Imidazo[1,2-a]pyridine compounds and their use in therapeutic applications

Abstract

The present invention relates to compounds of formula (I): and related embodiments [Formula 1] TIFF2023542203000374.tif75170.

Description

[Technical Field]

[0001] (Field of invention) The present invention relates to compounds of formula (I) and salts thereof having activity as inhibitors of N-myristoyltransferase (NMT), particularly its human form. The present invention also relates in particular to the pharmaceutically active use of such compounds in the prevention or treatment of diseases or disorders in which inhibition of N-myristoyltransferase results in therapeutic or preventive effects. Such diseases include hyperproliferative disorders (e.g., B-cell lymphoma and leukemia) and viral infections (e.g., human rhinovirus, HIV, poliovirus, foot and mouth disease, enterovirus 71, and poxvirus infections). Microbial infections (e.g., protozoan infections, e.g., malaria and leishmaniasis, and fungal infections) can also be treated. [Background technology]

[0002] (Background of the invention) N-myristoyltransferase (NMT) is a monomeric enzyme ubiquitous in eukaryotes. NMT catalyzes the irreversible, simultaneous translational transfer of myristic acid (saturated 14-carbon fatty acid) from myristoyl-coenzyme A (myr-CoA), which involves the formation of an amide bond, to a protein substrate containing N-terminal glycine (Farazi, TA, G. Waksman, and J.I. Gordon, J. Biol. Chem., 2001. 276(43): p. 39501-39504). N-myristoylation by NMT follows an ordered Bi-Bi mechanism. Before binding to the protein substrate, Myr-CoA binds to the NMT in the first NMT binding pocket (Rudnick, DA, CA McWherter, WJ Rocque et al., J. Biol. Chem., 1991. 266(15): p. 9732-9739). The bound myr-CoA promotes the opening of the second binding pocket where the protein substrate binds. After binding to the protein substrate, myristate transfer to the protein substrate occurs via a nucleophilic addition-elimination reaction, ultimately releasing CoA and the myristoylated protein.

[0003] There are two types of human NMTs: human NMT1 (HsNMT1) and human NMT2 (HsNMT2). Inhibition of human NMT is effective against various diseases or disorders, such as hyperproliferative disorders (e.g., cancer, e.g., human colorectal cancer, gallbladder cancer, brain tumors, and lymphoma, e.g., B-cell lymphoma) (Resh MD, 1993. Biochern. Biophys. Acta 1115, 307-22; Bertiaume LG, Beuachamp E, WO2017011907), and viral infections, such as HIV (Gottlinger HG, Sodroski JG, Haseltine WA, 1989. Proc. Nat. Acad. Sci. USA 86:5781-85; Bryant ML, Ratner L, 1990. Proc. Natl. Acad. Sci. USA 87:523-27), and human rhinovirus (RV, formerly abbreviated as HRV) (Davis MP, Bottley, References G, Beales LP, Killington, RA, Rowlands DJ, Tuthill, TJ, 2008 Journal of Virology 82 4169-4174; Mousnier A, Bell AS, Swieboda DP, Morales-Sanfrutos J, Perez-Dorado I, Brannigan JA, Newman J, Ritzefeld M, Hutton, JA, Guedan A, Asfor AS, Robinson, SW, Hopkins-Navratilova I, Wilkinson AJ, Johnston SL, Leatherbarrow RJ, Tuthill TJ, Solari R, Tate EW 2018 Nature Chemistry 10(6) 599-606), Corbic Ramljak I, Stanger J, Real-Hohn A. Dreier D, Wimmer L.The literature by Redlberger-Fritz M, Fischl W, Klingel K, Mihovilovic MD, Blaas D, Kowalski H (PLOS Pathogens 14(8): e1007203), and the literature by dengue virus (2019 Microbiology e00831 Suwanmanee S., Mahakhunkijcharoen Y., Ampawong, S., Leaungwutiwong P., Misse, D, Luplertlop, N) have proposed NMTs as targets for the treatment or prevention of dengue virus. Since NMTs play crucial roles in protein transport, mediation of protein-protein interactions, stabilization of protein structure, and signal transduction in biological systems, inhibition of NMT enzymes has the potential to disrupt multiprotein pathways. This is an attractive feature, for example, reducing the risk of resistance development in the treatment or prevention of hyperproliferative disorders and microbial infections.

[0004] Biochemical analyses have shown a high degree of conservation of the myr-CoA binding site, but have demonstrated different peptide bond specificities between human NMT, fungal NMT, and parasitic NMT (Johnson, DR, RS Bhatnagar, JI Gordon et al., Annu. Rev. Biochem., 1994. 63: p. 869-914). As a result, NMT can be considered a target with potential for the development of selective non-peptidogenic inhibitors.

[0005] NMT fungi and mammalian enzymes from various sources have been thoroughly characterized, for example, see the following references: budding yeast (Saccharomyces cerevisiae) (Duronio, RJ, DA Towler, RO Heuckeroth et al., Science, 1989. 243(4892): p. 796-800), Candida albicans (Wiegand, RC, C. Carr, JC Minnerly et al., J. Biol. Chem., 1992. 267(12): p. 8591-8598), and Cryptococcus neoformans (Lodge, JK, RL Johnson, RA Weinberg et al., J. Biol. Chem., 1994. 269(4): p. See also the literature by McIlhinney, RAJ and K. McGlone (2996-3009), human NMT1 (Exp. Cell Res., 1996. 223: p. 348-356), and human NMT2 (Giang, DK and BF Cravatt (J. Biol. Chem., 1998. 273: p. 6595-6598)).

[0006] NMT has also been used to characterize protozoan parasites. For example, see the following references: Plasmodium falciparum (Pf) (Gunaratne, RS, M. Sajid, IT Ling et al., Biochem. J., 2000. 348: p. 459-463), Plasmodium vivax (Pv), Leishmania major (Lm) (Price, HP, MR Menon, C. Panethymitaki et al., J. Biol. Chem., 2003. 278(9): p. 7206-7214), Leishmania donovani (Ld) (Branningan, JA, BA Smith, Z. Yu et al., J. Mol. Biol., 2010. 396: p. See also the literature by Price, HP, MR Menon, C. Panethymitaki et al., J. Biol. Chem., 2003. 278(9): pp. 7206-7214, and Trypanosoma brucei (Tb).

[0007] Several myristoylating proteins have been observed in protozoa, and their functions have been determined. These proteins and the processes they are involved in suggest that N-myristoylation may play a role in numerous pathways in the parasite's ecosystem. Therefore, inhibition of myristoylation can disrupt multiple pathways. Consequently, the likelihood of resistance development should be lower than in the case of some other targets. To date, only a single isoform of NMT has been found in each protozoan organism investigated. If the existence of only a single isoform is correct, this would also help reduce the likelihood of resistance development.

[0008] As described above, NMT has two binding pockets: one is the myr-CoA binding pocket, and the other is the peptide binding pocket. Most NMT inhibitors reported to date target the peptide binding pocket. Most NMT inhibitors developed to date target fungal N-myristoyltransferase.

[0009] Compounds active as inhibitors of NMT have been previously disclosed; see, for example, WO00 / 37464 (Roche), WO2010 / 026365 (University of Dundee), WO2013 / 083991 (Imperial Innovations Limited), WO2017 / 001812 (Imperial Innovations Limited), WO2020 / 128473 (Imperial College Innovations Limited), and WO2020 / 128475 (Imperial College Innovations Limited).

[0010] Furthermore, Bell et al. disclosed the results of a high-throughput screening study conducted to identify inhibitors of NMT, revealing that compounds PF-03531814 (1-(5-chloro-2-{[2-(dimethylamino)ethyl]amino}pyrimidine-4-yl)-N-[(5-methylpyrazine-2-yl)methyl]azetidine-3-carboxamide) and PF-03531549 (1-(5-chloro-2-{[2-(dimethylamino)ethyl]amino}pyrimidine-4-yl)-N-[(2,4-difluorophenyl)methyl]azetidine-3-carboxamide) have more selective activity against Plasmodium falciparum NMT than both human NMTs (PLoS Neglected Tropical Diseases, 2012, 6, e1625). [Table 1]

[0011] There is still a need in the art for further compounds that are active as inhibitors of N-myristoyltransferase, particularly its human form.

Summary of the Invention

[0012] (Summary of the Invention) A compound of formula (I), or a pharmaceutically acceptable ester, amide, carbamate, or salt thereof, which is a salt of such an ester, amide, or carbamate:

Chemical Formula

[0013] The present invention also provides compounds of formula (I), or pharmaceutically acceptable esters, amides, or carbamates thereof, or salts comprising such esters, amides, or carbamates: [ka] (In the formula: n1 is either 1 or 2; n2 is either 1 or 2; X 1 CR x Selected from the group consisting of and N; If present, R x -C is a molecule in which hydrogen, halogen, and one, two, or three substituents, each independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3, are optionally substituted. 1-4 Selected from the group consisting of alkyl groups; R 1 -C is a hydrogen atom; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 Alkyl; and -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -CH3, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups; R 2is hydrogen; -C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -OCH3, and -OCF3 1-4 alkyl; and -C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -CH3, -OCH3, and -OCF3 3-6 selected from the group consisting of cycloalkyl; or R 1 and R 2 together with the atom to which they are attached form a C cycloalkyl group or a 3- to 6-membered non-aromatic heterocyclyl group containing one heteroatom selected from the group consisting of O and N, where the C 3-6 cycloalkyl group or 3- to 6-membered non-aromatic heterocyclyl group is optionally substituted by one or two substituents each independently selected from the group consisting of halogen, -OH, -CH3, -OCH3, and -OCF3; 3-6 R is hydrogen; -C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -OH, -CH3, -OCH3, and -OCF3 3 alkyl; and -C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3 1-4 selected from the group consisting of cycloalkyl; 3-6- or R and R​​​​​​​​​​ If present, R 4 -C is a hydrogen atom; a halogen atom; and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; RANGE-NR a R b Selected from the group consisting of; R 5a and R 5d This includes hydrogen; halogens; methyl molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and methoxy molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; R 5b and R 5c -C is a hydrogen atom; a halogen atom; and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Independently selected from the group consisting of cycloalkyls; Or R 5b and R 5c They are linked together with the atom to which they are bonded so as to form a six-membered aryl group or a five- or six-membered aromatic heterocyclyl group containing one or two heteroatoms selected from the group consisting of S, O, and N, wherein the six-membered aryl group or the five- or six-membered aromatic heterocyclyl group is optionally substituted with one or two substituents, each substituent independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; R 6 is selected from the group consisting of hydrogen and methyl; If present, each R 7 -C 1-4 It is alkyl; R 8 This refers to hydrogen; halogen; -OH; -CN; and -C, which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkyl; -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 3-6 Cycloalkyl; -C alkyl group, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -CN, and methoxy groups optionally substituted with one, two, or three halogens. 1-4 Alkenyls; and -OCs, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Selected from the group consisting of alkyl groups; R 9 -C is a hydrogen atom and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Selected from the group consisting of alkyl groups; or R 8 and R 9They are linked together with the atom to which they are bonded so that they form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms selected from N, O, and S, wherein the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen; -OH; -CN; and -C, where each substituent is optionally substituted with halogen, -OH, and methoxy optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups; p is 0, 1, or 2; Z is a 5- to 13-membered non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and where the 5- to 10-membered non-aromatic heterocyclyl group is optionally substituted with halogens; and each substituent is optionally substituted with halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one, two, three, or four substituents independently selected from the group consisting of alkyl groups; or Z is -NR 10 R 11 And here, R 10 is hydrogen and -C 1-4Selected from the group consisting of alkyl; and R 11 is a 5-10 member non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and wherein the 5-10 member non-aromatic heterocyclyl group is a halogen; -OH; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one, two, three, or four substituents independently selected from the group consisting of alkyl groups; and If present, each R a and R b is hydrogen and -C 1-4 (Independently selected from the group consisting of alkyl groups).

[0014] Surprisingly, the compounds of the present invention were found to have activity as inhibitors of N-myristoyltransferase, and in particular, to be very potent inhibitors of human N-myristoyltransferase 1. Surprisingly, the compounds of the present invention were also found to have good metabolic stability. These advantages make the compounds of the present invention particularly useful for use in the treatment and prevention of diseases in which inhibition of N-myristoyltransferase results in therapeutic or preventive effects, such as hyperproliferative disorders (e.g., B-cell lymphoma and leukemia), viral infections (e.g., human rhinovirus, HIV, poliovirus, foot and mouth disease, enterovirus 71 infection, and poxvirus infection). The compounds are also useful in the prevention or treatment of protozoal infections (e.g., malaria and leishmaniasis) and fungal infections, such as in the treatment of these infections.

[0015] The present invention also provides a pharmaceutical composition comprising the compound of the present invention and a pharmaceutically acceptable carrier.

[0016] The present invention also provides compounds or pharmaceutical compositions of the present invention for use as pharmaceuticals.

[0017] The present invention also provides compounds or pharmaceutical compositions of the present invention for use in the prevention or treatment of diseases or disorders in which inhibition of N-myristoyltransferase results in a therapeutic or preventive effect.

[0018] The present invention also provides the use of the compounds of the present invention for the manufacture of pharmaceuticals for the prevention or treatment of diseases or disorders in which inhibition of N-myristoyltransferase results in a therapeutic or preventive effect.

[0019] The present invention also provides a method for treating or preventing a disease or disorder in which inhibition of N-myristoyltransferase results in a therapeutic or preventive effect in a mammal, wherein the mammal is given a therapeutically effective amount of the compound or pharmaceutical composition of the present invention.

[0020] The present invention also provides a kit of parts comprising: (a) a first pharmaceutical composition comprising the compound of the present invention and a pharmaceutically acceptable carrier; and (b) a second pharmaceutical composition comprising a further therapeutic agent, preferably a further N-myristoyltransferase inhibitor and a pharmaceutically acceptable carrier. [Brief explanation of the drawing]

[0021] (Brief explanation of the drawing) [Figure 1] Figure 1a shows the metabolic viability of P-493-6 cell lines treated with Example Compound 3 at the indicated concentrations for 72 hours, inducing various levels of c-MYC expression; Figure 1b shows the metabolic viability of P-493-6 cell lines treated with Example Compound 2 at the indicated concentrations for 72 hours, inducing various levels of c-MYC expression. [Figure 2]Figure 2a shows the metabolic viability of Shep-ER-MYCN cell lines treated with the indicated concentration of Example Compound 3 for 72 hours, with and without MYCN induction; Figure 2b shows the metabolic viability of Shep-ER-MYCN cell lines treated with the indicated concentration of Example Compound 2 for 72 hours, with and without MYCN induction. [Figure 3] Figure 3a shows the metabolic viability of SKNAS-ER-MYCN cell lines treated with the indicated concentration of Example Compound 3 for 92 hours, with and without MYCN induction; Figure 3b shows the metabolic viability of Shep-ER-MYCN cell lines treated with the indicated concentration of Example Compound 2 for 72 hours, with and without MYCN induction. [Figure 4] Figure 4 shows the therapeutic efficacy (percentage reduction in parasite load) of three different doses of Example Compound 3 of the present invention against Plasmodium falciparum in vivo up to 7 days post-infection, compared to standard treatment (chloroquine) and control mice (details of the mouse malaria model are provided in (g) of the "Details of Biological Assays and Results" section below). [Figure 5] Figure 5a shows the therapeutic efficacy (reduction in tumor size) of Example Compound 2 when administered orally to a subcutaneous xenograft DOHH-2 lymphoma model using 6-8 week old female CB17 / SCID mice, compared to the vehicle. Figure 5b shows the therapeutic efficacy (reduction in tumor size) of Example Compound 2 when administered intraperitoneally to a subcutaneous xenograft DOHH-2 lymphoma model using 6-8 week old female CB17 / SCID mice, compared to the vehicle. Figure 5c shows the therapeutic efficacy (reduction in tumor size) of Example 129 when administered intraperitoneally to a subcutaneous xenograft DOHH-2 lymphoma model using 6-8 week old female CB17 / SCID mice, compared to the vehicle. [Modes for carrying out the invention]

[0022] (Detailed description of the invention) The present invention provides compounds that are NMT inhibitors. As used herein, the term “NMT inhibitor” is intended to encompass any part that binds to NMT and inhibits its activity. Inhibitors can act as competitive inhibitors or partially competitive inhibitors. Inhibitors can bind to NMT (or inhibit NMT via another mechanism) via a myr-CoA binding pocket or a peptide binding pocket. The compounds of the present invention preferably bind to and inhibit NMT via a peptide binding pocket.

[0023] (definition) The following definitions apply to terms used throughout this Specification unless otherwise specified.

[0024] As used herein, the term "alkyl" means both straight-chain saturated hydrocarbon groups and branched-chain saturated hydrocarbon groups. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, i-butyl, sec-butyl, pentyl, and hexyl groups. Among unbranched alkyl groups, preferably, are methyl, ethyl, n-propyl, isopropyl, and n-butyl groups, e.g., methyl, ethyl, n-propyl, and n-butyl. Among branched alkyl groups, isopropyl, t-butyl, i-butyl, 1-ethylpropyl, and 1-ethylbutyl groups, e.g., t-butyl, i-butyl, 1-ethylpropyl, and 1-ethylbutyl groups may be mentioned.

[0025] As used herein, the term “alkoxy” (e.g., methoxy) means the O-alkyl (e.g., O-methyl) group, where “alkyl” is used as described above. Examples of alkoxy groups include methoxy and ethoxy groups. Other examples include propoxy and butoxy groups.

[0026] As used herein, the term "alkenyl" refers to both straight-chain and branched-chain unsaturated hydrocarbon groups having at least one carbon-carbon double bond. Examples of alkenyl groups include ethenyl, propenyl, butenyl, pentenyl, and hexenyl. Preferred alkenyl groups include ethenyl, 1-propenyl, 2-propenyl, and buta-2-enyl.

[0027] As used herein, the term "cycloalkyl" means a saturated group in a cyclic system. Cycloalkyl groups can be monocyclic or bicyclic. Bicyclic groups may be condensed or crosslinked, for example. Examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of bicyclic cycloalkyl groups include bicyclooctane, bicyclononane, bicyclodecane (decalin), and bicyclooctane. A further example of a cycloalkyl group is adamantane. Preferred examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Other examples of monocyclic cycloalkyl groups are cycloheptyl and cyclooctyl. An example of a bicyclic cycloalkyl group is bicyclo[2.2.1]hepta-2-yl. Preferably, the cycloalkyl group is monocyclic. Cycloalkyl groups, e.g., C 3-6 A cycloalkyl group consists of a single carbon atom, for example: [ka] via; or combined, for example: [ka] It may also be connected to the rest of the molecule via (where the dashed line indicates connection to the rest of the compound).

[0028] As used herein, the term "aryl" means a carbocyclic aromatic ring system, such as phenyl.

[0029] As used herein, the terms "halogen" or "halo" mean fluorine, chlorine, bromine, or iodine. Fluorine, chlorine, and bromine are preferred, and fluorine and chlorine are particularly preferred.

[0030] As used herein, the term “heterocyclyl (or heterocyclic)” means an aromatic or non-aromatic cyclic group of carbon atoms in which 1 to 4 carbon atoms are replaced by one or more heteroatoms independently selected from nitrogen (N), oxygen (O), or sulfur (S). A heterocyclyl (or heterocyclic) group may be monocyclic or bicyclic, for example. In a bicyclic heterocyclyl (or heterocyclic) group, one or more heteroatoms may be present in each ring, or in only one of the rings. The heteroatoms may be S, O, or N, preferably O or N.

