 x 100 mL), brine (50 mL) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography to give the morpholide (2.40 g, 87%) as a yellow needle, eluting with 20% EtOAc / petroleum ether. mp 140-142 °C; 1 H NMR (CDCl 3 ) δ 8.09 (d,J = 9.2 Hz,1 H,H-5'),6.71 (dd,J = 9.2,2.9 Hz,1 H,H-6'),6.65 (d,J = 2.9 Hz,1 H,H-2'),3.86 (br dd,J = 5.0,4.9 Hz,4 H,H-2,H-6),3.34 (br dd,J = 5.0,4.9 Hz,4 H,H-3 ,H-5),2.64 (s,3 H,3'-CH 3 ); MS m / z 223.1 (MH + ,100%). 2-Methyl-4-morpholinoaniline: A mixture of nitroaniline (1.30 g, 5.85 mmol) and Pd / C (100 mg) in EtOH (100 mL) and EtOAc (100 mL) was diluted with H 2 The mixture was stirred for 4 hours. The mixture was filtered through a diatomaceous earth mat, washed with EtOH (50 mL) and the solvent was evaporated to give aniline (1.12 g, 99%) as a beige solid. mp 84-86 °C; 1 H NMR (CDCl 3 ) δ 6.71 (d,J = 2.6 Hz,1 H,H-3),6.67 (dd,J = 8.4,2.6 Hz,1 H,H-5),6.63 (d,J = 8.4 Hz,1 H, H-6),3.84 (br dd,J = 4.8,4.7 Hz,4 H,H-2',H-6'),3.38 (br s,2 H,NH 2),3.34 (br dd,J = 4.8,4.7 Hz,4 H,H-3’,H-5’),2.64 (s,3 H,3-CH 3 ); MS m / z 223.1 (MH + ,100%). 1-Cyclopentyl-3-methyl-6-((2-methyl-4-morpholinophenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (57): Chloride Product 6 (133 mg, 0.53 mmol), 2-methyl-4-morpholinoaniline (122 mg, 0.63 mmol), Pd 2 dba 3 (24 mg, 27 μmol), XPhos (51 mg, 106 μmol), and Cs 2 C.O. 3 The degassed mixture of 100 ml of chloride in MeCN (6 mL) was stirred in a sealed tube at 120° C. for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (70-100%) of EtOAc / petroleum ether to give imidazopyridinone 57 (110 mg, 51%) as a tan powder. 1 H NMR (CDCl 3 ) δ 7.75 (d,J = 0.5 Hz,1 H,H-4),7.23 (d,J = 8.6 Hz,1 H,H-6'),6.84 (d,J = 2.8 Hz,1 H,H -3'),6.78 (d,J = 8.6,2.9 Hz,1 H,H-5'),6.15 (d,J = 0.6 Hz,1 H,H-7),6.07 (br s,1 H, 6-NH),4.66 (pent,J = 8.7 Hz,1 H,1-CH),3.88 (br dd,J = 4.9,4.7 Hz,4 H,H-2'',H-6''), 3.47 (s,3H,3-CH 3 ),3.14 (br dd,J = 4.9,4.7 Hz,4 H,H-3'',H-5''),2.25 (s,3 H,2'-CH 3 ),1.90-1.98 (m,4 H,2 × CH 2 ),1.72-1.82 (m,2 H,CH 2 ),1.55-1.65 (m,2 H,CH 2 ); MS m / z 408.2 (MH + ,100%). HRMS HRMS calcd for C 23 H 30 N 5 O 2 (MH + ) m / z 408.2394,found 408.2396 (-0.4 ppm). HPLC purity 98.1%.

[0350] Example 52: SN39637 1-cyclopentyl-3-methyl-6-((2-methyl-4-(4-methylpiperazin-1-yl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5 -c]pyridin-2-one (58). [ka] 1-Methyl-4-(3-methyl-4-nitrophenyl)piperazine: 4-fluoro-2-methyl-1-nitrobenzene (2.28g, 14.7mmol), K 2 C.O. 3 (4.06g, 29.4mmol) and 1-methylpiperazine (2.20g, 22.1mmol) was stirred in DMF (50ml) at 80°C for 16 hours. The mixture was partitioned between EtOAc (200 mL) and water (100 mL). The organic fraction was washed with water (3 x 100 mL), brine (50 mL) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-5%) of MeH / DCM to give piperazine (3.22 g, 93%) as yellow flakes. mp 63-65 °C; 1 H NMR (CDCl 3 ) δ 8.08 (d,J = 9.3 Hz,1 H,H-5'),6.70 (dd,J = 9.3,2.8 Hz,1 H,H-6'),6.64 (d,J = 2.8 Hz,1 H,H-2'),3.04 (br dd,J = 5.2,5.1 Hz,4 H,H-3,H-5),2.63 (s,3 H,1-CH 3 ),2.55 (br dd,J = 5.2,5.1 Hz,4 H,H-2,H-6),2.35 (s,3 H,3’-CH 3 ); MS m / z 236.1 (MH + ,100%). 2-Methyl-4-(4-methylpiperazin-1-yl)aniline: Nitroaniline (0.42 g, 1.79 mmol) and Pd / C (50 mg) were mixed in EtOH (50 mL) and EtOAc (50 mL). H 2 (50psi) for 4 hours. The mixture was filtered through a diatomaceous earth mat, washed with EtOH (50 mL) and the solvent was evaporated to give aniline (0.35 g, 96%) as a white solid. mp 100-102 °C; 1 H NMR (CDCl 3 ) δ 6.73 (d,J = 2.7 Hz,1 H,H-3),6.69 (dd,J = 8.4,2.7 Hz,1 H,H-5),6.62 (d,J = 8.4 Hz,1 H, H-6),3.37 (br s,2 H,NH 2 ),3.07 (br dd,J = 5.0,4.9 Hz,4 H,H-3',H-5'),2.57 (br dd,J = 5.0,4.9 Hz,4 H,H-2',H- 6'),2.34 (s,3 H,4'-CH 3 ),2.16 (s,3 H,3-CH 3 ); MS m / z 206.1 (MH + ,100%). 1-Cyclopentyl-3-methyl-6-((2-methyl-4-(4-methylpiperazin-1-yl)phenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridine -2-one (58): chloride 6 (136 mg, 0.54 mmol), 2-methyl-4-(4-methylpiperazin-1-yl)aniline (133 mg, 0.65 mmol), Pd 2 dba 3 (25 mg, 27 μmol), XPhos (51 mg, 108 μmol), and Cs 2 C.O. 3 A degassed mixture of (387 mg, 1.19 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-5%) of MeOH / DCM to give imidazopyridinone 58 (167 mg, 67%) as a tan gum. 1 H NMR (CDCl 3 ) δ 7.75 (s,1 H,H-4),7.21 (d,J = 8.6 Hz,1 H,H-6'),6.86 (d,J = 2.7 Hz,1 H,H-3'), 6.80 (d,J = 8.6,2.7 Hz,1 H,H-5'),6.13 (d,J = 0.5 Hz,1 H,H-7),6.02 (br s,1 H,6-NH), 4.65 (pent,J = 8.7 Hz,1 H,1-CH),3.37 (s,3 H,3-CH 3 ),3.21 (br dd,J = 5.1,4.9 Hz,4 H,H-3'',H-5''),2.61 (br dd,J = 5.1,4.9 Hz,4 H,H-2'' ,H-6''),2.37 (s,3 H,4'-CH 3 ),2.23 (s,3 H,2’-CH 3 ),1.89-1.97 (m,4 H,2 × CH 2 ),1.71-1.80 (m,2 H,CH 2 ),1.57-1.67 (m,2 H,CH 2 ); MS m / z 421.2 (MH + ,100%); HRMS calcd for C 24 H 33 N 6 O (MH + ) m / z 421.2710,found 421.2718 (-1.7 ppm). HPLC purity 99.2%.

[0351] Example 53: SN39758 1-Cyclopentyl-6-((4-methoxy-2-(trifluoromethyl)phenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine- 2-on(59) [ka] Chloride 6 (137mg, 0.54mmol), 4-methoxy-2-(trifluoromethyl)aniline (124mg, 0.65mmol), Pd 2 dba 3 (25 mg, 27 μmol), XPhos (51 mg, 108 μmol), and Cs 2 C.O. 3 A degassed mixture of (387 mg, 1.19 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 59 (101 mg, 46%) as a tan gum. 1 H NMR (CDCl 3 ) δ 7.80 (s,1 H,H-4),7.58 (d,J = 8.9 Hz,1 H,H-6'),7.18 (d,J = 2.9 Hz,1 H,H-3'), 7.06 (dd,J = 8.9,2.9 Hz,1 H,H-5'),6.34 (s,1 H,H-7),6.31 (br s,1 H,6-NH),4.71 (pent,J = 8.8 Hz,1 H,1-CH),3.85 (s,3 H,4'-OCH 3 ),3.38 (s,3 H,3-CH 3 ),1.94-2.02 (m,4 H,2 × CH 2 ),1.78-1.88 (m,2 H,CH 2 ),1.63-1.72 (m,2 H,CH 2 ); MS m / z 407.2 (MH + ,100%). HRMS calcd for C 20 H 22 F 3 N 4 O 2 (MH + ) m / z 407.1689,found 407.1689 (0.1 ppm). HPLC purity 99.6%.

[0352] Example 54: SN39762 2-((1-cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-6-yl)amino)-5-methoxybenzylnitrile (60) [ka] Chloride 6 (128 mg, 0.51 mmol), 2-amino-5-methoxybenzonitrile (90 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 26 μmol), XPhos (49 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 60 (85 mg, 46%) as a yellow powder. mp (EtOAc / pet ether) 197-200 °C; 1 H NMR [(CD 3 ) 2 SO] δ 9.16 (br s,1 H,6'-NH),8.81 (s,1 H,H-4'),7.92 (d,J = 2.8 Hz,1 H,H-3),7.38 (d ,J = 8.9 Hz,1 H,H-6),7.25 (dd,J = 8.9,2.8 Hz,1 H,H-5),6.75 (s,1 H,H-7'),4.72 (pent, J = 8.5 Hz,1 H,1'-CH),3.87 (s,3 H,4-OCH 3 ),3.30 (s,3 H,3’-CH 3 ),2.00-2.08 (m,4 H,2 × CH 2 ),1.86-1.95 (m,2 H,CH 2 ),1.60-1.70 (m,2 H,CH 2 ); MS m / z 364.2 (MH + ,100%). HRMS calcd for C 20 H 22 N 5 O 2 (MH + ) m / z 364.1768,found 364.1766 (0.5 ppm). HPLC purity 98.8%.

[0353] Example 55: SN39759 6-((2-chloro-4-methoxyphenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 61) [ka] Chloride 6 (130mg, 0.52mmol), 2-chloro-4-methoxyaniline (98mg, 0.62mmol), Pd 2 dba 3 (24 mg, 26 μmol), XPhos (50 mg, 104 μmol), and Cs 2 C.O. 3 A degassed mixture of (373 mg, 1.14 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 61 (108 mg, 56%) as a gray foam, eluting with 50% EtOAc / petroleum ether. 1 H NMR (CDCl 3 ) δ 7.82 (d,J = 0.3 Hz,1 H,H-4),7.67 (d,J = 9.0 Hz,1 H,H-6'),7.00 (d,J = 2.9 Hz,1 H,H -3'),6.83 (dd,J = 9.0,2.9 Hz,1 H,H-5'),6.40 (br s,2 H,6-NH,H-7),4.75 (p,J = 8.8 Hz ,1 H,1-CH),3.81 (s,3 H,4'-OCH 3 ),3.39 (s,3 H,3-CH 3 ),1.95-2.05 (m,4 H,2 × CH 2 ),1.81-1.91 (m,2 H,CH 2 ),1.64-1.72 (m,2 H,CH 2 ); MS m / z 373.2 (MH + ,100%). HRMS calcd for C 19 H 22 35 ClN 4 O 2 (MH + ) m / z 373.1426,found 373.1426 (-0.5 ppm); calcd for C 19 H 22 37 ClN 4 O 2 (MH + ) m / z 375.1403,found 375.1407 (-1.0 ppm). HPLC purity 99.3%.

[0354] Example 56: SN39717 1-Cyclopentyl-6-((2,4-dimethoxyphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (62) [ka] Chloride 6 (1330mg, 0.532mmol), 2,4-dimethoxyaniline (97mg, 0.63mmol), Pd 2 dba 3 (24 mg, 27 μmol), XPhos (51 mg, 106 μmol), and Cs 2 C.O. 3 A degassed mixture of (380 mg, 1.17 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (80-100%) of EtOAc / petroleum ether to give imidazopyridinone 62 (162 mg, 83%) as a pink foam. 1 H NMR (CDCl 3 ) δ 7.80 (d,J = 0.5 Hz,1 H,H-4),7.64 (d,J = 8.7 Hz,1 H,H-6'),6.55 (d,J = 2.7 Hz,1 H,H -3'),6.50 (dd,J = 8.7,2.7 Hz,1 H,H-5'),6.46 (br s,1 H,6-NH),6.43 (d,J = 0.6 Hz,1 H, H-7),4.76 (p,J = 8.8 Hz,1 H,1-CH),3.85 (s,3 H,2'-OCH 3 ),3.82 (s,3 H,4’-OCH 3 ),3.54 (s,3 H,3-CH 3 ),1.96-2.03 (m,4 H,2 × CH 2 ),1.81-1.91 (m,2 H,CH 2 ),1.64-1.72 (m,2 H,CH 2 ); MS m / z 369.2 (MH + ,100%). HRMS calcd for C 20 H 25 N 4 O 3 (MH +) m / z 369.1921,found 369.1926 (-0.2 ppm). HPLC purity 99.6%.

[0355] Example 57: SN39313 1-Cyclopentyl-3-methyl-6-(quinolin-6-ylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (63) [ka] Chloride 6 (121 mg, 0.48 mmol), Quinoline-6-amine (83 mg, 0.58 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (344 mg, 1.06 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 63 (126 mg, 73%) as a yellow powder. mp (EtOAc / pet ether) 260-263 °C; 1 H NMR (CDCl 3 ) δ 8.76 (dd,J = 4.2,1.6 Hz,1 H,H-2'),7.98-8.05 (m,2 H,H-4',H-8'),7.92 (s,1 H,H -4),7.87 (d,J = 2.5 Hz,1 H,H-5'),7.56 (dd,J = 9.1,2.5 Hz,1 H,H-7'),7.34 (dd,J = 8.3, 4.2 Hz,1 H,H-3'),6.81 (br s,1 H,6-NH),6.72 (s,1 H,H-7),4.82 (pent,J = 8.8 Hz,1 H,1 -CH),3.43 (s,3H,3-CH 3 ),1.97-2.08 (m,4 H,2 × CH 2 ),1.82-1.92 (m,2 H,CH 2 ),1.65-1.75 (m,2 H,CH 2 ); MS m / z 360.2 (MH + ,100%).Anal calcd for C 21 H 21 N 5 O·1 / 4H 2 O: C,69.31; H,5.95; N,19.24. Found: C,69.06; H,5.62; N,19.38%. HPLC purity 100.0%.

[0356] Example 58: SN39316 1-Cyclopentyl-3-methyl-6-(quinolin-3-ylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (64) [ka] Chloride 6 (126 mg, 0.50 mmol), Quinoline-3-amine (87 mg, 0.60 mmol), Pd 2 dba 3 (24 mg, 25 μmol), XPhos (47 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 64 (143 mg, 79%) as a tan powder, eluting with EtOAc. mp (EtOAc / pet ether) 207-210 °C; 1 H NMR (CDCl 3 ) δ 8.80 (d,J = 2.7 Hz,1 H,H-2'),8.40 (d,J = 2.6 Hz,1 H,H-4'),8.02 (d,J = 8.2 Hz,1 H, H-5'),7.92 (s,1 H,H-4),7.72 (dd,J = 8.3,1.5 Hz,1 H,H-8'),7.56 (dd,J = 8.3,1.5 Hz,1 H,H-7'),7.50 (ddd,J = 8.2,6.9,1.3 Hz,1 H,H-6'),6.83 (br s,1 H,6-NH),6.62 (d,J = 0.5 Hz,1 H,H-7),4.80 (pent,J = 8.8 Hz,1 H,1-CH),3.43 (s,3 H,3-CH 3 ),1.98-2.08 (m,4 H,2 × CH 2 ),1.84-1.94 (m,2 H,CH 2 ),1.66-1.76 (m,2 H,CH 2 ); MS m / z 360.2 (MH + ,100%); HRMS calcd for C 21 H 22 N 5 O (MH + ) m / z 360.1819,found 360.1822 (-0.9 ppm). HPLC purity 99.9%.