[0031] Examples of monocyclic non-aromatic heterocyclyl (or heterocyclic) groups include azilidinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, tetrahydrofuranil, tetrahydropyranil, morpholinyl, thiomorpholinyl, azepanyl, and diazepanyl (e.g., 1,4-diazepanyl, 1,1-diazepanyl, or 1,5-diazepanyl, and preferably 1,4-diazepanyl).

[0032] Examples of bicyclic non-aromatic heterocyclyl (or heterocyclic) groups include diazabicycloheptanyl (e.g., 3,6-diazabicyclo[3.2.0]heptanyl), 1H-octahydropyrrolo[3,4-b]pyridinyl, 2,5-diazabicyclo[2.2.1]heptanyl, cis-octahydropyrrolo[3,4-b]pyridinyl, cis-octahydropyrrolo[3,4-c]pyridinyl, 3,7-diazabicyclo[3.3.1]nonanyl, 2,6-diazaspiro[3.3]heptanyl, and octahydropyrrolo[3,2-b]pyro Ryl, 1,7-diazaspiro[4.4]nonanyl, 1,8-diazaspiro[4.5]decanyl, decahydro-2,7-naphthilidinyl, 2,8-diazaspiro[5.5]undecanyl, 3,6-diazabicyclo[3.2.0]heptane, 2,8-diazaspiro[4.5]decanyl, octahydropyrrolo[3,4-c]pyrrolyl, trans-octahydro-1H-pyrrolo[3,4-b]pyridinyl, 2,6-diazaspiro[4.5]decanyl, 2,7-diazaspiro[4.5]decanyl, 1,7-diazaspiro[3.5]nonanyl 1,6-diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, (4aR,8aR)-decahydro-1,5-naphthilidinyl, 3,9-diazaspiro[5.5]undecanyl, (3aS,6aS)-octahydropyrrolo[2,3-c]pyrrolyl, 2,9-diazaspiro[6.6]tridecanyl, 3,8-diazabicyclo[4.2.0]octanyl, 3,7-diazabicyclo[4.2.0]octanyl, 9,9-dimethyl-3,7-diazabicyclo[3. 3.1] Nonanyl, cis-octahydropyrrolo[3,4-c]pyridinyl, cis-decahydro-1,7-naphthilidinyl, 2,7-diazabicyclo[4.2.0]octanyl, (4aS,7aS)-octahydropyrrolo[3,4-b][1,4]oxazinyl, 2,6-diazaspiro[3.4]octanyl, 1,9-diazaspiro[6.6]tridecanyl, (4aS,8aS)-decahydro-1,5-naphthilidinyl, trans-decahydro-1,7-naphthiridine, (1S,2S)-2,5-diazabicyclo[2.2.Examples include heptanyl, trans-decahydro-1,7-naphthilidinyl, rac-(4aR,8aR)-octahydro-2H-pyrido[4,3-b]morpholinyl, decahydro-1,6-naphthilidinyl, octahydro-1H-pyrrolo[3,2-c]pyridinyl, rac-(3aR,6aR)-octahydropyrrolo[2,3-c]pyrrolyl, and decahydropyrrolo[3,2-c]azepinyl.

[0033] Examples of monocyclic aromatic heterocyclyl (or heterocyclic) groups include furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyridyl, triazolyl, triazinyl, tetrazolyl, pyridazyl, isothiazolyl, isoxazolyl, pyrazinyl, pyrazolyl, and pyrimidinyl.

[0034] Examples of bicyclic aromatic heterocyclyl groups (or heterocycles) include quinoxalinyl, quinazolinyl, pyridopyradinyl, benzoxazolyl, benzothiophenyl, benzimidazolyl, naphthilidinyl, quinolinyl, benzofuranil, indolyl, benzothiazolyl, oxazolyl[4,5-b]pyridyl, pyridopyrimidinyl, isoquinolinyl, and benzodioxazolyl.

[0035] Further examples of bicyclic aromatic heterocyclyl groups include those in which one ring is aromatic and the other is non-aromatic, such as dihydrobenzofuranyl, indanyl, indolinyl, isoindolinyl, tetrahydroisoquinolinyl, tetrahydroquinolyl, and benzoazepanyl.

[0036] (The compound of the present invention) The present invention provides compounds of formula (I), or pharmaceutically acceptable esters, amides, or carbamates thereof, or salts comprising such esters, amides, or carbamates. The compounds of the present invention are NMT inhibitors.

[0037] In one embodiment, a compound of formula (I) or a pharmaceutically acceptable ester, amide, carbamate, or salt thereof is provided. In one embodiment, the compound of formula (I) is provided in the form of a pharmaceutically acceptable ester, amide, or carbamate salt thereof. In one embodiment, the pharmaceutically acceptable ester, amide, or carbamate of the compound of formula (I) is not a salt. In one embodiment, the compound of formula (I) is provided in the form of a pharmaceutically acceptable ester. In one embodiment, the compound of formula (I) is provided in the form of a pharmaceutically acceptable amide. In one embodiment, the compound of formula (I) is provided in the form of a pharmaceutically acceptable carbamate. In one embodiment, the compound of formula (I) is provided in the form of a pharmaceutically acceptable salt. In one embodiment, the compound of formula (I) is provided.

[0038] The inventors have discovered that the compound of formula (I) is an inhibitor of human NMT1 and HsNMT2. In particular, the data in this application show that the compound is an inhibitor of human NMT1 (HsNMT1) at extremely low micromolar or nanomolar concentrations. 50 The presence of this value indicates that it is a particularly potent human NMT1 inhibitor (it has been well established that HsNMT1 and HsNMT2 are usually inhibited to the same extent by NMT inhibitor compounds (PLoS Neglected Tropical Diseases 6(4): e1625)). The inventors also discovered that the compound of formula (I) is an inhibitor of Plasmodium vivax NMT.

[0039] To further test the efficacy of the compounds of the present invention, specific compounds of the present invention were tested in metabolic activity cell assays using eight different cancer cell lines. The compounds of the present invention inhibited metabolic activity in each of the metabolic activity assays and are therefore considered useful as agents for the prevention and / or treatment of cancer because they are inhibitors of human NMT1 and / or NMT2.

[0040] Plasmodium falciparum (Pf) NMT EC 50The values ​​for specific compounds of the present invention were measured by measuring the amount of parasitic DNA in human erythrocytes incubated with synchronized late-stage Plasmodium falciparum trophoblasts. The specific compounds of the present invention inhibited parasitic infection of cells in this assay. The compounds of the present invention were also shown to reduce the parasitic load of Plasmodium falciparum in mice transplanted with human erythrocytes. Therefore, the compounds of the present invention are considered useful as agents for the prevention and / or treatment of parasitic infections, such as malaria, because they are inhibitors of parasitic NMT, e.g., Pf NMT.

[0041] The compounds of the present invention are potent and combine this with good metabolic stability. The results of Examples (e) and (f) below show the rat hepatocyte half-life, rat IV half-life, and rat oral bioavailability of various example compounds of the present invention.

[0042] The combination of the above-described properties makes the compounds of the present invention particularly suitable for use as pharmaceuticals, especially for oral administration.

[0043] The compounds of the present invention may contain a chiral center, or the molecule as a whole may be chiral. Individual stereoisomers (enantiomers and diastereoisomers) and mixtures thereof are within the scope of the present invention.

[0044] To avoid misunderstanding, further embodiments may be created by combining any one feature of the compound of the present invention, or a more preferred or most preferred embodiment, with any other feature of the compound of the present invention, or a more preferred or most preferred embodiment.

[0045] The limitations described herein for compounds of formula (I) apply equally to compounds of formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Im), (In), (Io), (Ip), and (Iq).

[0046] Where a substituent is indicated as optionally substituted in formula (I) in the embodiments and preferences described below, the substituent may be bonded to an available carbon atom (i.e., a carbon atom bonded to a hydrogen atom, i.e., a CH group), or it may be bonded to an available nitrogen atom (i.e., a nitrogen atom bonded to a hydrogen atom, i.e., an NH group). The substituent replaces a hydrogen atom bonded to a carbon atom or a hydrogen atom bonded to a nitrogen atom.

[0047] Preferably, in one embodiment, the related group is substituted. In another embodiment, the related group is unsubstituted.

[0048] In the compound of formula (I), n1 is 1 or 2, and n2 is 1 or 2. In one preferred embodiment, n1 is 1, and n2 is 1 or 2. In a particularly preferred embodiment, n1 is 1, and n2 is 1. In such an embodiment, the compound of formula (I) is the compound of formula (Ia): [ka] .

[0049] In the compound of formula (I), X 1 CR x Selected from the group consisting of and N. Preferably, X 1 is N. In such an embodiment, the compound of formula (I) is the compound of formula (Ib): [ka] .

[0050] In the compound of formula (I), if present, R x -C is a hydrogen atom, a halogen atom, and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 A selection may be made from the group consisting of alkyl groups. Preferably, R x-C optionally substituted with hydrogen, halogen (preferably F or Cl), halogen (preferably F or Cl), -OCH3, or -OCF3. 1-4 Selected from the group consisting of alkyl groups. More preferably, R x These are hydrogen, F, Cl, and -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R x It is hydrogen.

[0051] In the compound of formula (I), R 1 -C is a hydrogen atom; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 Alkyl; and -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -CH3, -OCH3, and -OCF3. 3-6 They may be selected from the group consisting of cycloalkyl groups; R 2 -C is a hydrogen atom; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 Alkyl; and -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -CH3, -OCH3, and -OCF3. 3-6 They may be selected from the group consisting of cycloalkyls; or R 1 and R 2 These include a C atom, along with the atom to which they are bonded, which contains one heteroatom selected from the group consisting of O and N. 3-6 They may be linked to form a cycloalkyl group or a 3-6 member non-aromatic heterocyclyl group, where the C 3-6 The cycloalkyl group or the 3- to 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens, -OH, -CH3, -OCH3, and -OCF3.

[0052] One preferred embodiment, R 1 -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 1 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 1 is hydrogen and -C 1-3 Selected from the group consisting of alkyl groups. More preferably, R 1 R is selected from the group consisting of hydrogen and methyl. More preferably, 1 It is methyl.

[0053] One preferred embodiment, R 2 -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 2 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 2 is hydrogen and -C 1-3 Selected from the group consisting of alkyl groups. More preferably, R 2 R is selected from the group consisting of hydrogen and methyl. More preferably, 2 It is methyl.

[0054] One preferred embodiment, R 1 and R 2 -C is a hydrogen atom, and each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 Selected from the group consisting of alkyl groups (for example, R 1-C 1-4 It is alkyl and R 2 -C 1-4 Is it alkyl; or R 1 -C 1-4 It is alkyl and R 2 Is it hydrogen; or R 1 is hydrogen, and R 2 (is hydrogen). More preferably, R 1 and R 2 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups (for example, R 1 is -C 1-4 It is alkyl and R 2 is -C 1-4 Is it alkyl; or R 1 is -C 1-4 It is alkyl and R 2 Is it hydrogen; or R 1 is hydrogen, and R 2 (is hydrogen). More preferably, R 1 and R 2 is hydrogen and -C 1-3 Selected from the group consisting of alkyl groups (for example, R 1 is -C 1-3 It is alkyl and R 2 is -C 1-3 Is it alkyl; or R 1 is -C 1-3 It is alkyl and R 2 Is it hydrogen; or R 1 is hydrogen, and R 2 (is hydrogen). More preferably, R 1 and R 2 R is selected from the group consisting of hydrogen and methyl (for example, R1 is methyl and R 2 Is it methyl; or R 1 is methyl and R 2 Is it hydrogen; or R 1 It has hydrogen and R 2 (It is hydrogen).

[0055] One preferred embodiment, R 1 -C 1-4 It is alkyl; and R 2 -C 1-4 It is alkyl. More preferably, R 1 is -C 1-4 It is alkyl; and R 2 is -C 1-4 It is alkyl. More preferably, R 1 is -C 1-3 It is alkyl; and R 2 is -C 1-3 It is alkyl. More preferably, R 1 is methyl; and R 2 It is methyl.

[0056] In another preferred embodiment, R 1 -C 1-4 It is alkyl; and R 2 is hydrogen. More preferably, R 1 is -C 1-4 It is alkyl; and R 2 is hydrogen. More preferably, R 1 is -C 1-3 It is alkyl; and R 2 is hydrogen. More preferably, R 1 is methyl; and R 2It is hydrogen.

[0057] In one preferred embodiment, R 1 is hydrogen, and R 2 It is hydrogen.

[0058] In another embodiment, R 1 and R 2 These include a C atom, along with the atom to which they are bonded, which contains one heteroatom selected from the group consisting of O and N. 3-6 The C may be linked to form a cycloalkyl group (i.e., a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group) or a 3- to 6-membered non-aromatic heterocyclyl group (i.e., a 3, 4, 5, or 6-membered non-aromatic heterocyclyl group), where the C 3-6 The cycloalkyl group or the 3-6 member non-aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens, -OH, -CH3, -OCH3, and -OCF3. For example, R 1 and R 2 They are linked together with the atom to which they are bonded to form a C3-5 cycloalkyl group (i.e., a cyclopropyl group, a cyclobutyl group, or a cyclopentyl group) or a 3- to 5-membered non-aromatic heterocyclyl group (i.e., a 3, 4, or 5-membered non-aromatic heterocyclyl group) containing one heteroatom selected from the group consisting of O and N, where the C3-5 cycloalkyl group or the 3- to 5-membered non-aromatic heterocyclyl group is optionally substituted with one or two substituents, each independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. Also, for example, R 1 and R 2 They are linked together with the atoms to which they are bonded, so as to form a C3-5 cycloalkyl group, where each C3-5 cycloalkyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. Also, for example, R 1 and R2 They are linked together with the atoms to which they are bonded, so as to form a C3-5 cycloalkyl group, where the C3-5 cycloalkyl group is optionally substituted with one substituent selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. Also, for example, R 1 and R 2 They are linked together with the atoms to which they are bonded, so that they form a C3-5 cycloalkyl group.

[0059] In another embodiment, R 1 and R 2 They are, together with the atoms to which they are bonded, and they are C 3-6 The C is linked to form a cycloalkyl group (i.e., a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group), where the C 3-6 The cycloalkyl group is optionally substituted with one substituent selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. For example, R 1 and R 2 They are, together with the atoms to which they are bonded, and they are C 3-6 They are linked to form a cycloalkyl group (i.e., a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group).

[0060] To avoid misunderstanding, R 1 and R 2 In an embodiment where they are linked, R 1 and R 3 They are not connected.

[0061] R 3 -C is a hydrogen atom; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4Alkyl; and -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -CH3, -OCH3, and -OCF3. 3-6- A selection may be made from the group consisting of cycloalkyl groups. Preferably, R 3 -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 3 -C is optionally substituted with hydrogen and 1, 2, or 3 F atoms. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 3 -C is optionally substituted with hydrogen and 1, 2, or 3 F atoms. 1-3 Selected from the group consisting of alkyl groups. More preferably, R 3 R is selected from the group consisting of hydrogen and methyl atoms optionally substituted with 1, 2, or 3 F atoms. For example, R 3 Is it hydrogen; or R 3 Is it methyl; or R 3 It is -CF3.

[0062] In another embodiment, R 1 and R 3 They may be linked together with the atom to which they are bonded so as to form a 3- to 6-membered non-aromatic heterocyclyl group (i.e., a 3, 4, 5, or 6-membered non-aromatic heterocyclyl group) containing one N heteroatom, where the 3- to 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3, e.g., halogens, -OH, -OCH3, and -OCF3. For example, R 1 and R 3They are linked together with the atom to which they are bonded so that they form a 4- to 6-membered non-aromatic heterocyclyl group (i.e., a 4, 5, or 6-membered non-aromatic heterocyclyl group) containing one N heteroatom, where the 4- to 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3, for example, halogens, -OH, -OCH3, and -OCF3. 1 and R 3 They are linked together with the atom to which they are bonded, so that they form a 5 or 6-membered non-aromatic heterocyclyl group containing one N heteroatom, where the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3, for example, halogens, -OH, -OCH3, and -OCF3. Also, for example, R 1 and R 3 They are linked together with the atom to which they are bonded so that they form a 5 or 6-membered non-aromatic heterocyclyl group containing one N heteroatom, where the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one substituent selected from the group consisting of halogen, -CH3, -OH, -OCH3, and -OCF3, for example, halogen, -OH, -OCH3, and -OCF3. Also, for example, R 1 and R 3 They are linked together with the atom to which they are bonded, so that they form a 5 or 6-membered non-aromatic heterocycline group containing one N heteroatom.

[0063] In another embodiment, R 1 and R 3They are linked together with the atom to which they are bonded so that they form a 4 or 5-membered non-aromatic heterocyclyl group containing one N heteroatom, where the 4 or 5-membered non-aromatic heterocyclyl group is optionally substituted with one substituent selected from the group consisting of halogen, -CH3, -OH, -OCH3, and -OCF3, for example, halogen, -OH, -OCH3, and -OCF3. For example, R 1 and R 3 They are linked together with the atom to which they are bonded, so that they form a 4 or 5-membered non-aromatic heterocycline group containing one N heteroatom.

[0064] To avoid misunderstanding, R 1 and R 3 In an embodiment where they are linked, R 1 and R 2 They are not connected.

[0065] In the compound of formula (I), X 2 CR 4 Selected from the group consisting of and N. Preferably, X 2 CR 4 In such an embodiment, the compound of formula (I) is the compound of formula (Ic): [ka] .

[0066] If present, R 4 These are hydrogen; halogens; and each substituent is a halogen, -OH, -OCH3, -OCF3, and -NR. a R b -C which is optionally substituted with one, two, or three substituents independently selected from the group consisting of 1-4 A selection may be made from the group consisting of alkyl groups. Preferably, R 4 -C is a molecule in which hydrogen, halogens, and -C molecules are optionally substituted with one, two, or three substituents, each independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4Selected from the group consisting of alkyl groups. More preferably, R 4 -C is optionally substituted with hydrogen; halogen; and one substituent selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 4 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups. In one particularly preferred embodiment, R 4 R is selected from the group consisting of hydrogen and methyl, for example, 4 It is hydrogen.

[0067] Alternatively, R 4 -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 4 R is selected from the group consisting of hydrogen and methyl atoms optionally substituted with 1, 2, or 3 F atoms, for example, 4 Is it hydrogen; or R 4 Is it methyl; or R 4 It is -CF3.

[0068] If present, each R a and R b is hydrogen and -C 1-4 They may be independently selected from the group consisting of alkyl groups. Preferably, each R a and R b R may be independently selected from the group consisting of hydrogen and methyl. For example, R a is hydrogen, and R b Is it hydrogen; or R a is methyl and R b Is it hydrogen; or R a is methyl and R b It is methyl.

[0069] A preferred embodiment of the present invention, R 3 and R 4Each of them is hydrogen.

[0070] In the compound of formula (I), R 5a and R 5d This is selected from the group consisting of hydrogen; halogens; methyl molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and methoxy molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. Preferably, R 5a and R 5d is selected from the group consisting of hydrogen; F; Cl; methyl optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and methoxy optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. More preferably, R 5a and R 5d is selected from the group consisting of hydrogen; F; Cl; methyl and methoxy. More preferably, R 5a and R 5d R is selected from the group consisting of hydrogen and methyl. In one very preferred embodiment, R 5a and R 5d Each of them is hydrogen.