[0357] Example 59: SN39322 1-Cyclopentyl-3-methyl-6-(quinolin-5-ylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (65) [ka] Chloride 6 (120 mg, 0.48 mmol), Quinoline-5-amine (83 mg, 0.57 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (344 mg, 1.06 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 65 (94 mg, 55%) as tan crystals, eluting with EtOAc. mp (EtOAc / pet ether) 150-152 °C; 1 H NMR (CDCl 3 ) δ 8.95 (dd,J = 4.2,1.6 Hz,1 H,H-2'),8.40 (ddd,J = 8.5,1.4,0.8 Hz,1 H,H-4'),7.94 (d,J = 8.5 Hz,1 H,H-6'),7.82 (s,1 H,H-4),7.71 (dd,J = 8.4,7.6 Hz,1 H,H-7'),7.57 (d,J = 7.4 Hz,1 H,H-8'),7.40 (dd,J = 8.5,4.2 Hz,1 H,H-3'),6.85 (br s,1 H,6-NH),6.36 (s,1 H,H-7),4.68 (pent,J = 8.8 Hz,1 H,1-CH),3.40 (s,3 H,3-CH 3 ),1.79-1.96 (m,4 H,2 × CH 2 ),1.52-1.63 (m,4 H,2 × CH 2 ); MS m / z 360.2 (MH + ,100%); HRMS calcd for C 21 H 22 N 5 O (MH + ) m / z 360.1819,found 360.1824 (-1.3 ppm). HPLC purity 99.8%.

[0358] Example 60: SN39323 1-Cyclopentyl-6-(isoquinolin-5-ylamino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (66) [ka] Chloride 6 (120 mg, 0.48 mmol), Isoquinoline-5-amine (83 mg, 0.57 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (344 mg, 1.06 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 66 (73 mg, 43%) as a milky white powder, eluting with EtOAc. mp (EtOAc / MeOH) 234-237 °C; 1 H NMR (CDCl 3) δ 9.28 (d,J = 0.6 Hz,1 H,H-1'),8.53 (d,J = 6.0 Hz,1 H,H-3'),7.86 (s,1 H,H-4), 7.73-7.82 (m,3 H,H-4',H-6',H-8'),7.58 (dd,J = 7.9,7.8 Hz,1 H,H-7'),6.83 (br s, 1 H,6-NH),6.44 (d,J = 0.6 Hz,1 H,H-7),4.74 (pent,J = 8.8 Hz,1 H,1-CH),3.41 (s,3 H,3 -CH 3 ),1.83-1.99 (m,4 H,2 × CH 2 ),1.54-1.67 (m,4 H,2 × CH 2 ); MS m / z 360.2 (MH + ,100%); HRMS calcd for C 21 H 22 N 5 O (MH + ) m / z 360.1819,found 360.1822 (-0.9 ppm). HPLC purity 93.6%.

[0359] Example 61: SN39325 1-Cyclopentyl-3-methyl-6-((2-methylquinolin-4-yl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 67) [ka] Chloride 6 (128 mg, 0.51 mmol), 2-methylquinolin-4-amine (97 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 26 μmol), XPhos (48 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH / EtOAc to give imidazopyridinone 67 (134 mg, 71%) as tan crystals. mp (EtOAc / MeOH) 233-236 °C; 1 H NMR (CDCl 3 ) δ 8.01 (dd,J = 8.4,0.6 Hz,1 H,H-5'),7.98 (s,1 H,H-3'),7.94 (dd,J = 8.3,0.6 Hz,1 H,H -8'),7.68 (ddd,J = 8.3,7.0,1.2 Hz,1 H,H-7'),7.44-7.50 (m,2 H,H-4,H-6'),7.27 (br s ,1 H,6-NH),6.92 (s,1 H,H-7),4.87 (pent,J = 8.8 Hz,1 H,1-CH),3.46 (s,3 H,3-CH 3 ),2.65 (s,3 H,2’-CH 3 ),1.95-2.10 (m,4 H,2 × CH 2 ),1.80-1.90 (m,2 H,CH 2 ),1.68-1.75 (m,2 H,CH 2 ); MS m / z 374.2 (MH + ,100%); HRMS calcd for C 22 H 24 N 5 O (MH + ) m / z 374.1975,found 374.1986 (-2.8 ppm). HPLC purity 100.0%.

[0360] Example 62: SN39326 1-Cyclopentyl-3-methyl-6-(quinoxalin-6-ylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (68) [ka] Chloride 6 (121 mg, 0.48 mmol), Quinoxaline-6-amine (83 mg, 0.58 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (344 mg, 1.06 mmol) in dioxane (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 68 (146 mg, 84%) as a yellow powder, eluting with EtOAc. mp (EtOAc / pet. ether) 230-232 °C; 1 H NMR (CDCl 3 ) δ 8.74 (d,J = 1.9 Hz,1 H,H-2'),8.65 (d,J = 1.9 Hz,1 H,H-3'),8.13 (d,J = 2.5 Hz,1 H, H-5'),8.00 (d,J = 9.1 Hz,1 H,H-8'),7.93 (s,1 H,H-4),7.67 (dd,J = 9.1,2.5 Hz,1 H, H-7'),6.99 (br s,1 H,6-NH),6.77 (s,1 H,H-7),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.44 ( s,3H,3-CH 3 ),2.01-2.10 (m,4 H,2 × CH 2 ),1.86-1.96 (m,2 H,CH 2 ),1.66-1.76 (m,2 H,CH 2 ); MS m / z 361.2 (MH + ,100%); HRMS calcd for C 20 H 21 N 6 O (MH + ) m / z 361.1761,found 361.1778 (-1.8 ppm). HPLC purity 100.0%.

[0361] Example 63: SN39402 6-(benzo[d][1,3]dioxol-5-ylamino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2 -on (69) [ka] Chloride 6 (133 mg, 0.53 mmol), benzo[d][1,3]dioxol-5-amine (87 mg, 0.63 mmol), Pd 2 dba 3 (24 mg, 24 μmol), XPhos (51 mg, 106 μmol), and Cs 2 C.O. 3 A degassed mixture of (380 mg, 1.17 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (50-70% EtOAc / petroleum ether) to give imidazopyridinone 69 (130 mg, 70%) as a tan powder. 1 H NMR (CDCl 3 ) δ 7.78 (s,1 H,H-4),6.88 (d,J = 2.1 Hz,1 H,H-4'),6.78 (d,J = 8.2 Hz,1 H,H-7'), 6.69 (dd,J = 8.2,2.2 Hz,1 H,H-6'),6.45 (d,J = 0.4 Hz,1 H,H-7),6.31 (br s,1 H,6-NH), 5.96 (s,2 H,H-2'),4.73 (pent,J = 8.8 Hz,1 H,1-CH),3.38 (s,3 H,3-CH 3 ),1.95-2.04 (m,4 H,2 × CH 2 ),1.80-1.90 (m,2 H,CH 2 ),1.62-1.70 (m,2 H,CH 2 ); MS m / z 353.2 (MH + ,100%). HPLC purity 99.8%.

[0362] Example 64: SN39441 6-(benzo[d]thiazol-6-ylamino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (70) [ka] Chloride 6 (126 mg, 0.50 mmol), benzo[d]thiazol-6-amine (90 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (50-100% EtOAc / petroleum ether) to give imidazopyridinone 70 (12 mg, 7%) as a gum. 1 H NMR (CDCl 3 ) δ 8.84 (s,1 H,H-2'),8.12 (d,J = 2.2 Hz,1 H,H-7'),8.03 (d,J = 8.8 Hz,1 H,H-4') ,7.87 (s,1 H,H-4),7.33 (dd,J = 8.8,2.2 Hz,1 H,H-5'),6.65 (br s,1 H,6-NH),6.61 (s, 1 H,H-7),4.79 (pent,J = 8.7 Hz,1 H,1-CH),3.41 (s,3 H,3-CH 3 ),1.98-2.04 (m,4 H,2 × CH 2 ),1.82-1.90 (m,2 H,CH 2 ),1.65-1.74 (m,2 H,CH 2 ); MS m / z 366.2 (MH + ,100%); HRMS calcd for C 19 H 20 N 5 OS (MH + ) m / z 366.1370,found 366.1374 (-1.2 ppm). HPLC purity 96.3%.

[0363] Example 65: SN39333 1-Cyclopentyl-3-methyl-6-(pyridin-4-ylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (71) [ka] Chloride 6 (124 mg, 0.49 mmol), 4-aminopyridine (56 mg, 0.59 mmol), Pd 2 dba 3 (22 mg, 25 μmol), XPhos (47 mg, 98 μmol), and Cs 2 C.O. 3 A degassed mixture of (351 mg, 1.08 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-20%) of MeOH / EtOAc to give imidazopyridinone 71 (54 mg, 35%) as a white powder. mp (EtOAc) 250-252 °C; 1 H NMR (CDCl 3 ) δ 8.37 (dd,J = 4.9,1.4 Hz,2 H,H-2',H-6'),7.93 (s,1 H,H-4),7.28 (dd,J = 4.9,1.5 Hz, 2 H,H-3',H-5'),7.00 (br s,1 H,6-NH),6.67 (d,J = 0.4 Hz,1 H,H-7),4.81 (pent,J = 8.8Hz,1H,1-CH),3.43(s,3H,3-CH 3 ),1.99-2.09 (m,4 H,2 × CH 2 ),1.87-1.97 (m,2 H,CH 2 ),1.68-1.78 (m,2 H,CH 2 ); MS m / z 310.2 (MH + ,100%); HRMS calcd for C 17 H 20 N 5 O (MH + ) m / z 310.1662,found 310.1668 (-1.8 ppm). HPLC purity 98.0%.

[0364] Example 66: SN39334 1-Cyclopentyl-3-methyl-6-(pyridin-3-ylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (72) [ka] Chloride 6 (117 mg, 0.47 mmol), 3-aminopyridine (53 mg, 0.56 mmol), Pd 2 dba 3 (22 mg, 25 μmol), XPhos (45 mg, 94 μmol), and Cs 2 C.O. 3 A degassed mixture of (337 mg, 1.03 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatographic methods eluting with a gradient (0-10%) of MeOH / EtOAc to give imidazopyridinone 72 (121 mg, 84%) as a white powder. mp (EtOAc) 203-206 °C; 1 H NMR (CDCl 3 ) δ 8.57 (d,J = 2.5 Hz,1 H,H-2'),8.23 (dd,J = 4.7,1.4 Hz,1 H,H-6'),7.88 (ddd,J = 8.3,2.7, 1.4 Hz,1 H,H-5'),7.84 (s,1 H,H-4),7.23 (dd,J = 8.3,4.7 Hz,1 H,H-4'),6.50-6.55 (m, 2 H,6-NH,H-7),4.79 (pent,J = 8.8 Hz,1 H,1-CH),3.40 (s,3 H,3-CH 3 ),1.97-2.07 (m,4 H,2 × CH 2 ),1.83-1.95 (m,2 H,CH 2 ),1.65-1.68 (m,2 H,CH 2 ); MS m / z 310.2 (MH + ,100%); HRMS calcd for C 17 H 20 N 5 O (MH + ) m / z 310.1662,found 310.1668 (-1.9 ppm). HPLC purity 98.5%.

[0365] Example 67: SN39341 1-Cyclopentyl-3-methyl-6-(pyridin-2-ylamino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (73) [ka] Chloride 6 (122 mg, 0.49 mmol), 2-aminopyridine (55 mg, 0.58 mmol), Pd 2 dba 3 (22 mg, 25 μmol), XPhos (47 mg, 98 μmol), and Cs 2 C.O. 3 A degassed mixture of (351 mg, 1.08 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-5%) of MeOH / EtOAc to give imidazopyridinone 73 (112 mg, 75%) as a tan powder. mp (EtOAc) 151-153 °C; 1 H NMR (CDCl 3 ) δ 8.25 (ddd,J = 5.0,1.8,0.7 Hz,1 H,H-6'),7.93 (s,1 H,H-4),7.86 (s,1 H,H-7),7.56 ( ddd,J = 8.4,7.2,1.9 Hz,1 H,H-4'),7.49 (br s,1 H,6-NH),7.10 (d,J = 8.4 Hz,1 H,H-3') ,6.81 (ddd,J = 7.2,5.0,0.8 Hz,1 H,H-5'),4.87 (pent,J = 8.4 Hz,1 H,1-CH),3.41 (s,3 H,3-CH 3 ),1.98-2.13 (m,6 H,3 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ); MS m / z 310.2 (MH + ,100%); HRMS calcd for C 17 H 20 N 5 O (MH + ) m / z 310.1662,found 310.1665 (-0.8 ppm). HPLC purity 99.9%.

[0366] Example 68: SN39344 1-Cyclopentyl-3-methyl-6-((3-methylpyridin-4-yl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 74) [ka] Chloride 6 (137 mg, 0.54 mmol), 3-methylpyridin-4-amine (71 mg, 0.65 mmol), Pd 2 dba 3 (25 mg, 27 μmol), XPhos (51 mg, 108 μmol), and Cs 2 C.O. 3 A degassed mixture of (387 mg, 1.19 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-20%) of MeOH / EtOAc to give imidazopyridinone 74 (150 mg, 85%) as a brown cube. mp (EtOAc) 217-220 °C; 1 H NMR (CDCl 3 ) δ 8.27-8.31 (m,2 H,H-2',H-6'),7.93 (s,1 H,H-4),7.52 (d,J = 5.7 Hz,1 H,H-5' ),6.76 (d,J = 0.4 Hz,1 H,H-7),6.40 (br s,1 H,6-NH),4.81 (pent,J = 8.8 Hz,1 H,1-CH),3.44 (s,3 H,3-CH 3 ),2.74 (s,3 H,3’-CH 3 ),2.00-2.09 (m,4 H,2 × CH 2 ),1.78-1.85 (m,2 H,CH 2 ),1.70-1.78 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%); HRMS calcd for C 18 H 22 N 5 O (MH + ) m / z 324.1819,found 324.1825 (-1.9 ppm). HPLC purity 99.5%.

[0367] Example 69: SN39361 1-Cyclopentyl-3-methyl-6-((2-methylpyridin-4-yl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 75) [ka] Chloride 6 (129 mg, 0.51 mmol), 2-methylpyridin-4-amine (67 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (49 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH / EtOAc to give imidazopyridinone 75 (127 mg, 77%) as a milky white powder. mp (EtOAc) 214-216 °C; 1 H NMR (CDCl 3 ) δ 8.25 (d,J = 5.8 Hz,1 H,H-6'),7.93 (s,1 H,H-4),7.16 (d,J = 2.1 Hz,1 H,H-3'), 7.06 (dd,J = 5.8,2.2 Hz,1 H,H-5'),7.03 (br s,1 H,6-NH),6.70 (s,1 H,H-7),4.83 (pent,J = 8.7 Hz,1 H,1-CH),3.43 (s,3 H,3-CH 3 ),2.49 (s,3 H,2’-CH 3 ),2.00-2.10 (m,4 H,2 × CH 2 ),1.87-1.96 (m,2 H,CH 2 ),1.70-1.78 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%); HRMS calcd for C 18 H 22 N 5 O (MH + ) m / z 324.1819,found 324.1820 (-0.2 ppm). HPLC purity 99.0%.