[0071] One preferred embodiment, R 5a is hydrogen, and R 5d This is selected from the group consisting of hydrogen; halogens; methyl molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and methoxy molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. Preferably, R 5a is hydrogen, and R 5dis selected from the group consisting of hydrogen; F; Cl; methyl optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and methoxy optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. More preferably, R 5a is hydrogen, and R 5d is selected from the group consisting of hydrogen; F; Cl; methyl and methoxy. More preferably, R 5a is hydrogen, and R 5d This is independently selected from the group consisting of hydrogen and methyl.

[0072] One preferred embodiment, R 5d is hydrogen, and R 5a This is selected from the group consisting of hydrogen; halogens; methyl molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and methoxy molecules, each of which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. More preferably, R 5d is hydrogen, and R 5a This is selected from the group consisting of hydrogen; F; Cl; methyl optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and methoxy optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. More preferably, R 5d is hydrogen, and R 5a is selected from the group consisting of hydrogen; F; Cl; methyl and methoxy. More preferably, R 5d is hydrogen, and R 5a This is independently selected from the group consisting of hydrogen and methyl.

[0073] In the compound of formula (I), R 5b and R 5c-C is a hydrogen atom; a halogen atom; and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 They may be independently selected from the group consisting of cycloalkyl groups; Or R 5b and R 5c They may be linked together with the atom to which they are bonded to form a six-membered aryl group or a five- or six-membered aromatic heterocyclyl group containing one or two heteroatoms selected from the group consisting of S, O, and N, wherein the six-membered aryl group or the five- or six-membered aromatic heterocyclyl group is optionally substituted with one or two substituents, each independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3.

[0074] One preferred embodiment, R 5b and R 5c -C is a hydrogen atom; a halogen atom; and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OCH3, -OH, -OCH3, and -OCF3, for example, halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups. More preferably, R5b and R 5c -C is optionally substituted with one substituent selected from the group consisting of hydrogen; halogen; halogen, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and -OC optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and C optionally substituted with one substituent selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups.

[0075] More preferably, R 5b and R 5c -C is optionally substituted with hydrogen; halogen; and one substituent selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 5b and R 5c These are hydrogen; F; Cl; and -C 1-4 Selected from the group consisting of alkyl, for example, R 5b and R 5c Each of them is hydrogen, independently of the others.

[0076] In one particularly preferred embodiment, R 5a and R 5d is hydrogen, and R 5b and R 5c -C 1-4 Selected from the group consisting of alkyl groups. For example, R 5a and R 5d is hydrogen, and R 5b and R 5c -C is optionally substituted with hydrogen, halogen, and one substituent selected from the group consisting of halogen, -OH, -OCH3, and -OCF3 groups. 1-4 Selected from the group consisting of alkyl groups.

[0077] One preferred embodiment, R 5b is hydrogen, and R 5c -C is a hydrogen atom; a halogen atom; and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups. More preferably, R 5b is hydrogen, and R 5c -C is optionally substituted with one substituent selected from the group consisting of hydrogen; halogen; halogen, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and -OC optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and C optionally substituted with one substituent selected from the group consisting of halogens, -OH, -CH3, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups. More preferably, R 5b is hydrogen, and R 5c -C is optionally substituted with hydrogen; halogen; and one substituent selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 5b is hydrogen, and R 5c These are hydrogen; F; Cl; and -C 1-4 Selected from the group consisting of alkyl (e.g., hydrogen; F; Cl; and methyl). In such embodiments, preferably R 5a and R 5dEach of them is hydrogen.

[0078] In one particularly preferred embodiment, R 5c is hydrogen, and R 5c R is selected from the group consisting of hydrogen; F; and Cl. In such embodiments, preferably R 5a and R 5d Each of them is hydrogen.

[0079] In one particularly preferred embodiment, R 5c is hydrogen, and R 5b R is selected from the group consisting of hydrogen; F; and Cl. In such embodiments, preferably R 5a and R 5d Each of them is hydrogen.

[0080] One preferred embodiment, R 5c is hydrogen, and R 5b -C is a hydrogen atom; a halogen atom; and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups. More preferably, R 5c is hydrogen, and R 5b -C is optionally substituted with one substituent selected from the group consisting of hydrogen; halogen; halogen, -OH, -OCH3, and -OCF3. 1-4 Alkyl; and -OC optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4Alkyl; and C optionally substituted with one substituent selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups. More preferably, R 5c is hydrogen, and R 5b -C is optionally substituted with hydrogen; halogen; and one substituent selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 5c is hydrogen, and R 5b These are hydrogen; F; Cl; and -C 1-4 Selected from the group consisting of alkyl (e.g., hydrogen; F; Cl; and methyl). In such embodiments, preferably R 5a and R 5d Each of them is hydrogen.

[0081] In one particularly preferred embodiment, R 5b is hydrogen, and R 5c is hydrogen and C 1-4 Selected from the group consisting of alkyl (e.g., hydrogen and methyl). In such embodiments, preferably R 5a and R 5d Each of these is hydrogen. In one particularly preferred embodiment, R 5a , R 5b , R 5c , and R 5d Each of them is hydrogen.

[0082] In another embodiment, R 5b and R 5c They are linked together with the atom to which they are bonded so as to form a six-membered aryl group or a five- or six-membered aromatic heterocyclyl group containing one or two heteroatoms selected from the group consisting of S, O, and N, where the six-membered aryl group or the five- or six-membered aromatic heterocyclyl group is optionally substituted with one or two substituents, each substituent independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. For example, R 5band R 5c They are linked together with the atom to which they are bonded so as to form a 6-membered aryl group or a 5 or 6-membered aromatic heterocyclyl group containing one or two heteroatoms selected from the group consisting of O and N, where the 6-membered aryl group or the 5 or 6-membered aromatic heterocyclyl group is optionally substituted with one or two substituents, each independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. Also, for example, R 5b and R 5c They are linked together with the atom to which they are bonded so that they form a six-membered aryl group or a five- or six-membered aromatic heterocyclyl group containing one or two N heteroatoms, where the six-membered aryl group or the five- or six-membered aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. For example, R 5b and R 5c They are linked together with the atom to which they are bonded so that they form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two N heteroatoms. In such embodiments, R 5a and R 5d These could each be, for example, hydrogen.

[0083] In the compound of formula (I), R 6 R may be selected from the group consisting of hydrogen and methyl. Preferably, 6 It is hydrogen.

[0084] A preferred embodiment of the present invention, R 3 , R 4 , and R 6 Each of them is hydrogen.

[0085] In the compound of formula (I), p is 0, 1, or 2. For example, p may be 0 or 1. In one preferred embodiment, p is 0.

[0086] A preferred embodiment of the present invention, R 6 is hydrogen; and p is 0. In another preferred embodiment of the present invention, R 3 , R 4 , and R 6 Each of them is a hydrogen atom; and p is 0.

[0087] In the compound of formula (I), if present, each R 7 -C 1-4 It may be alkyl. Preferably, if present, each R 7 -C is independently and optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 It is alkyl. More preferably, if present, each R 7 Independently, -C 1-4 It is alkyl. In another preferred embodiment, if present, each R 7 This may be a methyl molecule optionally substituted with one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3.

[0088] In the compound of formula (I), R 8 This refers to hydrogen; halogen; -OH; -CN; and -C, which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkyl; -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 3-6 Cycloalkyl; -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4Alkenyl (for example, -C) 2-4 Alkenyls; and -OCs, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 A selection may be made from the group consisting of alkyl groups. Preferably, R 8 This is hydrogen; halogen; and -C, which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkyl; -C, optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, -CH3, -OH, -CN, and methoxy molecules, each substituent optionally substituted with a halogen, -CH3, -OH, -CN, and one, two, or three halogens (e.g., one, two, or three F atoms). 3-4 Cycloalkyl; -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkenyl (for example, -C) 2-4 Alkenyls; and -OCs, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 8 -C, which is a hydrogen atom; a halogen (e.g., F or Cl); and a methoxy molecule whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4Selected from the group consisting of alkyl groups. More preferably, R 8 -C optionally substituted with one substituent selected from the group consisting of hydrogen; halogen (e.g., F or Cl); halogen, -OH, -CN, and methoxy optionally substituted with 1, 2, or 3 halogens. 1-4 Alkyl; and -OC optionally substituted with one substituent selected from the group consisting of halogens, -OH, CN, and methoxy optionally substituted with 1, 2, or 3 halogens. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 8 -C optionally substituted with one substituent selected from the group consisting of hydrogen; halogen (e.g., F or Cl); halogen and methoxy optionally substituted with 1, 2, or 3 halogens. 1-4 Alkyl; and optionally substituted with one substituent selected from the group consisting of halogens and methoxy molecules optionally substituted with one, two, or three halogens -OC 1-4 Selected from the group consisting of alkyl groups. More preferably, R 8 is hydrogen; halogen; -C 1-4 alkyl; and -OC 1-4 Selected from the group consisting of alkyl groups. For example, R 8 This is selected from the group consisting of hydrogen, halogens, methyl, and methoxy.

[0089] Alternatively, R 8 This is selected from the group consisting of hydrogen; halogens (e.g., F or Cl); methyl molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens; and methoxy molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, CN, and methoxy molecules optionally substituted with one, two, or three halogens. Preferably, R 8This is selected from the group consisting of hydrogen; halogens (e.g., F or Cl); methyl optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy optionally substituted with halogens and one, two, or three halogens; and methoxy optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy optionally substituted with halogens and one, two, or three halogens. More preferably, R 8 is selected from the group consisting of hydrogen; halogens (e.g., F or Cl); methyl optionally substituted with 1, 2, or 3 F atoms; and methoxy optionally substituted with 1, 2, or 3 F atoms. For example, R 8 is selected from the group consisting of hydrogen; halogen; methyl; -CF3; methoxy; and -OCF3. Preferably, R 8 is CF3. Preferably, R 8 It is Cl.