[0368] Example 70: SN39346 1-Cyclopentyl-3-methyl-6-((2-methylpyridin-3-yl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 76) [ka] Chloride 6 (125 mg, 0.50 mmol), 2-methylpyridin-3-amine (64 mg, 0.60 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (48 mg, 100 μmol), and Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 76 (103 mg, 64%) as tan crystals, eluting with EtOAc. mp (EtOAc) 144-146 °C; 1 H NMR (CDCl 3 ) δ 8.22 (dd,J = 4.8,1.4 Hz,1 H,H-6'),7.82-7.86 (m,2 H,H-4,H-4'),7.14 (dd,J = 8.1,4.8 Hz,1 H,H-5'),6.41 (d,J = 0.6 Hz,1 H,H-7),6.14 (br s,1 H,6-NH),4.75 (pent,J = 8.8 Hz, 1 H,1-CH),3.41 (s,3 H,3-CH 3 ),2.55 (s,3 H,2’-CH 3 ),1.95-2.05 (m,4 H,2 × CH 2 ),1.80-1.88 (m,2 H,CH 2 ),1.64-1.72 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%); HRMS calcd for C 18 H 22 N 5 O (MH + ) m / z 324.1819,found 324.1819 (-0.1 ppm). HPLC purity 99.7%.

[0369] Example 71: SN39362 1-Cyclopentyl-3-methyl-6-((5-methylpyridin-3-yl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 77) [ka] Chloride 6 (118 mg, 0.47 mmol), 5-methylpyridin-3-amine (61 mg, 0.56 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (45 mg, 94 μmol), and Cs 2 C.O. 3 A degassed mixture of (337 mg, 1.03 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH / EtOAc to give imidazopyridinone 77 (129 mg, 78%) as a milky white powder. mp (EtOAc) 182-185 °C; 1 H NMR (CDCl 3 ) δ 8.37 (d,J = 2.5 Hz,1 H,H-6'),8.07 (d,J = 1.2 Hz,1 H,H-2'),7.85 (s,1 H,H-4), 7.69 (br s,1 H,H-4'),6.62 (br s,1 H,6-NH),6.55 (d,J = 0.5 Hz,1 H,H-7),4.79 (pent,J = 8.8Hz,1H,1-CH),3.40(s,3H,3-CH 3 ),2.33 (s,3 H,5’-CH 3 ),1.96-2.07 (m,4 H,2 × CH 2 ),1.84-1.92 (m,2 H,CH 2 ),1.68-1.75 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%); HRMS calcd for C 18 H 22 N 5 O (MH +) m / z 324.1819,found 324.1821 (-0.6 ppm). HPLC purity 94.3%.

[0370] Example 72: SN39342 1-Cyclopentyl-3-methyl-6-((4-methylpyridin-3-yl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 78) [ka] Chloride 6 (127 mg, 0.51 mmol), 4-methylpyridin-3-amine (66 mg, 0.61 mmol) Pd 2 dba 3 (23mg, 26μmol), XPhos (49mg, 102μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH / EtOAc to give imidazopyridinone 78 (99 mg, 61%) as a brown foam. 1 H NMR (CDCl 3 ) δ 8.69 (s,1 H,H-2'),8.25 (d,J = 4.8 Hz,1 H,H-6'),7.81 (s,1 H,H-4),7.17 (d,J = 4.8 Hz,1 H,H-5'),6.39 (d,J = 0.5 Hz,1 H,H-7),6.14 (br s,1 H,6-NH),4.70 (pent,J = 8.8 Hz,1 H,1-CH),3.40 (s,3 H,3-CH 3 ),2.30 (s,3 H,4’-CH 3 ),1.95-2.02 (m,4 H,2 × CH 2 ),1.80-1.90 (m,2 H,CH 2 ),1.63-1.72 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%); HRMS calcd for C 18 H 22 N 5 O (MH + ) m / z 324.1819,found 324.1816 (1.0 ppm). HPLC purity 98.6%.

[0371] Example 73: SN39360 1-cyclopentyl-3-methyl-6-((3-methylpyridin-2-yl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 79) [ka] Chloride 6 (125 mg, 0.50 mmol), 3-methylpyridin-2-amine (64 mg, 0.60 mmol), Pd 2 dba 3 (23mg, 25μmol), XPhos(48mg, 100μmol)Cs 2 C.O. 3 A degassed mixture of (358 mg, 1.10 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (70-100% EA / petroleum ether) to yield imidazopyridinone 79 (149 mg, 93%) as a tan powder. mp (EtOAc / pet ether) 169-172 °C; 1 H NMR (CDCl 3 ) δ 8.04 (d,J = 0.5 Hz,1 H,H-4),7.85 (s,1 H,H-7),7.45 (dd,J = 8.2,7.4 Hz,1 H,H-5') ,7.28 (s,1 H,6-NH),6.79 (d,J = 8.2 Hz,1 H,H-6'),6.67 (d,J = 7.4 Hz,1 H,H-4'),4.92 (pent,J = 8.7 Hz,1 H,1-CH),3.41 (s,3 H,3-CH 3 ),2.48 (s,3 H,3’-CH 3 ),1.98-2.16 (m,6 H,3 × CH 2 ),1.72-1.80 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%); HRMS calcd for C 18 H 22 N 5 O (MH + ) m / z 324.1819,found 324.1818 (0.4 ppm). HPLC purity 99.6%.

[0372] Example 74: SN39405 1-cyclopentyl-6-((6-methoxy-4-methylpyridin-3-yl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine- 2-on(80) [ka] Chloride 6 (129 mg, 0.51 mmol), 5-methoxy-3-methylpyridin-2-amine (85 mg, 0.61 mmol), Pd 2 dba 3 (23mg, 26μmol), XPhos (49mg, 102μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (70-100% EtOAc / petroleum ether) to yield imidazopyridinone 80 (4 mg, 2%) as a clear oil. 1 H NMR (CDCl 3 ) δ 8.11 (s,1 H,H-2'),7.45 (s,1 H,H-4),6.69 (s,1 H,H-5'),6.03 (s,1 H,H-7 ),5.97 (br s,1 H,6-NH),4.64 (pent,J = 8.7 Hz,1 H,1-CH),3.93 (s,3 H,6'-OCH 3 ),3.37 (s,3 H,3-CH 3 ),2.16 (s,3 H,4’-CH 3 ),1.74-1.82 (m,4 H,2 × CH 2 ),1.57-1.67 (m,2 H,CH 2 ),1.58-1.67 (m,2 H,CH 2 ); MS m / z 354.2 (MH + ,100%); HRMS calcd for C 19 H 24 N 5 O 2 (MH + ) m / z 354.1925,found 354.1922 (0.6 ppm).

[0373] Example 75: SN39395 1-Cyclopentyl-6-((6-methoxypyrimidin-4-yl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 81) [ka] Chloride 6 (128 mg, 0.51 mmol), 6-methoxypyrimidin-4-amine (76 mg, 0.61 mmol), Pd 2 dba 3 (23 mg, 25 μmol), XPhos (49 mg, 102 μmol), and Cs 2 C.O. 3 A degassed mixture of (366 mg, 1.12 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 81 (88 mg, 51%) as white crystals. mp (EtOAc / pet ether) 180-182 °C; 1 H NMR (CDCl 3 ) δ 8.44 (d,J = 0.8 Hz,1 H,H-2'),7.90 (d,J = 0.4 Hz,1 H,H-4),7.82 (br s,1 H,6-NH), 7.43 (s,1 H,H-5'),6.76 (d,J = 0.7 Hz,1 H,H-7),4.85 (pent,J = 8.8 Hz,1 H,1-CH),3.96 (s ,3H,6'-OCH 3 ),3.43 (s,3 H,3-CH 3 ),1.94-2.10 (m,6 H,3 × CH 2),1.72-1.80 (m,2 H,CH 2 ); HRMS calcd for C 17 H 21 N 6 O 2 (MH + ) m / z 341.1721,found 371.1711 (2.7 ppm). HPLC purity 99.8%.

[0374] Example 76: SN39258 6-((4-aminophenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (82) [ka] A mixture of Pd / C (10 mg) with nitroaniline 17 (66 mg, 0.19 mol) in EtOH / EtOAc (1:1, 30 mL) was purified with H 2 (50psi) for 3 hours. The mixture was filtered through diatomaceous earth, the matte was washed with EtOH (20 mL) and the combined filtrates were evaporated. The residue was crystallized to give imidazopyridinone 82 (40 mg, 66%) as a brown powder. mp (EtOAc / pet ether) 171-173 °C; 1 H NMR (CDCl 3 ) δ 7.74 (d,J = 0.4 Hz,1 H,H-4),7.08 (ddd,J = 8.6,3.1,2.1 Hz,2 H,H-2',H-6'),6.71 (ddd, J = 8.6,3.1,2.1 Hz,2 H,H-3',H-5'),6.37 (d,J = 0.6 Hz,1 H,H-7),6.21 (s,1 H,6-NH ),4.70 (pent,J = 8.7 Hz,1 H,1-CH),3.62 (br s,2 H,4'-NH 2 ),3.37 (s,3 H,3-CH 3 ),1.92-1.98 (m,4 H,2 × CH 2 ),1.76-1.86 (m,2 H,CH 2 ),1.59-1.60 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%).Anal calcd for C 18 H 21 N 5 O·1 / 4H 2 O: C,65.93; H,6.61; N,21.36. Found: C,65.90; H,6.37; N,21.47%. HPLC purity 99.3%.

[0375] Example 77: SN39259 6-((3-aminophenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (83) [ka] A mixture of nitroaniline 18 (80 mg, 0.23 mmol) and Pd / C (10 mg) in EtOH / EtOAc (1:1, 30 mL) was purified with H 2 (50psi) for 3 hours. The mixture was filtered through diatomaceous earth, the matte was washed with EtOH (20 mL) and the combined filtrates were evaporated. The residue was crystallized to give imidazopyridinone 83 (40 mg, 54%) as a tan powder. mp (EtOAc / pet ether) 151-153 °C; 1 H NMR (CDCl 3 ) δ 7.81 (s,1 H,H-4),7.10 (d,J = 7.9 Hz,1 H,H-5'),6.67 (d,J = 0.6 Hz,1 H,H-7),6.61 -6.65 (m,2 H,H-2',H-6'),6.39 (br s,1 H,6-NH),7.35 (ddd,J = 7.9,2.1,0.9 Hz,1 H,H- 4'),4.77 (pent,J = 8.7 Hz,1 H,1-CH),3.68 (br s,2 H,3'-NH 2 ),3.39 (s,3 H,3-CH 3 ),1.97-2.05 (m,4 H,2 × CH 2 ),1.83-1.93 (m,2 H,CH 2 ),1.64-1.74 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%).Anal calcd for C 18 H 21 N 5 O: C,66.85; H,6.55; N,21.66. Found: C,66.93; H,6.56; N,21.57%. HPLC purity 97.9%.

[0376] Example 78: SN39272 6-((2-aminophenyl)amino)-1-cyclopentyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (84) [ka] A mixture of nitroaniline 19 (100 mg, 0.28 mmol) and Pd / C (10 mg) in EtOH / EtOAc (1:1, 30 mL) was purified with H 2 (50psi) for 3 hours. The mixture was filtered through diatomaceous earth, the matte was washed with EtOH (20 mL) and the combined filtrates were evaporated. The residue was crystallized to give imidazopyridinone 84 (56 mg, 62%) as pink needles. mp (EtOAc / pet ether) 150-151 °C; 1 H NMR (CDCl 3 ) δ 7.77 (s,1 H,H-4),7.18 (dd,J = 7.8,1.3 Hz,1 H,H-6'),7.07 (ddd,J = 7.7,7.6,1.4 Hz,1 H, H-4'),6.83 (dd,J = 7.9,1.4 Hz,1 H,H-3'),6.78 (dt,J = 7.6,1.4 Hz,1 H,H-5'),6.14 (d, J = 0.6 Hz,1 H,H-7),6.03 (br s,1 H,6-NH),4.68 (pent,J = 8.7 Hz,1 H,1-CH),3.86 (br s,2 H ,2'-NH 2 ),3.39 (s,3 H,3-CH 3 ),1.89-1.97 (m,4 H,2 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ),1.56-1.66 (m,2 H,CH 2 ); MS m / z 324.2 (MH + ,100%).Anal calcd for C 18 H 21 N 5 O: C,66.85; H,6.55; N,21.66. Found: C,66.97; H,6.57; N,21.44%. HPLC purity 99.6%.

[0377] Example 79: SN39305 1-cyclopentyl-6-((4-hydroxyphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (85) [ka] A mixture of benzyl ether 34 (130 mg, 0.31 mmol) and Pd / C (25 mg) in EtOAc (25 ml) and EtOH (25 ml) was heated with H 2 (50 psi) at 20° C. for 16 hours. The mixture was filtered through diatomaceous earth and the filtrate was evaporated. The residue was purified by chromatography eluting with a gradient (80-100%) of EtOAc / petroleum ether to give imidazopyridinone 85 (73 mg, 72%) as opalescent crystals. mp (EtOAc / pet ether) 257-260 °C; 1 H NMR [(CD 3 ) 2 SO] δ 8.84 (s,1 H,4'-OH),8.34 (s,1 H,6-NH),7.83 (s,1 H,H-4),7.36 (ddd,J = 8.9,3.4, 2.1 Hz,2 H,H-2',H-6'),6.65 (ddd,J = 8.9,3.4,2.1 Hz,2 H,H-3',H-5'),6.50 (s,1 H ,H-7),4.70 (pent,J = 8.4 Hz,1 H,1-CH),3.27 (s,3 H,3-CH 3 ),1.85-1.96 (m,6 H,3 × CH 2 ),1.63-1.70 (m,2 H,CH 2 ); MS m / z 325.2 (MH + ,100%). Anal. calcd for C 18 H 20 N 4 O 2 ·0.2EtOAc: C,66.02; H,6.38; N,16.38. Found: C,66.10; H,6.61; N,16.73%. HPLC purity 99.9%.

[0378] Example 80: SN39306 1-cyclopentyl-6-((3-hydroxyphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (86) [ka] A mixture of benzyl ether 35 (198 mg, 0.31 mol) and Pd / C (25 mg) in EtOAc (25 ml) and EtOH (25 ml) was heated with H 2(50 psi) at 20° C. for 16 hours. The mixture was filtered through diatomaceous earth and the filtrate was evaporated. The residue was purified by chromatography eluting with a gradient (80-100%) of EtOAc / petroleum ether to give imidazopyridinone 86 (97 mg, 63%) as white crystals. mp (EtOAc / pet ether) 216-218 °C; 1 H NMR [(CD 3 ) 2 SO] δ 9.11 (s,1 H,4'-OH),8.64 (s,1 H,6-NH),7.92 (s,1 H,H-4),7.20 (d,J = 2.0 Hz,1 H,H-2'),7.93-7.01 (m,2 H,H-5',H-6'),6.64 (s,1 H,H-7),6.24 (dt,J = 6.9,2.2 Hz ,1 H,H-4'),4.72 (pent,J = 8.8 Hz,1 H,1-CH),3.30 (s,3 H,3-CH 3 ),1.87-1.97 (m,6 H,3 × CH 2 ),1.65-1.72 (m,2 H,CH 2 ); MS m / z 325.2 (MH + ,100%). Anal. calcd for C 18 H 20 N 4 O 2 ·0.2EtOAc: C,66.02; H,6.37; N,16.38. Found: C,65.91; H,6.50; N,16.38%. HPLC purity 99.2%.

[0379] Example 81: SN39329 1-cyclopentyl-6-((2-hydroxyphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (87) [ka] A mixture of benzyl ether 36 (108 mg, 0.26 mmol) and Pd / C (20 mg) in a mixture of EtOAc (25 mL) and EtOH (25 mL) was stirred with H2 (50 psi) at 20 C for 16 h. The mixture was filtered through diatomaceous earth and the filtrate was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 87 (46 mg, 55%) as a white powder. mp (EtOAc / pet. ether) 160-163 °C; 1 H NMR [(CD 3 ) 2 SO] δ 10.53 (s,1 H,OH),8.14 (br s,1 H,6-NH),7.88 (s,1 H,H-4),7.78 (dd,J = 7.7,1.8 Hz,1 H,H-6'),6.88 (s,1 H,H-7),6.82 (dd,J = 7.7,1.8 Hz,1 H,H-3'),6.77 (ddd,J = 7.7,7.2, 1.8 Hz,1 H,H-4'),6.72 (ddd,J = 7.7,7.2,1.8 Hz,1 H,H-5'),4.70 (pent,J = 8.6 Hz,1 H,1-CH) ,3.29 (s,3H,3-CH 3 ),1.89-1.99 (m,6 H,3 × CH 2 ),1.60-1.70 (m,2 H,CH 2 ); MS m / z 325.2 (MH + ,100%); HRMS calcd for C 18 H 21 N 4 O 2 (MH + ) m / z 325.1659,found 325.1666 (-2.2 ppm). HPLC purity 99.0%.

[0380] Example 82: SN39375 1-Cyclopentyl-6-((4-hydroxy-2-methylphenyl)amino)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 88) [ka] A mixture of benzyl ether 51 (172 mg, 0.40 mol) and Pd / C (20 mg) in EtOAc (25 ml) and EtOH (25 ml) was diluted with hH 2 (50 psi) at 20° C. for 16 hours. The mixture was filtered through diatomaceous earth and the filtrate was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give imidazopyridinone 88 (44 mg, 32%) as a pink powder. mp (EtOAc / pet. ether) 244-246 °C; 1 H NMR [(CD 3 ) 2 SO] δ 9.03 (s,1 H,4'-OH),7.76 (br s,1 H,6-NH),7.57 (s,1 H,H-4),7.14 (d,J = 8.5 Hz, 1 H,H-6'),6.54 (dd,J = 8.5,2.8 Hz,1 H,H-5'),6.62 (d,J = 2.7 Hz,1 H,H-3'),6.25 (s ,1 H,H-7),4.64 (pent,J = 8.7 Hz,1 H,1-CH),3.25 (s,3 H,3-CH 3 ),2.09 (s,3 H,2’-CH 3 ),1.82-1.89 (m,4 H,2 × CH 2 ),1.72-1.82 (m,2 H,CH 2 ),1.58-1.68 (m,2 H,CH 2 ); MS m / z 339.2 (MH + ,100%); HRMS calcd for C 19 H 23 N 4 O 2 (MH + ) m / z 339.1816,found 339.1811 (1.3 ppm). HPLC purity 99.2%.

[0381] Example 83: SN39777 3-Benzyl-1-cyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 94) [ka] 3-Benzyl-6-chloro-1-cyclopentyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (89): imidazopyridinone 5 (321 mg, 1.35 mol) and benzyl bromine (0.24 mL, 2.03 mol) in dry DMF (5 mL) at 5 °C was added NaH (60% dispersion, 65 mg, 1.62 mol). The mixture was stirred at 20°C for 16 hours, then quenched with ice / water (5ml) and partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (10-20%) of EtOAc / petroleum ether to give chloride 89 (352 mg, 80%) as a tan oil. 1 H NMR (CDCl 3 ) δ 7.83 (d,J = 0.5 Hz,1 H,H-4),7.27-7.38 (m,5 H,aryl-H),6.98 (d,J = 0.5 Hz,1 H,H-7), 5.05 (s,2H,3-CH 2 ),4.82 (pent,J = 8.7 Hz,1 H,1-CH),1.93-2.10 (m,6 H,3 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ); MS m / z 328.2 (MH + ,100%),330.2 (MH + ,35%).HRMS calcd for C 18 H 19 35 ClN 3 O (MH + ) m / z 328.1211,found 328.1223 (-3.7 ppm). 3-Benzyl-1-cyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (94): Chloride Product 89 (170 mg, 0.52 mmol), 4-methoxy-2-methylaniline (85 mg, 0.62 mmol), Pd 2 dba 3 (24 mg, 26 μmol), XPhos (50 mg, 104 μmol), and Cs 2 C.O. 3 A degassed mixture of (373 mg, 1.14 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-50%) of EtOAc / petroleum ether to give imidazopyridinone 94 (70 mg, 31%) as a tan foam. 1 H NMR (CDCl 3) δ 7.62 (d,J = 0.4 Hz,1 H,H-4),7.27-7.34 (m,5 H,aryl-H),7.20 (d,J = 8.6 Hz,1 H,H-6') ,6.82 (d,J = 2.9 Hz,1 H,H-3'),6.75 (dd,J = 8.6,2.9 Hz,1 H,H-5'),6.10 (d,J = 0.5 Hz,1 H ,H-7),5.94 (br s,1 H,6-NH),4.98 (s,2 H,3-CH 2 ),4.70 (pent,J = 8.7 Hz,1 H,1-CH),3.81 (s,3 H,4’-OCH 3 ),2.23 (s,3 H,2’-CH 3 ),1.92-1.98 (m,4 H,2 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ),1.56-1.66 (m,2 H,CH 2 ); MS m / z 429.2 (MH + ,100%). HRMS calcd for C 26 H 29 N 4 O 2 (MH + ) m / z 429.2285,found 429.2298 (-3.0 ppm). HPLC purity 98.7%.

[0382] Example 84: SN39778 1,3-dicyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (95 ) [ka] 6-chloro-1,3-dicyclopentyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (90): pyridinone 5 (300 mg, 1.26 mmol) and iodocyclopentane (0.22 mL, 1.89 mmol) in dry DMF (5 mL) was added NaH (60% dispersion, 61 mg, 1.51 mmol) at 5°C. The mixture was stirred at 20°C for 16 hours, then quenched with ice / water (5ml) and partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (10-20%) of EtOAc / petroleum ether to give chloride 90 (215 mg, 56%) as a tan oil. 1 H NMR (CDCl 3 ) δ 8.04 (d,J = 0.4 Hz,1 H,H-4),6.98 (d,J = 0.4 Hz,1 H,H-7),4.75-4.87 (m,2 H,1-CH,3 -CH),1.91-2.08 (m,12 H,6 × CH 2 ),1.70-1.78 (m,4 H,2 × CH 2 ); MS m / z 306.2 (MH + ,100%),308.2 (MH + ,35%).HRMS calcd for C 16 H 21 35 ClN 3 O (MH + ) m / z 306.1368,found 306.1374 (-2.2 ppm). 1,3-Dicyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (95): Chloride 90 (190 mg, 0.62 mmol), 4-methoxy-2-methylaniline (103 mg, 0.75 mmol), Pd 2 dba 3 (28 mg, 31 μmol), XPhos (59 mg, 124 μmol), and Cs 2 C.O. 3 A degassed mixture of (444 mg, 1.36 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (25-30%) of EtOAc / petroleum ether to give imidazopyridinone 95 (51 mg, 20%) as a tan powder. mp 163-165 °C; 1 H NMR (CDCl 3 ) δ 7.84 (d,J = 0.5 Hz,1 H,H-4),7.23 (d,J = 8.6 Hz,1 H,H-6'),6.84 (d,J = 2.9 Hz,1 H,H -3'),6.77 (dd,J = 8.6,2.9 Hz,1 H,H-5'),6.12 (d,J = 0.5 Hz,1 H,H-7),5.96 (br s,1 H, 6-NH),4.81 (pent,J = 8.8 Hz,1 H,3-CH),4.68 (pent,J = 8.8 Hz,1 H,1-CH),3.82 (s,3 H,4'-OCH 3 ),2.25 (s,3 H,2’-CH 3 ),2.00-2.07 (m,4 H,2 × CH 2 ),1.88-1.97 (m,6 H,3 × CH 2 ),1.69-1.78 (m,4 H,2 × CH 2 ),1.57-1.67 (m,2 H,CH 2 ); MS m / z 407.2 (MH + ,100%). HRMS calcd for C 24 H 31 N 4 O 2 (MH + ) m / z 407.2441,found 407.2437 (-1.2 ppm). HPLC purity 99.4%.

[0383] Example 85: SN39790 1-cyclopentyl-3-isopropyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one( 96) [ka] 6-chloro-1-cyclopentyl-3-isopropyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (91): pyridinone 5 (0.30 g, 1.3 mmol) and isopropyl bromide ( To a stirred solution of 0.18 mL, 1.9 mmol) in dry DMF (5 mL) was added NaH (60% dispersion, 61 mg, 1.5 mmol) at 5°C. The mixture was stirred at 20°C for 16 hours, then quenched with ice / water (5ml) and partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 mL), brine (50 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give chloride 91 (235 mg, 67%) as a white solid, eluting with 20% EtOAc / petroleum ether. mp 129-131 °C; 1 H NMR (CDCl 3 ) δ 8.12 (d,J = 0.4 Hz,1 H,H-4),6.98 (d,J = 0.4 Hz,1 H,H-7),4.78 (pent,J = 8.7 Hz,1 H,1- CH),4.72 (sept,J = 7.0 Hz,1 H,3-CH),1.93-2.07 (m,6 H,3 × CH 2 ),1.72-1.78 (m,2 H,CH 2 ),1.52 (d,J = 7.0 Hz,6 H,2 × CH 3 ); MS m / z 280.2 (MH + ,100%),282.2 (MH + ,35%).HRMS calcd for C 14 H 19 35 ClN 3 O (MH + ) m / z 280.1211,found 280.1217 (-2.1 ppm). 1-Cyclopentyl-3-isopropyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (96): Chloride Product 91 (123 mg, 0.44 mmol), 4-methoxy-2-methylaniline (72 mg, 0.53 mmol), Pd 2 dba 3 (20 mg, 22 μmol), XPhos (42 mg, 88 μmol), and Cs 2 C.O. 3 A degassed mixture of (315 mg, 0.97 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 96 (46 mg, 12%) as a red solid, eluting with 50% EtOAc / petroleum ether. mp 140-142 °C; 1 H NMR (CDCl 3) δ 7.93 (d,J = 0.5 Hz,1 H,H-4),7.22 (d,J = 8.6 Hz,1 H,H-6'),6.84 (d,J = 2.9 Hz,1 H,H -3'),6.77 (dd,J = 8.6,2.9 Hz,1 H,H-5'),6.11 (d,J = 0.5 Hz,1 H,H-7),5.98 (br s,1 H, 6-NH),4.63-4.70 (m,2 H,1-CH,3-CH),3.82 (s,3 H,4'-OCH 3 ),2.26 (s,3 H,2’-CH 3 ),1.88-1.96 (m,4 H,2 × CH 2 ),1.70-1.78 (m,2 H,CH 2 ),1.57-1.66 (m,2 H,CH 2 ),1.51 (d,J = 7.0 Hz,6 H,2 × CH 3 ); MS m / z 381.2 (MH + ,100%). HRMS calcd for C 22 H 28 N 4 O 2 (MH + ) m / z 381.2285,found 381.2295 (-2.7 ppm). HPLC purity 97.7%.

[0384] Example 86: SN39789 1-Cyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-3-(2-methoxyethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridine -2-one(97) [ka] 6-chloro-1-cyclopentyl-3-(2-methoxyethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (92):pyridinone 5 (0.32g, 1.4mmol ) and 1-bromo-2-methoxyethane (0.19 mL, 2.0 mmol) in dry DMF (5 mL) was added NaH (60% dispersion, 65 mg, 1.6 mmol) at 5 °C. The mixture was stirred at 20°C for 16 hours, then quenched with ice / water (5ml) and partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-50%) of EtOAc / petroleum ether to give chloride 92 (301 mg, 75%) as a white solid. mp 80-83 °C; 1 H NMR (CDCl 3 ) δ 8.14 (s,1 H,H-4),6.97 (d,J = 0.4 Hz,1 H,H-7),4.80 (pent,J = 8.7 Hz,1 H,1-CH),4.05 ( dd,J = 5.3,5.0 Hz,2 H,CH 2 O),3.66 (dd,J = 5.3,5.0 Hz,2 H,3-CH 2 ),3.33 (s,3 H,OCH 3 ),1.91-2.09 (m,6 H,3 × CH 2 ),1.69-1.79 (m,2 H,CH 2 ); MS m / z 296.2 (MH + ,100%),298.2 (MH + ,35%).HRMS calcd for C 14 H 19 35 ClN 3 O 2 (MH + ) m / z 296.1160, found 296.1166 (-1.9 ppm). 1-Cyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-3-(2-methoxyethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (97): Chloride 92 (217 mg, 0.73 mmol), 4-methoxy-2-methylaniline (120 mg, 0.88 mmol), Pd 2 dba 3 (33mg, 37μmol), XPhos (70mg, 146μmol), and Cs 2 C.O. 3 A degassed mixture of (523 mg, 1.61 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (60-100%) of EtOAc / petroleum ether to give imidazopyridinone 97 (122 mg, 42%) as a red foam. 1 H NMR (CDCl 3 ) δ 7.90 (d,J = 0.5 Hz,1 H,H-4),7.22 (d,J = 8.6 Hz,1 H,H-6'),6.83 (d,J = 2.9 Hz,1 H,H -3'),6.76 (dd,J = 8.6,3.0 Hz,1 H,H-5'),6.10 (d,J = 0.5 Hz,1 H,H-7),5.98 (br s,1 H, 6-NH),4.67 (pent,J = 8.7 Hz,1 H,1-CH),3.99 (dd,J = 5.4,5.3 Hz,2 H,CH 2 O),3.82 (s,3 H,4’-OCH 3 ),3.66 (dd,J = 5.4,5.3 Hz,2 H,3-CH 2 ),3.34 (s,3 H,OCH 3 ),2.25 (s,3 H,2’-CH 3 ),1.89-1.97 (m,4 H,2 × CH 2 ),1.70-1.79 (m,2 H,CH 2 ),1.57-1.67 (m,2 H,CH 2 ); MS m / z 397.2 (MH + ,100%); HRMS calcd for C 22 H 29 N 4 O 3 (MH + ) m / z 397.2234,found 397.2244 (-2.5 ppm). HPLC purity 96.8%.

[0385] Example 87: SN39793 3-(2-(benzyloxy)ethyl)-1-cyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5- c]pyridin-2-one(98) [ka] 3-(2-(benzyloxy)ethyl)-6-chloro-1-cyclopentyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (93): Pyridinone 5 (0.45g , 1.9 mmol) and benzyl 2-bromodiethyl ether (0.45 mL, 2.8 mmol) in dry DMF (5 ml) was added NaH (60% dispersion, 90 mg, 2.3 mmol) at 5°C. The mixture was stirred at 20°C for 16 hours, then quenched with ice / water (5ml) and partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 mL), brine (50 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (20-50%) of EtOAc / petroleum ether to give chloride 93 (656 mg, 94%) as white crystals. mp 133-135 °C; 1 H NMR (CDCl 3 ) δ 8.14 (d,J = 0.5 Hz,1 H,H-4),7.24-7.31 (m,3 H,aryl-H),7.17-7.20 (m,2 H,aryl-H),6.97 (d ,J = 0.5 Hz,1 H,H-7),4.78 (pent,J = 8.7 Hz,1 H,1-CH),4.49 (s,3 H,CH 2 O),4.07 (dd,J = 5.3,5.0 Hz,2 H,CH 2 O),3.75 (dd,J = 5.3,5.0 Hz,2 H,3-CH 2 ),1.92-2.07 (m,6 H,3 × CH 2 ),1.70-1.78 (m,2 H,CH 2 ); MS m / z 372.2 (MH + ,100%),374.2 (MH + ,35%).HRMS calcd for C 20 H 23 35 ClN 3 O 2 (MH + ) m / z 372.1473,found 372.1477 (-1.0 ppm). 3-(2-(benzyloxy)ethyl)-1-cyclopentyl-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridine- 2-one (98): chloride 93 (614 mg, 1.65 mmol), 4-methoxy-2-methylaniline (272 mg, 1.98 mmol), Pd 2 dba 3 (75 mg, 82 μmol), XPhos (157 mg, 330 μmol), and Cs 2 C.O. 3A degassed mixture of (1.18 g, 3.63 mmol) in MeCN (12 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (50 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-60%) of EtOAc / petroleum ether to give imidazopyridinone 98 (308 mg, 39%) as a tan powder. mp (EtOAc / pet ether) 126-127 °C; 1 H NMR (CDCl 3 ) δ 7.90 (d,J = 0.5 Hz,1 H,H-4),7.21-7.35 (m,6 H,H-6',5 × Aryl-H),6.84 (d,J = 2.9 Hz,1 H,H-3'),6.77 (dd,J = 8.6,3.0 Hz,1 H,H-5'),6.10 (d,J = 0.6 Hz,1 H,H-7),5.98 (br s, 1 H,6-NH),4.67 (pent,J = 8.7 Hz,1 H,1-CH),4.52 (s,2 H,CH 2 O),4.02 (t,J = 5.5 Hz,2 H,CH 2 O),3.81 (s,3 H,4’-OCH 3 ),3.74 (t,J = 5.5 Hz,2 H,3-CH 2 ),2.26 (s,3 H,2’-CH 3 ),1.89-1.97 (m,4 H,2 × CH 2 ),1.70-1.80 (m,2 H,CH 2 ),1.57-1.66 (m,2 H,CH 2 ); MS m / z 473.2 (MH + ,100%). HRMS calcd for C 28 H 33 N 4 O 3 (MH + ) m / z 473.2547,found 473.2557 (-2.0 ppm). HPLC purity 99.7%.