[0090] In another embodiment, R 8 -C 1-3 Alkyl; -C, optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, -OH, -CH3, -CN, and methoxy molecules, each substituent optionally substituted with a halogen (e.g., F), -OH, -CH3, -CN, and 1, 2, or 3 halogens (e.g., 1, 2, or 3 F atoms). 3-4 Cycloalkyl; and -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy molecules whose substituents are optionally substituted with halogens (e.g., F), -OH, -CN, and 1, 2, or 3 halogens (e.g., 1, 2, or 3 F atoms). 1-3 Selected from the group consisting of alkyl groups. In such embodiments, preferably R 9It is hydrogen.

[0091] In the compound of formula (I), R 9 -C is a hydrogen atom and a C atom whose substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 A selection may be made from the group consisting of alkyl groups. Preferably, R 9 -C is optionally substituted with hydrogen and one substituent selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-4 Selected from the group consisting of alkyl groups. More preferably, R 9 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 9 R is selected from the group consisting of hydrogen and methyl. In one particularly preferred embodiment, 9 It is hydrogen.

[0092] Alternatively, R 9 R is selected from the group consisting of hydrogen and methyl molecules, each optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. Preferably, 9 R is selected from the group consisting of hydrogen and methyl atoms optionally substituted with 1, 2, or 3 F atoms. For example, R 9 Is it hydrogen; or R 9 Is it methyl; or R 9 It is -CF3.

[0093] A preferred embodiment of the present invention, R 6 and R 9 Each of them is hydrogen; and p is 0. In another preferred embodiment of the present invention, R 3 , R 4 , R 6 , and R 9 Each of them is hydrogen; and p is 0.

[0094] In the compound of formula (I), R8 and R 9 These are six-membered aryl groups containing one or two heteroatoms (e.g., one heteroatom) selected from N, O, and S, along with the atom to which they are bonded, C 5-6 They may be linked to form a cycloalkyl group or a 5 or 6-membered aromatic heterocyclyl group, where the 6-membered aryl group, C 5-6 The cycloalkyl group or 5-6 member aromatic heterocyclyl group may be a halogen; -OH; -CN; or a -C group, each substituent may be a halogen, -OH, or a methoxy group optionally substituted with one, two, or three halogens, independently selected from the group consisting of halogens, -OH, and methoxy groups optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups.

[0095] In the compound of formula (I), R 8 and R 9 These are six-membered aryl groups containing one or two heteroatoms (e.g., one heteroatom) selected from N, O, and S, along with the atom to which they are bonded, C 5-6 They are linked to form a cycloalkyl group or a 5 or 6-membered aromatic heterocyclyl group, where the 6-membered aryl group, C 5-6 A cycloalkyl group or a 5 or 6-membered aromatic heterocyclyl group may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3, or -C 1-3 Alkyl; and -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogen, -OH, -OCH3, and -OCF3. 1-3It is optionally substituted with one, two, or three substituents (e.g., one substituent) independently selected from the group consisting of alkyl groups.

[0096] In one preferred embodiment, R 8 and R 9 They are, together with the atoms to which they are bonded, and they are C 5-6 They are linked to form a cycloalkyl group, where the C 5-6 Cycloalkyl groups are those in which each substituent is a halogen; -OH; -CN; and -C, which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents (e.g., one substituent) independently selected from the group consisting of alkyl groups.

[0097] In one preferred embodiment, R 8 and R 9 They are, together with the atoms to which they are bonded, and they are C 5-6 They are linked to form a cycloalkyl group, where the C 5-6 Cycloalkyl groups include halogens; -OH; -CN; and -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3. 1-3 Alkyl; and -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogen, -OH, -OCH3, and -OCF3. 1-3 It is optionally substituted with one, two, or three substituents (for example, one substituent) selected from the group consisting of alkyl groups.

[0098] More preferably, R 8 and R 9 They are linked together with the atom to which they are bonded so that they form a C5 cycloalkyl group, where each substituent is a halogen; -OH; -CN; and each substituent is a methoxy group optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, and methoxy groups optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents (e.g., one substituent) independently selected from the group consisting of alkyl groups.

[0099] More preferably, R 8 and R 9 They are linked together with the atom to which they are bonded, so as to form a C5 cycloalkyl group, where the C5 cycloalkyl group is a halogen; -OH; -CN; and each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. 1-3 Alkyl; and -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogen, -OH, -OCH3, and -OCF3. 1-3 It is optionally substituted with one, two, or three substituents (for example, one substituent) selected from the group consisting of alkyl groups.

[0100] Alternatively, R 8 and R 9They may be linked together with the atom to which they are bonded so as to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group comprising one or two heteroatoms selected from N, O, and S, wherein the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen; -OH; -CN; and -C, which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, and methoxy optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. For example, R 8 and R 9 They may be linked together with the atom to which they are bonded so as to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms selected from N and O, wherein the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one, two or three substituents independently selected from the group consisting of halogen; -OH; -CN; and methoxy optionally substituted with one, two or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. For example, R 8 and R 9They may be linked together with the atom to which they are bonded so as to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms selected from N and O, wherein the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one, two or three substituents independently selected from the group consisting of halogens (e.g., F or Cl); and methoxysulfites optionally substituted with one, two or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups.

[0101] In another embodiment, R 8 and R 9 They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, wherein the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one substituent selected from the group consisting of halogens (e.g., F or Cl); halogens and methoxy optionally substituted with one, two, or three halogens -C 1-4 Alkyl; and optionally substituted with one substituent selected from the group consisting of halogens and methoxy molecules optionally substituted with one, two, or three halogens -OC 1-4 It is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. For example, R 8 and R 9They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, wherein the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one substituent selected from the group consisting of halogens (e.g., F or Cl); halogens and methoxy optionally substituted with one, two, or three halogens -C 1-4 Alkyl; and optionally substituted with one substituent selected from the group consisting of halogens and methoxy molecules optionally substituted with one, two, or three halogens -OC 1-4 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups. For example, R 8 and R 9 They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, where the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group has a halogen substituent; -C 1-4 alkyl; and -OC 1-4 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups. Also, for example, R 8 and R 9 They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, where the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one or two substituents, each independently selected from the group consisting of hydrogen; halogen; methyl; and methoxy. In further embodiments, R 8 and R 9They may be linked together with the atom to which they are bonded to form a six-membered aryl group or a five- or six-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O.

[0102] Alternatively, in one embodiment, R 8 and R 9 They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, wherein each substituent is a halogen (e.g., F or Cl); each substituent is optionally substituted with a methoxy molecule optionally substituted with a halogen, -OH, -CN, and one, two, or three halogens, e.g., a methyl molecule optionally substituted with one, two, or three substituents independently selected from the group consisting of a halogen, -OH, and one, two, or three halogens; and each substituent is optionally substituted with a methoxy molecule optionally substituted with one, two, or three substituents independently selected from the group consisting of a halogen, -OH, CN, and one, two, or three halogens, e.g., a methoxy molecule optionally substituted with one or two substituents independently selected from the group consisting of a halogen, -OH, and one, two, or three halogens. For example, R 8 and R 9They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, where the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens (e.g., F or Cl); methyl, optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and methoxy optionally substituted with one, two, or three halogens; and one or two substituents independently selected from the group consisting of methoxy, optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and methoxy optionally substituted with one, two, or three halogens. Also, for example, R 8 and R 9 They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, where the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogens (e.g., F or Cl); methyl optionally substituted with one, two, or three F atoms; and methoxy optionally substituted with one, two, or three F atoms. Also, for example, R 8 and R 9 They may be linked together with the atom to which they are bonded to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N and O, where the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with one or two substituents independently selected from the group consisting of halogen; methyl; -CF3; methoxy; and -OCF3.

[0103] Alternatively, in one embodiment, R 8 and R9 They are linked together with the atom to which they are bonded to form a 5 or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N, O, and S, wherein the 5 or 6-membered aromatic heterocyclyl group is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen; -OH; -CN; and -C, where each substituent is optionally substituted with halogen, -OH, and methoxy optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 It is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups.

[0104] Alternatively, in one embodiment, R 8 and R 9 They are linked together with the atom to which they are bonded to form a 5 or 6-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N, O, and S, wherein the 5 or 6-membered aromatic heterocyclyl group is optionally substituted with halogen; -OH; -CN; and each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. 1-3 Alkyl; and -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogen, -OH, -OCH3, and -OCF3. 1-3 It is optionally substituted with one substituent selected from the group consisting of alkyl groups.

[0105] In one preferred embodiment, R 8 and R 9They are linked together with the atom to which they are bonded to form a five-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N, O, and S, wherein the five-membered aromatic heterocyclyl group is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen; -OH; -CN; and -C, which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, and methoxy optionally substituted with one, two, or three halogens. 1-4 Alkyl; and -OC molecules, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Independently selected from the group consisting of alkyl groups; optionally substituted with one, two, or three substituents.

[0106] In one preferred embodiment, R 8 and R 9 They are linked together with the atom to which they are bonded to form a five-membered aromatic heterocyclyl group containing one or two heteroatoms (e.g., one heteroatom) selected from N, O, and S, where the five-membered aromatic heterocyclyl group is a halogen; -OH; -CN; and each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -OCH3, and -OCF3. 1-3 Alkyl; and -OC, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogen, -OH, -OCH3, and -OCF3. 1-3 It is optionally substituted with one substituent selected from the group consisting of alkyl groups.

[0107] In one preferred embodiment, R 8 and R 9 They, along with the atoms to which they are bonded, [ka] They are linked to form a 5-membered aromatic heterocyclyl group selected from the group consisting of:. In one preferred embodiment, the 5-membered heterocyclyl group is [ka] Selected from the group consisting of:. In one preferred embodiment, the 5-membered heterocyclyl group is [ka] : In one preferred embodiment, the 5-membered heterocyclyl group is [ka] : In one preferred embodiment, the 5-membered heterocyclyl group is [ka] : In one preferred embodiment, the 5-membered heterocyclyl group is [ka] : is.