[0386] Example 88: SN39794 1-Cyclopentyl-3-(2-hydroxyethyl)-6-((4-methoxy-2-methylphenyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]pyridine -2-one(99) [ka] A mixture of benzyl ether 98 (255 mg, 0.54 mmol) and Pd / C (30 mg) in HOAc (50 ml) was heated with H 2 Stir vigorously at (60 psi) for 24 hours. The mixture was filtered through diatomaceous earth and washed with EtOAc (20 mL). The solvent was evaporated and the residue was dissolved in EtOAc (80ml) and NaHCONaHCO 3 (50 ml), water (50 ml), and brine (30 ml). Dry the organic fraction (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography to give alcohol 99 (179 mg, 87%) as a white powder, eluting with EtOAc. mp 159-161 °C 1 H NMR (CDCl 3 ) δ 7.85 (d,J = 0.5 Hz,1 H,H-4),7.12 (d,J = 8.6 Hz,1 H,H-6'),6.84 (d,J = 2.9 Hz,1 H,H -3'),6.77 (d,J = 8.6,2.9 Hz,1 H,H-5'),6.09 (d,J = 0.6 Hz,1 H,H-7),6.04 (br s,1 H, 6-NH),4.67 (pent,J = 8.7 Hz,1 H,1-CH),3.95-4.00 (m,4 H,3-CH 2 ,CH 2 O),3.82 (s,3 H,4’-OCH 3 ),2.24 (s,3 H,2’-CH 3 ),1.88-1.98 (m,4 H,2 × CH 2 ),1.70-1.78 (m,2 H,CH 2 ),1.58-1.68 (m,2 H,CH 2 ),OH not observed; MS m / z 383.2 (MH + ,100%). HRMS calcd for C 21 H 27 N 4 O 3 (MH + ) m / z 383.2078,found 383.2082 (-1.7 ppm). HPLC purity 99.4%.

[0387] Example 89: SN39478 6-((4-methoxy-2-methylphenyl)amino)-1-(2-methoxyethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine -2-on(104) [ka] 2-Chloro-N-(2-methoxyethyl)-5-nitropyridin-4-amine (100): Nitropyridine 2 (1.04 g, 5.39 mmol) and iPr 2 To a stirred solution of NEt (1.00 mL, 5.93 mmol) in dry DCM (5 mL) was added dropwise a solution of 2-methoxyethylamine (0.49 mL, 5.66 mmol) in dry DCM (5 mL) at 5°C. The mixture was stirred at 20 °C for 16 h, then diluted with DCM (100 ml), washed with water (3 x 50 ml) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (10-20%) of EtOAc / petroleum ether to give chloride 100 (1.19 g, 95%) as a yellow needle. mp 84-86 °C; 1 H NMR (CDCl 3 ) δ 9.02 (s, 1 H, H-6), 8.36 (br s, 1 H, 4-NH), 6.77 (s, 1 H, H-3), 3.67 (dd, J = 5.4, 5.0 Hz, 2 H, H-2'), 3.49 (dt, J = 5.3, 5.1 Hz, 2 H, H-1'), 3.44 (s, 3 H, 2'-OCH 3 ); MS m / z 232.2 (MH + , 100%), 234.2 (MH + , 35%). Analysis calcd for C 8 H 10 ClN 3 O 3 : C, 41.48; H, 4.35; N, 18.18. Found: C, 41.65; H, 4.24; N, 18.18%. 6-chloro-N 4 -(2-Methoxyethyl)pyridine-3,4-diamine (101): A solution of nitropyridine 100 (1.14 g, 4.95 mmol) in EtOAc (50 mL) was 2 ·2H 2 It was added dropwise to a stirred suspension of O (4.47 g, 19.8 mmol) in EtOAc (100 mL) at a temperature below 60 °C. The mixture was stirred at 60°C for 2 hours, then cooled to 5°C and concentrated (solution). N.H. 3 The solution was added until the solution was basic (pH 9). The resulting precipitate was filtered and washed with EtOAc (100 mL). The combined organic fractions were dried (MgSO 4 ), filtered and evaporated the solvent to obtain diamine 101 as a white powder. mp 130-131 °C; 1 H NMR (CDCl 3 ) δ 7.65 (s,1 H,H-2),6.45 (s,1 H,H-5),4.60 (br s,1 H,4-NH),3.64 (dd,J = 5.3,5.0 Hz, 2 H,H-2'),3.40 (s,3 H,2'-OCH 3 ),3.31 (dt,J = 5.3,5.1 Hz,2 H,H-1’),3.06 (br s,2 H,3-NH 2 ); MS m / z 202.2 (MH + ,100%),204.1 (MH + ,35%). Analysis calcd for C 8 H 12 ClN 3 O: C,47.65; H,6.00; N,20.84. Found: C,47.42; H,6.03; N,21.10%. 6-chloro-1-(2-methoxyethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (102):diamine 101 (0.99 g, 4.90 mmol) was dried in MeCN CDI (0.96 g, 5.89 mmol) was added to a stirred solution in (50 ml) at 20°C. The mixture was stirred at 20°C for 48 hours. Evaporate the solvent and dissolve the residue in CHCl 3 (100 mL) and water (100 mL). The organic fraction was washed with water (2 x 50 mL), brine (50 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was precipitated from 50% EtOAc / petroleum ether to give pyridinone 102 (0.75 g, 67%) as a white powder. mp 170-171 °C; 1 H NMR (CDCl 3 ) δ 9.52 (br s,1 H,3-H),8.10 (d,J = 0.5 Hz,1 H,H-4),7.12 (d,J = 0.5 Hz,1 H,H-7),4.03 (dd,J = 5.2,4.9 Hz,2 H,H-2'),3.68 (dd,J = 5.2,4.9 Hz,2 H,H-1'),3.34 (s,3 H,2'-OCH 3); MS m / z 228.1 (MH + ,100%),230.1 (MH + ,35%).Anal calcd for C 9 H 10 ClN 3 O 2 : C,47.49; H,4.43; N,18.46. Found: C,47.54; H,4.28; N,18.57%. 6-chloro-1-(2-methoxyethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (103):pyridinone 102 (0.72g, 3.16mmol ) and MeI (0.30 ml, 4.74 mmol) in dry DMF (20 ml) was added NaH (60% dispersion, 152 mg, 3.80 mmol) at 5°C. The mixture was stirred at 20° C. for 16 hours and then quenched with ice / water (5 mL). The solvent was evaporated and the residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give chloride 103 (0.43 g, 56%) as a white powder. mp (DCM) 80-82 °C; 1 H NMR (CDCl 3 ) δ 7.96 (s,1 H,H-4),7.09 (d,J = 0.5 Hz,1 H,H-7),4.02 (dd,J = 5.3,4.9 Hz,1 H,H-2') ,3.65 (dd,J = 5.2,4.9 Hz,2 H,H-1'),3.45 (s,3 H,3-CH 3 ),3.34 (s,3 H,2’-OCH 3 ); MS m / z 242.2 (MH + ,100%),244.1 (MH + ,35%).Anal calcd for C 10 H 12 ClN 3 O 2 ·0.1CH 2 Cl 2 : C,48.49; H,4.92; N,116.80 Found: C,48.66; H,4.95; N,16.89%. 6-((4-methoxy-2-methylphenyl)amino)-1-(2-methoxyethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (104): Chloride 103 (117 mg, 0.48 mmol), Aniline (80 mg, 0.58 mmol), Pd 2 dba 3 (22 mg, 24 μmol), XPhos (46 mg, 96 μmol), and Cs 2 C.O. 3 A degassed mixture of (344 mg, 1.06 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 104 (84 mg, 51%) as white needles, eluting with EtOAc / petroleum ether. mp (EtOAc / pet ether) 133-135 °C; 1 H NMR (CDCl 3 ) δ 7.74 (d,J = 0.4 Hz,1 H,H-4),7.22 (d,J = 8.6 Hz,1 H,H-6''),6.83 (d,J = 2.9 Hz,1 H, H-3''),6.76 (dd,J = 8.6,2.9 Hz,1 H,H-5''),6.15 (d,J = 0.4 Hz,1 H,H-7),5.98 (s,1 H,6-NH),3.88 (t,J = 5.3 Hz,1 H,H-2'),3.82 (s,3 H,4''-OCH 3 ),3.57 (t,J = 5.3 Hz,2 H,H-1’),3.39 (s,3 H,3-CH 3 ),3.26 (s,3 H,2’-OCH 3 ),2.24 (s,3 H,2''-CH 3 ); MS m / z 343.2 (MH + ,100%).Anal calcd for C 18 H 22 N 4 O 3 : C,63.14; H,6.48; N,16.36. Found: C,63.25; H,6.38; N,16.45%. HPLC purity 99.8%.

[0388] Example 90: SN39551 6-((4-chloro-2-methylphenyl)amino)-1-(2-methoxyethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]pyridine -2-on(105) [ka] Chloride 103 (110 mg, 0.46 mmol), 4-chloro-2-methylaniline (77 mg, 0.55 mmol), Pd 2 dba 3 (21 mg, 23 μmol), XPhos (44 mg, 92 μmol), and Cs 2 C.O. 3 A degassed mixture of (330 mg, 1.01 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography (80-100% EtOAc / petroleum ether) to give imidazopyridinone 105 (107 mg, 68%) as a milky white powder. mp (EtOAc / pet ether) 92-95 °C; 1 H NMR (CDCl 3 ) δ 7.79 (d,J = 0.6 Hz,1 H,H-4),7.36 (d,J = 8.5 Hz,1 H,H-6''),7.22 (d,J = 2.5 Hz,1 H, H-3''),7.15 (dd,J = 8.5,2.5 Hz,1 H,H-5''),6.47 (d,J = 0.6 Hz,1 H,H-7),6.08 (s,1 H,6-NH),3.94 (dd,J = 5.3,5.0 Hz,2 H,H-2'),3.61 (dd,J = 5.3,5.0 Hz,2 H,H-1'),3.41 (s ,3H,2'-OCH 3 ),3.30 (s,3 H,3-CH 3 ),2.26 (s,3 H,2''-CH 3 ); MS m / z 347.1 (MH + ,100%),349.2 (MH + ,35%).HRMS calcd for C 17 H 20 35 ClN 4 O 2 (MH + ) m / z 347.1269,found 347.1276 (-1.9 ppm); calcd for C 17 H 20 37 ClN 4 O 2 (MH + ) m / z 349.1246,found 349.1249 (-1.0 ppm). HPLC purity 96.9%.

[0389] Example 91: SN39887 6-((4-methoxy-2-methylphenyl)amino)-3-methyl-1-(oxetan-3-yl)-1,3-dihydro-2H-imidazo[4,5-c] Pyridin-2-one(110) [ka] 2-chloro-5-nitro-N-(oxetan-3-yl)pyridin-4-amine (106): nitropyridine 2 (0.87 g, 4.50 mmol) and iPr 2 To a stirred solution of NEt (1.18 mL, 6.75 mmol) in dry DCM (5 mL) was added dropwise a solution of oxetan-3-amine (0.36 g, 5.0 mmol) in dry DCM (5 mL) at 5°C. The mixture was stirred at 20 °C for 16 h, then diluted with DCM (100 ml), washed with water (3 x 50 ml) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (20-40%) of EtOAc / petroleum ether to give chloride 106 (1.17 g, 90%) as a yellow powder. mp 139-141 °C; 1 H NMR (CDCl 3 ) δ 9.06 (s,1 H,H-6),8.52 (br s,1 H,4-NH),6.42 (s,1 H,H-3),5.08 (dd,J = 7.2,6.7 Hz, 2 H,H-2',H-4'),4.73-4.78 (m,1 H,H-3'),4.67 (dd,J = 6.4,6.2 Hz,2 H,H-2',H- 4'); MS m / z 230.1 (MH + ,100%),232.0 (MH + ,35%); HRMS calcd for C 8 H 9 35 ClN 3 O 3 (MH +) m / z 230.0327,found 230.0321 (2.5 ppm). 6-chloro-N 4 -(oxetan-3-yl)pyridine-3,4-diamine(107):SnCl 2 ·2H 2 To a solution of O (4.60 g, 20.4 mmol) in EtOAc (100 ml) was added dropwise a solution of nitropyridine 106 (1.17 g, 5.10 mmol) in EtOAc (50 ml) at a temperature below 60 °C. After stirring for 2 hours, it was cooled to 5°C and concentrated (solution). N.H. 3 The solution was added until the solution was basic (pH 9). The resulting precipitate was filtered and washed with EtOAc (100 mL). The combined organic fractions were dried (MgSO 4 ), filtered and evaporated the solvent to give diamine 107 (1.01 g, 99%) as a white powder. mp 183-186 °C; 1 H NMR [(CD 3 ) 2 SO] δ 7.25 (s,1 H,H-2),6.71 (br s,1 H,3-NH 2 ),6.34 (s,1 H,H-5),5.57 (br s,1 H,3-NH 2 ),3.33-3.40 (m,4 H,4-NH,H-2',H-3',H-4'),3.13 (dt,J = 9.1,2.3 Hz,1 H,H-2') ,2.95 (ddd,J = 11.1,4.7,2.0 Hz,1 H,H-4'); MS m / z 200.1 (MH + ,100%),202.1 (MH + ,35%); HRMS calcd for C 8 H 11 35 ClN 3 O (MH + ) m / z 200.0585,found 200.0589 (-2.1 ppm). Drying of 6-chloro-1-(oxetan-3-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (108):diamine 107 (1.00 g, 5.01 mmol) To a stirred solution in MeCN (50ml) was added CDI (0.97g, 6.00mmol) at 20°C. The mixture was stirred at 20°C for 96 hours. Evaporate the solvent and dissolve the residue in CHCl 3 (150 mL) and water (100 mL). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (80-100%) of EtOAc / petroleum ether to give pyridinone 108 (0.24 g, 22%) as white crystals. mp 234 °C (decomp); 1 H NMR [(CD 3 ) 2 SO] δ 7.74 (s,1 H,H-4),7.69 (s,1 H,H-7),6.55 (br d,J = 4.0 Hz,1 H,3-NH),4.60-4.67 (m ,1 H,H-3'),4.12-4.22 (m,2 H,H-2',H-4'),3.62 (ddd,J = 11.4,4.3,3 1Hz,1 H,H-2' ),3.97-3.05 (m,1 H,H-4'); MS m / z 226.1 (MH + ,100%),228.1 (MH + ,35%); HRMS calcd for C 9 H 9 35 ClN 3 O 2 (MH + ) m / z 226.0378,found 226.0374 (1.8 ppm). 6-chloro-3-methyl-1-(oxetan-3-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (109):Pyridinone 108 (0.30g, 1.33 NaH (60% dispersion, 64 mg, 1.60 mol) was added to a stirred solution of MeI (0.12 ml, 2.00 mol) in dry DMF (10 ml) at 5°C. The mixture was stirred at 20° C. for 16 hours and then quenched with ice / water (5 mL). The solvent was evaporated and the residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give chloride 109 (0.16 g, 49%) as a white powder. mp 192-194 °C; 1 H NMR (CDCl 3 ) δ 7.98 (s,1 H,H-4),7.75 (s,1 H,H-7),4.66 (t,J = 8.6 Hz,1 H,H-2'),4.34-4.43 (m, 1 H,H-3''),4.12 (t,J = 8.6 Hz,1 H,H-4'),3.47 (dd,J = 11.1,3.3 Hz,1 H,H-2'),3.15 ( dd,J = 11.1,9.7 Hz,1 H,H-4'),3.00 (s,3 H,3-CH 3 ); MS m / z 240.0 (MH + ,100%),242.0 (MH + ,35%); HRMS calcd for C 10 H 11 35 ClN 3 O 2 (MH + ) m / z 240.0534,found 240.0543 (-3.7 ppm). 6-((4-methoxy-2-methylphenyl)amino)-3-methyl-1-(oxetan-3-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2- On (110): Chloride 109 (148 mg, 0.62 mmol), 4-methoxy-2-methylaniline (102 mg, 0.74 mmol), Pd 2 dba 3 (28 mg, 31 μmol), XPhos (59 mg, 124 μmol), and Cs 2 C.O. 3 A degassed mixture of (444 mg, 1.36 mmol) in MeCN (10 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 110 (101 mg, 48%) as a pink foam, eluting with EtOAc. mp (EtOAc / pet ether) 77-80 °C; 1 H NMR (CDCl 3 ) δ 7.63 (s,1 H,H-4),7.31 (s,1 H,H-7),7.30 (d,J = 8.6 Hz,1 H,H-6''),6.78 (d,J = 2.9 Hz,1 H,H-3''),6.74 (dd,J = 8.6,2.9 Hz,1 H,H-5''),5.81 (s,1 H,6-NH),4.58 (t ,J = 8.6 Hz,1 H,H-2' or H-4'),4.38 (dq,J = 8.5,3.1 Hz,1 H,1-CH),4.05 (t,J = 8.6 Hz,1 H ,H-2' or H-4'),3.81 (s,3 H,4''-OCH 3 ),3.33 (dd,J = 10.9,3.2 Hz,1 H,H-2' or H-4'),3.00 (dd,J = 10.8,10.0 Hz,1 H,H-2' or H-4' ),2.90 (s,3 H,3-CH 3 ),2.24 (s,3 H,2''-CH 3 ); MS m / z 341.2 (MH + ,100%); HRMS calcd for C 18 H 21 N 4 O 3 (MH + ) m / z 341.1608,found 341.1612 (-1.0 ppm). HPLC purity 98.0%.

[0390] Example 92: SN39878 6-((4-methoxy-2-methylphenyl)amino)-3-methyl-1-(tetrahydrofuran-3-yl)-1,3-dihydro-2H-imidazo[4,5-c] Pyridin-2-one(115) [ka] 2-Chloro-5-nitro-N-(tetrahydrofuran-3-yl)pyridin-4-amine (111): Nitropyridine 2 (1.17 g, 6.02 mmol) and tetrahydrofuran-3-amine with HCl (0.78 g, 6.3 mmol) ) in a stirred solution in dry DCM (80 ml) with iPr 2 NEt (2.62 mL, 15.1 mmol) was added dropwise at 5°C. The mixture was stirred at 20 °C for 16 h, then diluted with DCM (100 ml), washed with water (3 x 50 ml) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (40-50%) of EtOAc / petroleum ether to give chloride 111 (1.37 g, 93%) as yellow crystals. mp 132-134 °C; 1 H NMR (CDCl 3) δ 9.03 (s,1 H,H-6),8.27 (br s,1 H,4-NH),6.73 (s,1 H,H-3),4.18-4.25 (m,1 H,H- 3'),4.00-4.08 (m,2 H,H-2'),3.93 (ddd,J = 8.8,8.6,5.4 Hz,1 H,H-5'),3.84 (dd,J = 9.7,2.8 MS m / z 244.1 (MH + ,100%),246.1 (MH + ,35%); HRMS calcd for C 9 H 11 35 ClN 3 O 3 (MH + ) m / z 244.0484,found 244.04387(-1.3 ppm). 6-chloro-N 4 -(tetrahydrofuran-3-yl)pyridine-3,4-diamine(112):SnCl 2 ·2H 2 To a stirred solution of O (5.05g, 22.4mmol) in EtOAc (100ml) was added dropwise a solution of nitropyridine 111 (1.36g, 5.80mmol) in EtOAc (50ml) at a temperature below 60°C. The mixture was stirred at 60°C for 2 hours, then cooled to 5°C and concentrated (solution). N.H. 3 The solution was added until the solution was basic (pH 9). The resulting precipitate was filtered and washed with EtOAc (100 mL). The combined organic fractions were dried (MgSO 4 ), filtered and evaporated to give diamine 112 (1.17 g, 94%) as a white powder. 1 H NMR [(CD 3 ) 2 SO] δ 7.66 (s,1 H,H-2),6.43 (s,1 H,H-5),4.46 (br d,J = 5.3 Hz,1 H,3-NH),4.04-4.10 (m ,1 H,H-3'),3.94-4.02 (m,2 H,H-2'),3.88 (dt,J = 8.6,5.4 Hz,1 H,H-5'),3.78 (dd,J = 9.4,2.4 Hz,1 H,H-5'),3.04 (br s,2 H,4-NH 2 ),2.29-2.38 (m,1 H,H-4’),1.87-1.95 (m,1 H,H-4’); MS m / z 214.1 (MH + ,100%),216.1 (MH + ,35%); HRMS calcd for C 9 H 13 35 ClN 3 O (MH + ) m / z 214.0742,found 214.0739 (1.2 ppm). Drying of 6-chloro-1-(tetrahydrofuran-3-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (113):diamine 112 (0.48 g, 2.25 mmol) To a stirred solution in MeCN (50ml) was added CDI (0.44g, 2.71mmol) at 20°C. The mixture was stirred at 20°C for 96 hours. Evaporate the solvent and dissolve the residue in CHCl 3 (150 mL) and water (100 mL). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was precipitated from 50% EtOAc / petroleum ether to give pyridinone 113 (0.45 g, 83%) as a white powder. mp 254-256 °C; 1 H NMR [(CD 3 ) 2 SO] δ 11.42 (br s,1 H,3-H),7.97 (s,1 H,H-4),7.28 (s,1 H,H-7),5.02-5.10 (m,1 H,H -3'),4.18 (dt,J = 8.5,4.3 Hz,1 H,H-5'),3.98 (dd,J = 9.9,3.6 Hz,1 H,H-2'),3.82 (dd,J = 9.9,7.5 Hz,1 H,H-2'),3.66 (q,J = 8.3 Hz,1 H,H-5'),2.27-2.40 (m,1 H,H-4'),2.00- 2.10 (m,1 H,H-4'); MS m / z 240.1 (MH + ,100%),242.1 (MH + ,35%); HRMS calcd for C 10 H 11 35 ClN 3 O 2 (MH + ) m / z 240.0534,found 240.0535 (-0.3 ppm). 6-chloro-3-methyl-1-(tetrahydrofuran-3-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (114):Pyridinone 113 (0.76g, 3.15 To a stirred solution of MeI (0.29 mL, 4.73 mmol) in dry DMF (10 mL) was added NaH (60% dispersion, 151 mg, 3.78 mmol) at 5 °C. The mixture was stirred at 20° C. for 16 hours and then quenched with ice / water (5 mL). The solvent was evaporated and the residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give chloride 114 (0.54 g, 68%) as a white powder, eluting with EtOAc. mp 154-156 °C; 1 H NMR (CDCl 3 ) δ 8.00 (s,1 H,H-4),7.32 (d,J = 0.4 Hz,1 H,H-7),5.23-5.29 (m,1 H,H-3'),4.33 (dt, J = 8.8,3.5 Hz,1 H,H-5'),4.09 (dd,J = 10.4,3.0 Hz,1 H,H-2'),3.92 (dd,J = 10.4,7.5 Hz,1 H, H-2'),3.76 (dt,J = 9.2,7.4 Hz,1 H,H-5'),3.45 (s,3 H,3-CH 3 ),2.42-2.52 (m,1 H,H-4’),2.03-2.14 (m,1 H,H-4’); MS m / z 254.0 (MH + ,100%),256.0 (MH + ,35%); HRMS calcd for C 11 H 13 35 ClN 3 O 2 (MH + ) m / z 254.0691,found 254.0686 (1.9 ppm). 6-((4-methoxy-2-methylphenyl)amino)-3-methyl-1-(tetrahydrofuran-3-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridine-2- On (115): Chloride 114 (112 mg, 0.41 mmol), 4-methoxy-2-methylaniline (73 mg, 0.53 mmol), Pd 2 dba 3 (19mg, 21μmol), XPhos (39mg, 82μmol), and Cs 2 C.O. 3 A degassed mixture of (294 mg, 0.90 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 115 (104 mg, 66%) as a tan foam, eluting with EtOAc. mp 113-116 °C; 1 H NMR [(CD 3 ) 2 SO] δ 7.78 (s,1 H,H-4),7.73 (s,1 H,6-NH),7.27 (d,J = 8.7 Hz,1 H,H-6''),6.79 (d, J = 2.9 Hz,1 H,H-3''),6.70 (dd,J = 8.7,2.9 Hz,1 H,H-5''),6.51 (s,1 H,H-7),5.00- 5.07 (m,1 H,H-3'),4.04 (dt,J = 8.5,4.4 Hz,1 H,H-5'),3.88 (dd,J = 9.7,4.0 Hz,1 H,H-2 ),3.80 (dd,J = 9.7,7.6 Hz,1 H,H-2'),3.72 (s,3 H,4''-OCH 3 ),3.66 (q,J = 8.2 Hz,1 H,H-5’),3.35 (s,3 H,3-CH 3 ),2.25-2.35 (m,1 H,H-4’),2.16 (s,3 H,2’’-CH 3 ),2.00-2.08 (m,1 H,H-4’); MS m / z 355.2 (MH + ,100%); HRMS calcd for C 19 H 23 N 4 O 3 (MH + ) m / z 355.1765,found 355.1785 (-5.7 ppm). HPLC purity 99.4%.

[0391] Example 93: SN39881 6-((4-chloro-2-methylphenyl)amino)-3-methyl-1-(tetrahydrofuran-3-yl)-1,3-dihydro-2H-imidazo[4,5-c] Pyridin-2-one(116) [ka] Chloride 114 (118 mg, 0.47 mmol), 4-chloro-2-methylaniline (79 mg, 0.56 mmol), Pd 2 dba 3 (21 mg, 23 μmol), XPhos (44 mg, 93 μmol), and Cs 2 C.O. 3 A degassed mixture of (333 mg, 1.02 mmol) in MeCN (8 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography to give imidazopyridinone 116 (134 mg, 80%) as a white powder, eluting with EtOAc. mp (EtOAc / pet ether) 153-156 °C; 1 H NMR [(CD 3 ) 2 SO] δ 7.94 (s,1 H,H-4),7.87 (s,1 H,6-NH),7.65 (d,J = 8.7 Hz,1 H,H-6''),7.21 (d, J = 2.6 Hz,1 H,H-3''),7.13 (dd,J = 8.7,2.6 Hz,1 H,H-5''),6.79 (s,1 H,H-7),5.03- 5.10 (m,1 H,H-3'),4.13 (dt,J = 8.5,4.3 Hz,1 H,H-5'),3.92 (dd,J = 9.7,4.1 Hz,1 H,H-2 '),3.84 (dd,J = 9.7,7.7 Hz,1 H,H-2'),3.69 (q,J = 8.2 Hz,1 H,H-5'),3.28 (s,3 H,3- CH 3 ),2.27-2.37 (m,1 H,H-4’),2.22 (s,3 H,2’’-CH 3 ),2.02-2.12 (m,1 H,H-4’); MS m / z 359.2 (MH + ,100%),MS m / z 361.2 (MH + ,35%); HRMS calcd for C 18 H 20 35 ClN 4 O 2 (MH + ) m / z 359.1269,found 359.1290 (-5.7 ppm). HPLC purity 94.4%.