[0108] To avoid misunderstanding, in such an embodiment, [ka] represents a connection point, where, for example, [ka] teeth, [ka] It is equivalent to this.

[0109] In the compound of formula (I), Z may be a 5-13 member non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and where the 5-13 member non-aromatic heterocyclyl group is optionally substituted with halogens; each substituent is optionally substituted with halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; NR c R d ; and -OCs in which each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 They are optionally substituted with one, two, three, or four substituents independently selected from the group consisting of cycloalkyls (e.g., one, two, or three substituents; or one or two substituents; or one substituent); or when two substituents are in adjacent ring positions, they, together with the atom to which they are bonded, contain one heteroatom selected from the group consisting of O and N. 3-6 They may be linked to form a cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group, where the C 3-6 Cycloalkyl groups or 4- to 6-membered non-aromatic heterocyclyl groups (i.e., 4, 5, or 6-membered non-aromatic heterocyclyl groups) are defined as follows: each substituent is a halogen; each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups; R c and R d -C is a hydrogen atom; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-6 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Independently selected from the group consisting of cycloalkyls; Alternatively, Z is -NR 10 R 11 That is the case.

[0110] In the compound of formula (I), Z may be a 5-13 member non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and where the 5-13 member non-aromatic heterocyclyl group is optionally substituted with halogens; each substituent is optionally substituted with halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one, two, three, or four substituents independently selected from the group consisting of alkyl groups (e.g., one, two, or three substituents; or one or two substituents; or one substituent); Alternatively, Z is -NR 10 R 11 That is the case.

[0111] Alternatively, Z may be a 5-13 member non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and where each substituent of the 5-13 member non-aromatic heterocyclyl group is NR c R d ; and -OCs in which each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 They are optionally substituted with one, two, three, or four substituents independently selected from the group consisting of cycloalkyls (e.g., one, two, or three substituents; or one or two substituents; or one substituent); or when two substituents are in adjacent ring positions, they, together with the atom to which they are bonded, contain one heteroatom selected from the group consisting of O and N. 3-6 They may be linked to form a cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group, where the C 3-6 Cycloalkyl groups or 4-6 member non-aromatic heterocyclyl groups are each substituted with a halogen; each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups; R c and R d-C is a hydrogen atom; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-6 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Independently selected from the group consisting of cycloalkyls; Alternatively, Z is -NR 10 R 11 That is the case.

[0112] Alternatively, Z may be a 5-10 member non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and where the 5-10 member non-aromatic heterocyclyl group is optionally substituted with halogens; each substituent is optionally substituted with halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one, two, three, or four substituents independently selected from the group consisting of alkyl; (for example, one, two, or three substituents; or one or two substituents; or one substituent) Alternatively, Z is -NR 10 R 11 That is the case.

[0113] In this embodiment, where Z is a 5- to 13-membered non-aromatic heterocyclyl group (i.e., a 5, 6, 7, 8, 9, 10, 11, 12, or 13-membered non-aromatic heterocyclyl group), preferably the N heteroatom is X 1 It is directly bonded to the 6-membered aromatic heterocycline group of formula (I) which includes [the specified element].

[0114] In embodiments where Z is a 5-13 member non-aromatic heterocyclyl group, Z is azilidinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, tetrahydrofuranil, tetrahydropyranil, morpholinyl, thiomorpholinyl, azepanyl, diazepanyl (e.g., 1,4-diazepanyl, 1,1-diazepanyl, or 1,5-diazepanyl, and preferably 1,4-diazepanyl), diazabicycloheptanyl (e.g., 3,6-diazabicyclo[3.2.0]heptanyl), 1H-Octahydropyrrolo[3,4-b]pyridinyl, 2,5-diazabicyclo[2.2.1]heptanyl, cis-Octahydropyrrolo[3,4-b]pyridinyl, cis-Octahydropyrrolo[3,4-c]pyridinyl, 3,7-Diazabicyclo[3.3.1]nonanyl, 2,6-Diazaspiro[3.3]heptanyl, Octahydropyrrolo[3,2-b]pyrrolyl, 1,7-Diazaspiro[4.4]nonanyl, 1,8-Diazaspiro[4.5]decanyl, Decahydro-2,7-Naphthilidinyl, 2,8-Diazaspiro[5 .5]undecanyl, 3,6-diazabicyclo[3.2.0]heptane, 2,8-diazaspiro[4.5]decanyl, octahydropyrrolo[3,4-c]pyrrolyl, trans-octahydro-1H-pyrrolo[3,4-b]pyridinyl, 2,6-diazaspiro[4.5]decanyl, 2,7-diazaspiro[4.5]decanyl, 1,7-diazaspiro[3.5]nonanyl, 1,6-diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, (4aR,8aR)- Decahydro-1,5-naphthilidinyl, 3,9-diazaspiro[5.5]undecanyl, (3aS,6aS)-octahydropyrrolo[2,3-c]pyrrolyl, 2,9-diazaspiro[6.6]tridecanyl, 3,8-diazabicyclo[4.2.0]octanyl, 3,7-diazabicyclo[4.2.0]octanyl, 9,9-dimethyl-3,7-diazabicyclo[3.3.1]nonanyl, cis-octahydropyrrolo[3,4-c]pyridinyl, cis-decahydro-1,7-naphthilidinyl, 2,7-diazabicyclo[4.2.0] Octanil, (4aS,7aS)-Octahydropyrrolo[3,4-b][1,4]oxazinyl, 2,6-Diazaspiro[3.4]octanil, 1,9-Diazaspiro[6.6]tridecanil, (4aS,8aS)-Decahydro-1,5-Naphthilidinyl, trans-Decahydro-1,7-Naphthiridine, (1S,2S)-2,5-Diazabicyclo[2.2.1]heptanil, t The group may be rans-decahydro-1,7-naphthilidinyl, rac-(4aR,8aR)-octahydro-2H-pyrido[4,3-b]morpholinyl, decahydro-1,6-naphthilidinyl, octahydro-1H-pyrrolo[3,2-c]pyridinyl, rac-(3aR,6aR)-octahydropyrrolo[2,3-c]pyrrolyl, or decahydropyrrolo[3,2-c]azepinyl. Preferably, the N heteroatom of the heterocyclyl group is X. 1 It is directly bonded to the 6-membered aromatic heterocycline group of formula (I) which includes [the specified element].

[0115] In embodiments where Z is a 5- to 13-membered non-aromatic heterocyclyl group, preferably Z is a 5- to 13-membered non-aromatic heterocyclyl group (i.e., a 5, 6, 7, 8, 9, 10, 11, 12, or 13-membered non-aromatic heterocyclyl group) comprising 1, 2, or 3 heteroatoms selected from N and O, where at least one of the heteroatoms is N, and where the 5- to 13-membered non-aromatic heterocyclyl group is optionally substituted with 1, 2, 3, or 4 substituents (e.g., 1, 2, or 3 substituents; or 1 or 2 substituents; or 1 substituent). In such embodiments, preferably the N heteroatom is X 1It is directly bonded to a 6-membered aromatic heterocyclyl group of formula (I) including . For example, Z is a 5- to 10-membered non-aromatic heterocyclyl group, preferably Z is a 5- to 10-membered non-aromatic heterocyclyl group (i.e., a 5, 6, 7, 8, 9, or 10-membered non-aromatic heterocyclyl group) containing 1, 2, or 3 heteroatoms selected from N and O, where at least one of the heteroatoms is N, and where the 5- to 10-membered non-aromatic heterocyclyl group is optionally substituted with 1, 2, 3, or 4 substituents (e.g., 1, 2, or 3 substituents; or 1 or 2 substituents; or 1 substituent). In such embodiments, preferably the N heteroatom is X 1 It is directly bonded to the 6-membered aromatic heterocycline group of formula (I) which includes [the specified element].

[0116] Alternatively, here Z is a 5-13 member non-aromatic heterocyclyl group, preferably a 6-10 member non-aromatic heterocyclyl group (i.e., a 6, 7, 8, 9, or 10 member non-aromatic heterocyclyl group) comprising 1, 2, or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and here the 6-10 member non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). More preferably, Z is a 6-10 member non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and the 6-10 member non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). More preferably, Z is a 6-10 member non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and the 6-10 member non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). More preferably, Z is a 6-10 member non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N and O, where at least one of the heteroatoms is N, and where the 6-10 member non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). In such embodiments, preferably, the N heteroatom is X 1 It is directly bonded to the 6-membered aromatic heterocycline group of formula (I) which includes [the specified element].

[0117] Alternatively, here Z is a 5- to 13-membered non-aromatic heterocyclyl group, preferably Z is a 5- to 8-membered non-aromatic heterocyclyl group (i.e., a 5, 6, 7, or 8-membered non-aromatic heterocyclyl group) comprising 1, 2, or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and here the 5- to 8-membered non-aromatic heterocyclyl group is optionally substituted with 1, 2, 3, or 4 substituents (e.g., 1, 2, or 3 substituents; or 1 or 2 substituents; or 1 substituent). More preferably, Z is a 5-8 member non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and the 5-8 member non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). More preferably, Z is a 5-8 member non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and the 5-8 member non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). More preferably, Z is a 5-8 member non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N and O, where at least one of the heteroatoms is N, and where the 5-8 member non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). In such embodiments, preferably, the N heteroatom is X 1 It is directly bonded to the 6-membered aromatic heterocycline group of formula (I) which includes [the specified element].