[0392] Example 94: SN39536 6-((4-methoxy-2-methylphenyl)amino)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4, 5-c]pyridin-2-one(121) [ka] (2)2,4-dichloro-5-nitropyridine (2): <!--13960-->4-Chloro-5-nitropyridin-2-ol (5.38g, 30.8mmol), POCl 3 (60ml) and tetramethylammonium chloride (10.1g, 32.5mmol) was stirred at 120°C for 3 hours. The mixture was cooled, poured onto ice / water (500ml) and mixed for 1 hour at 0-10°C. The mixture was extracted with DCM (3 x 100 mL) and the combined organic extracts (MgSO 4 ) dried. The solution was filtered through a neutral alumina column and washed with DCM (50 mL). Evaporation of the solvent gave nitropyridine 2 (5.43 g, 91%) as a clear oil. 1 H NMR (CDCl 3 ) δ 8.97 (s, 1 H, H-6), 7.59 (s, 1 H, H-3); MS m / z 192.9 (MH + , 100%), 194.9 (MH + , 70%). 2-chloro-5-nitro-N-(tetrahydro-2H-pyran-4-yl)pyridin-4-amine (117): Nitropyridine 2 (1.00 g, 5.18 mmol) and iPr 2 To a stirred solution of NEt (1.15 mL, 6.22 mmol) in dry DCM (5 mL) was added a solution of tetrahydro-2H-pyran-4-amine (0.55 g, 5.4 mmol) in dry DCM (5 mL) at 5 °C. dripped. The mixture was stirred at 20 °C for 16 h, then diluted with DCM (100 ml), washed with water (3 x 50 ml) and dried (MgSO 4 ) and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (30-50%) of EtOAc / petroleum ether to give chloride 117 (1.12 g, 84%) as a yellow needle. mp 169-171 °C; 1 H NMR (CDCl 3 ) δ 9.04 (s,1 H,H-6),8.19 (br s,1 H,4-NH),6.75 (s,1 H,H-3),4.04 (ddd,J = 12.0,3.8,3.6 Hz,2 H,H-2',H-6'),3.65-3.76 (m,1 H,H-4'),3.58 (dt,J = 10.9,2.3 Hz,2 H,H-2', H-6'),2.06 (br d,J = 11.6 Hz,2 H,H-3',H-5'),1.70 (ddd,J = 10.5,4.2,3.0 Hz,2 H,H-3' ,H-5'); MS m / z 256.0 (MH + ,100%),258.0 (MH + ,35%); HRMS calcd for C 10 H 13 35 ClN 3 O 3 (MH + ) m / z 256.0640,found 256.0638 (0.8 ppm). 6-chloro-N 4 -(Tetrahydro-2H-pyran-4-yl)pyridine-3,4-diamine(118):SnCl 2 ·2H 2 To a stirred solution of O (3.78g, 16.8mmol) in EtOAc (100ml) was added dropwise a solution of nitropyridine 117 (1.08g, 4.19mmol) in EtOAc (30ml) maintaining the temperature below 60°C. The mixture was stirred at 60°C for 2 hours, then cooled to 5°C and concentrated (solution). N.H. 3 The solution was added until the solution was basic (pH 9). The resulting precipitate was filtered and washed with EtOAc (100 mL). The combined organic fractions were dried (MgSO 4 ), filtered and evaporated the solvent to give diamine 118 as a white powder. mp 139-141 °C; 1 H NMR [(CD 3 ) 2 SO] δ 7.67 (s,1 H,H-2),6.46 (s,1 H,H-5),4.27 (br d,J = 6.8 Hz,1 H,4-NH),4.03 (ddd,J = 11.7,3.6,3.3 Hz,2 H,H-2',H-6'),3.46-3.57 (m,3 H,H-2',H-4',H-6'),2.99 (br s,2H,3-NH 2 ),2.02 (br d,J = 12.4 Hz,2 H,H-3',H-5'),1.50-1.61 (m,2 H,H-3',H-5'); MS m / z 228.1 (MH + ,100%),230.1 (MH + ,35%); HRMS calcd for C 10 H 15 35 ClN 3 O (MH + ) m / z 228.0898,found 258.0896 (1.1 ppm). Anal. calcd for C 10 H 14 ClN 3 O·1 / 4EtOAc: C,52.91; H,6.46; N,16.83. Found: C,52.91; H,6.58; N,16.90%. 6-chloro-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (119):Diamine 118 (0.94g, 4.13 CDI (0.74 g, 4.54 mmol) was added at 20° C. into a stirred solution of 4.0 mmol) in dry MeCN (50 ml). The mixture was stirred at 20°C for 96 hours. Evaporate the solvent and dissolve the residue in CHCl 3 (150 mL) and water (100 mL). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was precipitated from 50% EtOAc / petroleum ether to give pyridinone 119 (0.83 g, 84%) as a white powder. mp 281-283 °C; 1 H NMR (CDCl 3 ) δ 9.13 (br s,1 H,3-H),8.13 (s,1 H,H-4),7.19 (s,1 H,H-7),4.54 (tt,J = 12.5,4.4 Hz, 1 H,H-4'),4.17 (dd,J = 11.7,4.6 Hz,2 H,H-2',H-6'),3.56 (dt,J = 12.0,1.8 Hz,2 H,H- 2',H-6'),2.40 (dq,J = 12.6,4.6 Hz,2 H,H-3',H-5'),1.86 (ddd,J = 12.6,3.9,1.3 Hz,2 H, H-3',H-5'); MS m / z 254.1 (MH + ,100%),256.1 (MH + ,35%).Anal calcd for C 11 H 12 ClN 3 O 2: C,52.08; H,4.77; N,16.56. Found: C,52.16; H,4.77; N,16.23%. 6-chloro-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (120):Pyridinone 119( To a stirred solution of MeI (0.86 g, 3.39 mmol) and MeI (0.32 mL, 5.09 mmol) in dry DMF (20 mL) was added NaH (60% dispersion, 163 mg, 4.07 mmol) at 5 °C. The mixture was stirred at 20° C. for 16 hours and then quenched with ice / water (5 mL). The solvent was evaporated and the residue was partitioned between EtOAc (100ml) and water (50ml). The organic fraction was washed with water (2 x 50 ml), brine (50 ml) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (50-100%) of EtOAc / petroleum ether to give chloride 120 (0.43 g, 47%) as white crystals. mp 190-192 °C; 1 H NMR (CDCl 3 ) δ 7.99 (s,1 H,H-4),7.15 (d,J = 0.5 Hz,1 H,H-7),4.54 (tt,J = 12.5,4.4 Hz,1 H,H-4') ,4.15 (dd,J = 11.7,4.7 Hz,2 H,H-2',H-6'),3.55 (dt,J = 12.0,1.9 Hz,2 H,H-2',H-6') ,3.45 (s,3H,3-CH 3 ),2.38 (dq,J = 12.5,4.7 Hz,2 H,H-3',H-5'),1.77 (ddd,J = 12.4,4.0,1.5 Hz,2 H,H-3',H- 5'); MS m / z 268.0 (MH + ,100%),270.0 (MH + ,35%); HRMS calcd for C 12 H 15 35 ClN 3 O 2 (MH + ) m / z 268.0847,found 268.0854 (-2.6 ppm). 6-((4-methoxy-2-methylphenyl)amino)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4,5-c] Pyridin-2-one (121): chloride 120 (125 mg, 0.47 mmol), aniline (77 mg, 0.56 mmol), Pd 2 dba 3 (21 mg, 24 μmol), XPhos (45 mg, 94 μmol), and Cs 2 C.O. 3 A degassed mixture of (337 mg, 1.03 mmol) in MeCN (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered through diatomaceous earth and the filtrate was evaporated. The residue was partitioned between EtOAc (50ml) and water (50ml). The organic fraction was washed with water (30 mL), brine (30 mL) and dried (MgSO 4 ), filtered and the solvent was evaporated. The residue was purified by chromatography eluting with a gradient (80-100%) of EtOAc / petroleum ether to give imidazopyridinone 121 (122 mg, 70%) as pink crystals. mp (EtOAc / pet ether) 176-178 °C; 1 H NMR (CDCl 3 ) δ 7.77 (s,1 H,H-4),7.25 (d,J = 8.6 Hz,1 H,H-6''),6.85 (d,J = 2.9 Hz,1 H,H-3'' ),6.78 (dd,J = 8.6,2.9 Hz,1 H,H-5''),6.24 (d,J = 0.5 Hz,1 H,H-7),5.95 (s,1 H,6-NH ),4.41 (tt,J = 12.4,4.2 Hz,1 H,H-4'),4.07 (dd,J = 11.6,4.4 Hz,2 H,H-2',H-6'),3.83 (s ,3H,4''-OCH 3 ),3.50 (dt,J = 12.0,1.6 Hz,2 H,H-2’,H-6’),3.38 (s,3 H,3-CH 3 ),2.20-2.33 (m,5 H,2''-CH 3 ,H-3’,H-5’),1.69 (dd,J = 12.4,2.4 Hz,2 H,H-3’,H-5’); MS m / z 369.2 (MH + ,100%).Anal calcd for C 20 H 24 N 4 O 3 ·1 / 4EtOAc: C,64.60; H,6.71; N,14.35. Found: C,64.76; H,6.74; N,14.48%. HPLC purity 99.4%.

[0393] Example 95: SN39537 6-((4-chloro-2-methylphenyl)amino)-3-methyl-1-(tetrahydro-2-pyran-4-yl)-1,3-dihydro-2-imidazo[4, 5-c]pyridin-2-one(122) [ka] Chloride 120 (107mg, 0.40mmol), 4-chloro-2-methylaniline (68mg, 0.48mmol), Pd 2 dba 3 (18mg, 20μmol), XPhos (38mg, 80μmol), and Cs 2 C.O. 3 A degassed mixture of (287 mg, 0.88 mmol) in dioxane (6 mL) was stirred in a sealed tube at 120 °C for 16 h. The mixture was cooled, diluted with EtOAc (30 mL), filtered th...

Claims

1. Compounds of Formula I: 【Chemical 1】 or a pharmaceutically acceptable salt or solvate thereof (where, X is selected from the group consisting of (a), (b), and (c): (a) -H; (b) -OH、-ハロ、-OR １ 、-OC(O)H、-OC(O)R １ 、-OC(O )NH ２ -OC(O)NHR １ 、 -OOOOOOO １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、-NHC(O)H、 -NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ -NHC(O)NR １ R １ 、 -NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、-SO ２ NH ２ 、-SO ２ NER １ 、-SO ２ N １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F--&--CO ２ H-. ２ R １ 、-CHO、-C(O)R １ 、-C(O)NH ２ 、 -C(O)NHR １ 、-C(O)NR １ R １ 、-CONNHSO ２ H、-ANHSO ２ R １ 、-CONNR １ SO ２ R １ 、-F、 -(C ３ -C ７ ) cycloalkylamino, imidazolyl, piperazinyl, -(C １ -C ６ )--optionally substituted with one or more groups independently selected from alkylpiperazinyl and morpholinyl-(C １－ C ６ ) alkyl; (c) -OH、-ハロ、-OR １ 、-OC(O)H、-OC(O)R １ 、-OC( O)NH ２ -OC(O)NHR １ 、 -OOOOOOO １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、-NHC(O)H、 -NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ -NHC(O)NR １ R １ 、 -NR １ C(O)EER １ 、-NAC(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、-SO ２ NH ２ 、-SO ２ NER １ 、 -SO ２ NR １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R １ 、-CHO、-C(O)R １ 、-C(O)NH ２ 、 -C(O)NHR １ 、-C(O)NR １ R １ 、-CONNHSO ２ H、-GNHSO ２ R １ 、-CONNR １ SO ２ R １ 、-F、 -(C ３ -C ７ ) cycloalkylamino, imidazolyl, piperazinyl, -(C １ -C ６ )-alkylpiperazinyl and morpholinyl, optionally substituted with one or more groups independently selected from (C ２－ C ６ ) alkenyl; Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ , -CF ３ , -CHF ２ , -CH ２ F, —CN, —CO ２ H, -CO ２ R ２ , -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ or -C(O)NR ２ R ２ -(C １－ C ６ ) alkyl, wherein R ２ Ha-(C １－ C ６ ) alkyl, The -Ph is -(C １－ C ６ ) alkyl, -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ , -CF ３ , -CHF ２ , -CH ２ F, —CN, —CO ２ H, -CO ２ R ２ , -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ and —C(O)NR ２ R ２ and optionally substituted with one or more groups independently selected from the group consisting of R ２ Ha-(C １－ C ６ ) alkyl, Y is selected from the group consisting of the following (c) to (e): (c)-R １ 、-OH、-ハロ、-OR １ 、-OC(O)H,OC(O)R １ 、-OC ((O)NH) ２ 、 -OCOOOOO １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、 -NHC(O)H、-NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ 、 -NFCOOOO １ R １ 、-NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、 -SO ２ NH ２ 、-SO ２ NHR １ 、-SO ２ NR １ R １ 、-CF ３ 、-CHF ２ 、-C H ２ F、-CN、-CO ２ H、-CO ２ R １ 、-CHO、 -C(O)R １ 、-C(O)NH ２ 、-C(O)NHR １ 、-C(O)NR １ R １ 、-CONHSO ２ H、-CONHSO ２ R １ 、and -CONR １ SO ２ R １ and optionally substituted with one or more groups independently selected from -(C ３－ C ７ ) cycloalkyl; Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ ,- CHO、-C(O)R ２ 、-C(O)NH ２ 、 -C(O)NHR ２ and —C(O)NR ２ R ２ and wherein R ２ Ha-(C １－ C ６ ) alkyl, (d)-R １ 、-OH、-ハロ、-OR １ 、-OC(O)H、-C(O)R １ 、-OC(O)NH ２ 、 -OCOOOOO １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、 -NHC(O)H、-NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ 、 -NFCOOOO １ R １ 、-NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、 -SO ２ NH ２ 、-SO ２ P. １ 、-SO ２ NR １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R １ 、-CHO、 -C(O)R １ , —C(O)NH ２ , —C(O)NHR １ , —C(O)NR １ R １ , -CONHSO ２ H, -CONHSO ２ R １ , and -CONR １ SO ２ R １ -(C ３－ C ７ ) heterocycloalkyl; Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ ,- CHO、-C(O)R ２ 、-C(O)NH ２ 、 -C(O)NHR ２ and —C(O)NR ２ R ２ and wherein R ２ Ha-(C １－ C ６ ) alkyl, (e) -R １ 、-OH、-ハロ、-OR １ 、-OC(O)H,OC(O)R １ ,-OC(O)NH ２ 、 -OCOOOOO １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、 -NHC(O)H、-NHC(O)R １ 、-NRC(O)R １ 、-NHC(O)NH ２ 、-NHC(O)NHR １ 、-NHC(O)NR １ R １ 、 -NR １ C(O)NH ２ 、-NR １ C(O)EER １ 、-NR １ C(O)NH ２ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、 -S(O)R １ ,-SO ２ R １ ,-SO ２ NH ２ ,-SO ２ NHR １ ,-SO ２ NR １ R １ ,-CF ３ ,-CHF ２ ,--H ２ F、-CN、-CO ２ H、 -CO ２ R １ 、-CHO、-C(O)R １ 、-C(O)NH ２ -C(O)NHR １ 、-C(O)NR １ R １ -CONHSO ２ H、 -CONHSO ２ R １ and -CONR １ SO ２ R １ -(C ４－ C ８ ) aryl; Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-O ２ R ２ 、-CHO、-C(O)R ２ 、-C(O)NH ２ 、 -C(O)NHR ２ and —C(O)NR ２ R ２ -(C １－ C ６ ) alkyl, wherein R ２ Ha-(C １－ C ６ ) alkyl, Z is selected from the group consisting of the following (a) and (b): (a)-R １ 、-OH、-ハロ、-OR １ 、-OC(O)H、-OC(O)R １ ,-OC(O)NH ２ 、-OC(O)NHR １ 、 -OOOOOOO １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、-NHC(O)H、 -NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ -NHC(O)NR １ R １ 、 -NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、-SO ２ NH ２ 、 -SO ２ P. １ 、-SO ２ NR １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R １ 、-CHO、-C(O)R １ 、 -C(O)NH ２ , —C(O)NHR １ , —C(O)NR １ R １ , -CONHSO ２ H, -CONHSO ２ R １ , -CONR １ SO ２ R １ , morpholinyl, piperazinyl, pyridinyl, and pyrimidinyl, optionally substituted with one or more groups independently selected from -(C ４－ C ８ ) aryl; Each of the R １ is -(C １－ C ６ ) alkyl and -(C ４ -C ８ ) Independently of the aryl each of said groups is selected from -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ 、-SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、-CHO、-C(O)R ２ , -C(O)NH ２ , —C(O)NHR ２ or -C(O)NR ２ R ２ may be optionally substituted with, and the R ２ Ha-(C １－ C ６ ) alkyl, Each of the morpholinyl, piperazinyl, pyridinyl, and pyrimidinyl is —(C １－ C ６ ) alkyl, -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ 、-SH、-SR ２ 、-SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、-CHO、 -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ and —C(O)NR ２ R ２ and optionally substituted with one or more groups independently selected from the group consisting of R ２ Ha-(C １－ C ６ ) alkyl, (b) -R １ 、-OH、-ハロ、-OR １ 、-OC(O)H、-OC(O)R １ 、- P.S. ２ -OC(O)NHR １ 、 -OOOOOOO １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ -NHR １ -NR １ R １ 、-NHC(O)H、 -NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ -NHC(O)NR １ R １ 、 -NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、-SO ２ NH ２ 、 -SO ２ P. １ 、-SO ２ NR １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R １ 、-CHO、-C(O)R １ 、 -C(O)NH ２ , —C(O)NHR １ , —C(O)NR １ R １ , -CONHSO ２ H, -CONHSO ２ R １ , -CONR １ SO ２ R １ , morpholinyl, and piperazinyl, optionally substituted with one or more groups independently selected from -(C ５－ C １２ ) heteroaryl; Each of the R １ Ha-(C １－ C ６ ) alkyl and -(C ４ -C ８ ) aryl, each of which is independently selected from -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ 、-SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、-CHO、-C(O)R ２ 、 -C(O)NH ２ , —C(O)NHR ２ or -C(O)NR ２ R ２ may be optionally substituted with, ２ Ha-(C １－ C ６ ) alkyl 、 Each of the morpholinyl and piperazinyl is —(C １－ C ６ )alkyl, -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ 、-SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、-CHO、-C(O)R ２ 、 -C(O)NH ２ , —C(O)NHR ２ and —C(O)NR ２ R ２ and optionally substituted with one or more groups independently selected from the group consisting of R ２ Ha-(C １－ C ６ ) alkyl.

2. The compound according to claim 1, wherein X is the following (b), or a pharmaceutically acceptable salt or solvate thereof: ((b) -OH、-ハロ、-OR １ 、-OC(O)H、-OC(O)R １ 、-OC( O)NH ２ -OC(O)NHR １ 、 -OOOOOOO １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、-NHC(O)H、 -NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ -NHC(O)NR １ R １ 、 -NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、-SO ２ NH ２ 、-SO ２ NER １ 、-SO ２ N １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F--&--CO ２ H-. ２ R １ 、-CHO、-C(O)R １ 、-C(O)NH ２ 、 -C(O)NHR １ 、-C(O)NR １ R １ 、-CONNHSO ２ H、-GNHSO ２ R １ 、-CONNR １ SO ２ R １ 、-F、 -(C ３ -C ７ ) cycloalkylamino, imidazolyl, piperazinyl, -(C １ -C ６ )--optionally substituted with one or more groups independently selected from alkylpiperazinyl and morpholinyl-(C １－ C ６ ) alkyl; Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、-CHO、-C(O)R ２ 、-C(O)NH ２ 、 -C(O)NHR ２ or -C(O)NR ２ R ２ -(C １－ C ６ ) alkyl, wherein R ２ Ha-(C １－ C ６ ) alkyl, The -Ph is -(C １－ C ６ ) alkyl, -halo, -OH, -OR ２ , -NO ２ , -NH ２ -NHR ２ -NR ２ R ２ -SH,-SR ２ 、 -SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、-CHO、-C(O)R ２ 、-C(O)NH ２ 、 -C(O)NHR ２ and b-C(O)NR ２ R ２ and R ２ Ha-(C １－ C ６ ) alkyl.

3. 3. The compound of claim 2, or a pharmaceutically acceptable salt or solvate thereof, wherein X is OH or NH. ２ -(C １－ C ６ ) alkyl, or a pharmaceutically acceptable salt or solvate thereof.

4. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt or solvate thereof, wherein Y is -(C ３－ C ７ ) selected from the group consisting of cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, cyclohexanyl, pyrrolidinyl, piperidinyl, and phenyl, each of which is selected from the group consisting of -R １ , -OH, -halo, -OR １ , -OC(O)H, -C(O)R １ , —OC(O)NH ２ , -OCOOOOO １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、 -NHC(O)H、-NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ 、 -NFCOOOO １ R １ 、-NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、 -SO ２ NH ２ 、-SO ２ P. １ 、-SO ２ NR １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R １ 、-CHO、 -C(O)R １ , —C(O)NH ２ , —C(O)NHR １ , —C(O)NR １ R １ , -CONHSO ２ H, -CONHSO ２ R １ and -CONR １ SO ２ R １ and optionally substituted with one or more groups independently selected from Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ ,- CHO、-C(O)R ２ 、-C(O)NH ２ 、 -C(O)NHR ２ and -C(O)NR ２ R ２ -(C １－ C ６ ) alkyl, wherein R ２ Ha-(C １－ C ６ ) alkyl, or a pharmaceutically acceptable salt or solvate thereof.

5. The compound according to claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein Y is -(C ３－ C ７ ) A compound or a pharmaceutically acceptable salt or solvate thereof selected from the group consisting of cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, methoxycyclohexanyl, hydroxycyclohexanyl, aminocyclohexanyl, N-methylaminocyclohexanyl, N,N-dimethylcyclohexanyl, pyrrolidinyl, N-methylpyrrolidinyl, piperidinyl, N-methylpiperidinyl, furanyl, pyrrolyl, pyridinyl, hydroxyphenyl, and methoxyphenyl.

6. 6. The compound according to claim 5, or a pharmaceutically acceptable salt or solvate thereof, wherein Y is selected from the group consisting of 4-methoxycyclohexanyl, 4-hydroxycyclohexanyl, and 4-aminocyclohexanyl.

7. 7. The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from the group consisting of furanyl, thiophenyl, pyrrolyl, pyridinyl, imidazolyl, thiazolyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, purinyl, benzodioxolyl, quinoxalinyl, benzothiazinyl, triazolopyridinyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, and imidazopyridinyl -(C ５－ C １２ ) heteroaryl, each of which is —R １ , -OH, -halo, -OR １ , -OC(O)H, -C(O)R １ , —OC(O)NH ２ , -OCOOOOO １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、-NHYR １ 、-NR １ R １ 、 -NHC(O)H、-NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ 、 -EFC(O)NR １ R １ 、-NR １ C(O)EER １ 、-NR １ C(O)NR １ R １ 、-SH、-SR １ 、-S(O)H、-S(O)R １ 、-SO ２ R １ 、 -SO ２ NH ２ 、-SO ２ P. １ 、-SO ２ NR １ R １ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R １ 、-CHO、 -C(O)R １ , —C(O)NH ２ , —C(O)NHR １ , —C(O)NR １ R １ , -CONHSO ２ H, -CONHSO ２ R １ and -CONR １ SO ２ R １ and optionally substituted with one or more groups independently selected from Each of the R １ is -(C １－ C ６ ) alkyl and -(C ４－ C ８ ) aryl, each of which is independently selected from -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ ,- CHO、-C(O)R ２ 、-C(O)NH ２ 、 -C(O)NHR ２ and —C(O)NR ２ R ２ 、 may be optionally substituted with, ２ Ha-(C １－ C ６ ) alkyl, or a pharmaceutically acceptable salt or solvate thereof.

8. 8. The compound of claim 7, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is (C １－ C ６ ) alkyl-substituted —(C ５－ C １２ ) heteroaryl, or a pharmaceutically acceptable salt or solvate thereof.

9. The compound according to claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is -(C 5-C 12 )heteroaryl substituted with Me, or a pharmaceutically acceptable salt or solvate thereof.

10. The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is (C １－ C ６ ) alkyl-substituted —(C ４－ C ８ ) aryl, or a pharmaceutically acceptable salt or solvate thereof.

11. The compound according to claim 10, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is -(C4-C8)aryl substituted with Me, or a pharmaceutically acceptable salt or solvate thereof.

12. 11. The compound of claim 10, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is R １ , —OH, —OR １ , -halo, -NO ２ , -NH ２ , -NHR １ , -NR １ R １ , -SO ２ R １ and -Bn, wherein R １ (C １－ C ６ ) alkyl, or a pharmaceutically acceptable salt or solvate thereof.

13. The compound according to claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is Me.

14. The compound according to claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is phenyl substituted at the 4-position with -OMe, -Cl, or -OH, or Z is phenyl substituted at the 5-position with -SO ２ R １ and -NO ２ and the phenyl is substituted with any one of the -R １ (C １－ C ６ ) alkyl, or a pharmaceutically acceptable salt or solvate thereof.

15. The compound according to claim 14, or a pharmaceutically acceptable salt or solvate thereof, wherein —R 1 is Me.

16. Compound of Formula II: 【Chemistry 2】 or a pharmaceutically acceptable salt or solvate thereof (wherein X and Y are as defined in claim 1, A １、 A ２ and A ３ is independently selected from CH or N; B １ is -OH, -OR １ , Halo, -NO ２ , -NH ２ , N.H.R. １ , -SO ２ R １ and -OBn, Each R １ is halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ 、-NR ２ R ２ 、-SH、-SR ２ 、-SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、 -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ or -C(O)NR ２ R ２ -(C １－ C ６ ) alkyl, and R ２ Ha-(C １－ C ６ ) alkyl.

17. Compound of Formula III: 【Chemistry 3】 or a pharmaceutically acceptable salt or solvate thereof (wherein X and Y are as defined in claim 1, A １ is N or C. D is selected from N, O, and S; R ３ is H, -(C １－ C ６ ) alkyl, —CO ２ R １ , -CONHR １ and CONHR １ R １ and R １ Ha-(C １－ C ６ ) alkyl.

18. Compound of Formula IV: 【Chemistry 4】 or a pharmaceutically acceptable salt or solvate thereof (wherein X and Y are as defined in claim 1, B ２ and D is independently selected from N, O and S; 【Chemistry 5】 represents a single bond or a double bond, 【Chemistry 6】 is a single bond unless D is N, R ３ is H, -(C １－ C ６ ) alkyl, —CO ２ R １ , -CONHR １ and CONHR １ R １ and R １ Ha-(C １－ C ６ ) alkyl.

19. Compound of Formula V: 【Chemistry 7】 or a pharmaceutically acceptable salt or solvate thereof (wherein X, Y and Z are as defined in claim 1, Pro is, 【Chemistry 8】 wherein * represents the point of attachment to the N atom of formula V. Each of the R １１ is -OH, -halo, -OR １ , -OC(O)H, -OCOOR １ 、-OC(O)NH ２ 、-OC(O)NHR １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、 -NHR １ -NR １ R １ 、-NHC(O)H、-NHC(O)R １ -NRC(O)R １ -NHC(O)NH ２ -NHC(O)NHR １ -NR １ C(O)NH ２ -NHC(O)NR １ R １ -NR １ P.S. １ -NR １ C(O)NR １ R １ -SH,-SR １ 、 -SOOH--OOR １ ,-SO ２ R １ ,-SO ２ NH ２ ,-SO ２ NHR １ ,-SO ２ NR １ R １ ,-CF ３ ,-CHF ２ ,--H ２ F、-CN、-CO ２ H、 -CO ２ R １ 、-CHO、-C(O)R １ 、-C(O)NH ２ -C(O)NHR １ 、-C(O)NR １ R １ -CONHSO ２ H、-CONHSO ２ R １ 、 -CONR １ SO ２ R １ 、-Ph、 -(C ３ -C ７ ) cycloalkylamino, imidazolyl, piperazinyl, -(C １ -C ６ )-alkylpiperazinyl and morpholinyl optionally substituted -(C １－ C ６ ) alkyl, Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ , -CF ３ , -CHF ２ , -CH ２ F, -CN, -CO ２ H, -CO ２ R ２ , -CHO, -C(O)R ２ , -C(O)NH ２ , -C(O)NHR ２ and -C(O)NR ２ R ２ -(C １－ C ６ ) alkyl, wherein R ２ Ha-(C １－ C ６ ) alkyl, The -Ph is -(C １－ C ６ ) alkyl, -halo, -OH, -OR ２ , -NO ２ , -NH ２ -NHR ２ -NR ２ R ２ -SH,-SR ２ 、-SO ２ R ２ 、-SO ２ NH ２ 、-CF ３ 、-CHF ２ 、-CH ２ F、-CN、-CO ２ H、-CO ２ R ２ 、 -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ , —C(O)NR ２ R ２ and wherein said R ２ Ha-(C １－ C ６ ) alkyl, The R １２ and the R １３ are independently selected from the group consisting of -H, -Me and -Et.

20. Compound of Formula VI: 【Chemistry 9】 or a pharmaceutically acceptable salt or solvate thereof (wherein X and Y are as defined in claim 1, E is —O—, —NHCO ２ -, -N(Me)CO ２ -, -COO-, -NH(C １－ C ６ ) alkyl, -O-(C １ -C ６ ) alkyl-N-dimethylamino-, -NH(C １－ C ６ ) alkyl-N-dimethylamino-, -NHCO(C １－ C ６ ) alkyl-N-dimethylamino- and -NHCOCH=CHCH ２ -N-dimethylamino-; Pro is, 【Chemistry 10】 is selected from the group consisting of where * represents the point of attachment to E in formula VI, Each of the R １１ is -OH, -halo, -OR １ , -OC(O)H, -OCOOR １ 、-OC(O)NH ２ 、-OC(O)NHR １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、 -NHR １ 、-NR １ R １ 、-NHC(O)H、-NHC(O)R １ 、-NRC(O)R １ 、-NHC(O)NH ２ 、 -NHC(O)NHR １ ,-PR １ C(O)NH ２ 、-NFC(O)NR １ R １ ,-PR １ C(O)NHR １ ,-PR １ C(O)NR １ R １ ,-EH,-ER １ 、-SOOH、--OOR １ ,-SO ２ R １ ,-SO ２ NH ２ ,-SO ２ NHR １ ,-SO ２ NR １ R １ ,-CF ３ ,-CHF ２ ,--H ２ F、-CN、 -CO ２ H、-CO ２ R １ 、-CHO、-C(O)R １ 、-C(O)NH ２ -C(O)NHR １ 、-C(O)NR １ R １ -CONHSO ２ H、 -CONHSO ２ R １ , -CONR １ SO ２ R １ , -Ph, -(C ３ -C ７ ) cycloalkylamino, imidazolyl, piperazinyl, -(C １ -C ６ )-alkylpiperazinyl and morpholinyl optionally substituted -(C １－ C ６ ) alkyl, Each of the R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ , -CF ３ , -CHF ２ , -CH ２ F, —CN, —CO ２ H, -CO ２ R ２ , -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ or -C(O)NR ２ R ２ -(C １－ C ６ ) alkyl; R ２ Ha-C １ - ６ is alkyl, The -Ph is -(C １－ C ６ ) alkyl, -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ , -CF ３ , -CHF ２ , -CH ２ F, —CN, —CO ２ H, -CO ２ R ２ , -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ and —C(O)NR ２ R ２ and optionally substituted with one or more groups independently selected from the group consisting of R ２ Ha-(C １－ C ６ ) alkyl, The R １２ and the R １３ is independently selected from the group consisting of -H, -Me, and -Et, １４ is -H, -Me, -Et, -OMe, -CF ３ , —CN and ethynyl. However, the above E is -O-(C １ -C ６ ) alkyl-N-dimethylamino-, -NH(C １－ C ６ ) alkyl-N-dimethylamino-, -NHCO(C １－ C ６ ) alkyl-N-dimethylamino- or -NHCOCH=CHCH ２ -N-dimethylamino-, said Pro is 【Chemistry 11】 ).

21. Compound of Formula VII: 【Chemistry 12】 or a pharmaceutically acceptable salt or solvate thereof (wherein X and Z are as defined in claim 1, where J is CH ２ or does not exist, 【Chemistry 13】 is a saturated or unsaturated ring, B ３ is C or N, G is, —O—, —NHCO ２ -, -N(Me)CO ２ -, -COO-, -NH(C １－ C ６ ) alkyl, —O—(C １ -C ６ ) alkyl-N-dimethylamino-, -NH(C １－ C ６ ) alkyl-N-dimethylamino-, -NHCO(C １ -C ６ ) alkyl-N-dimethylamino, and -NHCOCH=CHCH ２ -N-dimethylamino; The Pro is 【Chemistry 14】 is selected from the group consisting of where * represents the point of attachment to G in formula VII, Each R １１ is -OH, -halo, -OR １ , -OC(O)H, -OCOOR １ 、-OC(O)NH ２ 、-OC(O)NHR １ 、-O(A)NR １ R １ 、---------- ２ 、-O?OO)(OR １ ) ２ 、-NH ２ 、 -NHR １ 、-NR １ R １ 、-NHC(O)H、-NHC(O)R １ 、-NRC(O)R １ 、-NHC(O)NH ２ 、 -NHC(O)NHR １ ,-PR １ C(O)NH ２ 、-NFC(O)NR １ R １ ,-PR １ C(O)NHR １ ,-PR １ C(O)NR １ R １ ,-EH,-ER １ 、-SOOH、--OOR １ ,-SO ２ R １ ,-SO ２ NH ２ ,-SO ２ NHR １ ,-SO ２ NR １ R １ ,-CF ３ ,-CHF ２ ,--H ２ F、-CN、 -CO ２ H、-CO ２ R １ 、-CHO、-C(O)R １ 、-C(O)NH ２ -C(O)NHR １ 、-C(O)NR １ R １ -CONHSO ２ H、 -CONHSO ２ R １ , -CONR １ SO ２ R １ , -Ph, -(C ３ -C ７ ) cycloalkylamino, imidazolyl, piperazinyl, -(C １ -C ６ )-alkylpiperazinyl and morpholinyl optionally substituted -(C １－ C ６ ) alkyl, Each of the above R １ -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ , -CF ３ , -CHF ２ , -CH ２ F, —CN, —CO ２ H, -CO ２ R ２ , -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ or -C(O)NR ２ R ２ -(C １－ C ６ ) alkyl, and each R ２ is -C １ - ６ is alkyl, The -Ph is -(C １－ C ６ ) alkyl, -halo, -OH, -OR ２ , -NO ２ , -NH ２ , -NHR ２ , -NR ２ R ２ , -SH, -SR ２ , -SO ２ R ２ , -SO ２ NH ２ , -CF ３ , -CHF ２ , -CH ２ F, —CN, —CO ２ H, -CO ２ R ２ , -CHO, -C(O)R ２ , —C(O)NH ２ , —C(O)NHR ２ and -C(O)NR ２ R ２ and each R ２ Ha-C １ - ６ It is alkyl. The R １２ and the R １３ is independently selected from -H, -Me, and -Et; The R １４ is -H, -Me, -Et, -OMe, -CF ３ , —CN and ethynyl. However, the G is —O—(C １ -C ６ ) alkyl-N-dimethylamino-, -NH(C １－ C ６ ) alkyl-N-dimethylamino-, -NHCO(C １－ C ６ ) alkyl-N-dimethylamino-, or —NHCOCH═CHCH ２ -N － dimethylamino-, said Pro is 【Chemistry 15】 and 【Chemistry 16】 is a saturated ring, ３ is N, B ３ is N, G is -COO-, and B ３ G is —O— if and only if is C.

22. A pharmaceutical composition comprising a compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt or solvate thereof, in combination with one or more pharmaceutically acceptable excipients.

23. 22. A pharmaceutical composition comprising the compound of any one of claims 1 to 21 or a pharmaceutically acceptable salt or solvate thereof, for treating a disease in which inhibition of DNA-PK is beneficial in a subject in need thereof.

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