[0118] In one preferred embodiment, where Z is a 5- to 13-membered non-aromatic heterocyclyl group, preferably Z is a 6-membered non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and where the 6-membered non-aromatic heterocyclyl group is optionally substituted with 1, 2, 3, or 4 substituents (e.g., 1, 2, or 3 substituents; or 1 or 2 substituents; or 1 substituent). More preferably Z is a 6-membered non-aromatic heterocyclyl group comprising 2 or 3 heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and where the 6-membered non-aromatic heterocyclyl group is optionally substituted with 1, 2, 3, or 4 substituents (e.g., 1, 2, or 3 substituents; or 1 or 2 substituents; or 1 substituent). More preferably, Z is a six-membered non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N, O, and S, where at least one of the heteroatoms is N, and the six-membered non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). Even more preferably, Z is a six-membered non-aromatic heterocyclyl group comprising two or three heteroatoms selected from N and O, where at least one of the heteroatoms is N, and the six-membered non-aromatic heterocyclyl group is optionally substituted with one, two, three, or four substituents (e.g., one, two, or three substituents; or one or two substituents; or one substituent). In such embodiments, preferably, the N heteroatom is X 1 It is directly bonded to the 6-membered aromatic heterocycline group of formula (I) which includes [the specified element].

[0119] In embodiments where Z is optionally substituted (for example, optionally substituted with one, two, three, or four substituents; or optionally substituted with one, two, or three substituents; or optionally substituted with one or two substituents; or optionally substituted with one substituent), each substituent is a halogen; each substituent is a halogen, -OH, and -OC, which is optionally substituted with one, two, or three halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 They may be independently selected from the group consisting of alkyl groups. Preferably, each substituent is a halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-4 Independently selected from the group consisting of alkyl groups. More preferably, each substituent is a halogen; a halogen, -OH, and -OC, which are optionally substituted with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Alkyl; as well as halogens, -OH, and -OC optionally substituted with 1, 2, or 3 halogens. 1-3 -OC optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4Independently selected from the group consisting of alkyl groups. More preferably, each substituent is optionally substituted with halogen; halogen and 1, 2, or 3 halogens -OC 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Alkyl; and optionally substituted with halogens and 1, 2, or 3 halogens -OC 1-3 -OC optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Independently selected from the group consisting of alkyls (for example, each substituent is independently optionally substituted with a halogen and 1, 2, or 3 halogens -OC) 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 (It is alkyl). More preferably, each substituent is a halogen; OC optionally substituted with 1, 2, or 3 fluorine atoms. 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Alkyl; and -OC optionally substituted with F and 1, 2, or 3 F atoms. 1-3 -OC optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Independently selected from the group consisting of alkyls (for example, each substituent is independently optionally substituted with F and 1, 2, or 3 F atoms -OC) 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 (It is alkyl.)

[0120] Alternatively, each substituent may be a halogen; each substituent may be optionally substituted with a halogen and 1, 2, or 3 halogens -OC 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 Alkyl; and -OC, where each substituent is optionally substituted with a halogen and one, two, or three halogens. 1-3-OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-4 Independently selected from the group consisting of alkyl groups (for example, each substituent is independently substituted with a halogen and one, two, or three halogens -OC) 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 (It is alkyl). More preferably, each substituent is a halogen; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and methoxys optionally substituted with one, two, or three halogens -C 1-4 Alkyl; and -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Independently selected from the group consisting of alkyl groups. More preferably, each substituent is a halogen; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy groups in which each substituent is optionally substituted with F and one, two, or three F atoms -C 1-4 Alkyl; and -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl and methoxy molecules, each substituent optionally substituted with F and one, two, or three F atoms. 1-4 It is independently selected from the group consisting of alkyl groups.

[0121] In another preferred embodiment, each substituent of Z is independently selected from the group consisting of halogens; methyl atoms optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy atoms optionally substituted with F and one, two, or three F atoms; and methoxy atoms optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy atoms optionally substituted with F and one, two, or three F atoms (for example, each substituent is independently; methyl atoms optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy atoms optionally substituted with F and one, two, or three F atoms).

[0122] In one preferred embodiment, where Z is a 5-13 member non-aromatic heterocyclyl group, preferably Z is [ka] : is (or preferably, Z is, [ka] (and more preferably, Z is [ka] (and) Here, [ka] This represents a connection point.

[0123] m may be 0, 1, 2, or 3. Preferably, m is 0, 1, or 2. More preferably, m is 1 or 2.

[0124] r may be 0, 1, 2, or 3. Preferably, r is 0, 1, or 2. In one embodiment, preferably r is 1 or 2. In another embodiment, preferably r is 0 or 1.

[0125] s may be 0, 1, 2, or 3. Preferably, s is 0, 1, or 2. In one embodiment, preferably s is 1 or 2. In one embodiment, preferably s is 0 or 1. More preferably s is 0.

[0126] R 12 -OC is a compound in which hydrogen and each substituent is optionally substituted with a halogen and one, two, or three halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 A selection may be made from the group consisting of alkyl groups. Preferably, R 12 -OC is a compound in which hydrogen and each substituent is optionally substituted with a halogen and one, two, or three halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 Selected from the group consisting of alkyl groups. More preferably, R 12 -C 1-4 Selected from the group consisting of alkyl groups. More preferably, R 12 -C is optionally substituted with one substituent selected from the group consisting of hydrogen and halogens and methoxy molecules optionally substituted with 1, 2, or 3 halogens (e.g., 1, 2, or 3 F atoms). 1-4 Selected from the group consisting of alkyl groups. More preferably, R 12 -OC is a compound in which each substituent is optionally substituted with a halogen and one, two, or three halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 Selected from the group consisting of alkyl groups. More preferably, R 12 R is selected from the group consisting of hydrogen and methyl. More preferably, 12 is hydrogen. More preferably, R12 It is methyl.

[0127] In one preferred embodiment, Z is [ka] Preferably, Z is [ka] Preferably, Z is [ka] That is the case.

[0128] If present, each R 13 Halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; NR c R d ; and -OCs in which each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 They are independently selected from the group consisting of cycloalkyls; or, when two substituents are in adjacent ring positions, they contain a C heteroatom selected from the group consisting of O and N, together with the atom to which they are bonded. 3-6 They may be linked to form a cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group, where the C 3-6Cycloalkyl groups or 4-6 member non-aromatic heterocyclyl groups are each substituted with a halogen; each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups; R c and R d -C is a hydrogen atom; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-6 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 Selected from the group consisting of cycloalkyl groups.

[0129] Preferably, two substituents located in adjacent ring positions constitute one R 12 and one R 13 Alternatively, two substituents in adjacent ring positions are both R 13 That is the case.

[0130] Alternatively, m is 0 or 1, r is 2 or 3, and there are two R 13 When the group is in an adjacent ring position, the two R 13 These include a C atom, along with the atom to which they are bonded, which contains one heteroatom selected from the group consisting of O and N. 3-6 They are linked to form a cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group, where the C 3-6Cycloalkyl groups or 4- to 6-membered non-aromatic heterocyclyl groups (i.e., 4, 5, or 6-membered non-aromatic heterocyclyl groups) are defined as follows: each substituent is a halogen; each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens (-OC). 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups. Preferably, two R 13 The base is connected, C 3-6 A cycloalkyl group, for example, preferably an unsubstituted cyclopropyl group, is formed.

[0131] Alternatively, r is 1, 2, or 3, and one R 13 The base is NR 12 When R is in an adjacent ring position, 13 and R 12 They are linked together with the atom to which they are bonded so that they form a 5 or 6-membered non-aromatic heterocyclyl group containing one N heteroatom and optionally one heteroatom selected from the group consisting of O and N, where each substituent is a halogen; each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens -OC 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups; and If present, each R 14 is a halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is independently selected from the group consisting of alkyl groups.

[0132] In one preferred embodiment, if present, each R 13 Independently, NR c R d Alternatively, each substituent may be optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens in an -OC molecule. 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 It is cycloalkyl. In one preferred embodiment, each R 13 Independently, NR c R d That is the case.

[0133] More preferably, each R 13 These are independently -OC molecules, each substituent optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 It is a cycloalkyl group. More preferably, each R 13 These are independently, preferably unsubstituted cyclopropyl compounds.

[0134] In one embodiment, R cis hydrogen. In a second embodiment, R c -C 1-6 It is alkyl. In a third embodiment, R c This refers to a C molecule in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 It is a cycloalkyl group.

[0135] Preferably, R c is non-substituted -C 1-6 Alkyl groups, such as methyl, ethyl, and propyl, particularly methyl and ethyl, and especially methyl.

[0136] Preferably, R c is unsubstituted C 3-6 Cycloalkyl groups, such as cyclopropyl, cyclobutyl, and cyclopentyl, particularly cyclopropyl.

[0137] In one embodiment, R d is hydrogen. In a second embodiment, R d -C 1-6 It is alkyl. In a third embodiment, R d This refers to a C molecule in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OH, -OCH3, and -OCF3. 3-6 It is a cycloalkyl group.

[0138] Preferably, R d is non-substituted -C 1-6 Alkyl groups, such as methyl, ethyl, and propyl, particularly methyl and ethyl, and especially methyl.

[0139] Preferably, R dis unsubstituted C 3-6 Cycloalkyl groups, such as cyclopropyl, cyclobutyl, and cyclopentyl, particularly cyclopropyl.

[0140] In one embodiment, R c is hydrogen, and R d is preferably an unsubstituted methyl group. In a second embodiment, R c and R d Each of these is preferably an unsubstituted methyl group. In a third embodiment, R c and R d Each of them is hydrogen.

[0141] Alternatively, if present, each R 13 is a halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 May they be independently selected from the group consisting of alkyl groups? Alternatively, m is 0 or 1, r is 2 or 3, and there are two R 13 When the group is in an adjacent ring position, the two R 13 They are linked together with the atom to which they are bonded to form a C4-6 cycloalkyl group (i.e., a cyclobutyl, cyclopentyl, or cyclohexyl group) or a 4- to 6-membered non-aromatic heterocyclyl group (i.e., a 4, 5, or 6-membered non-aromatic heterocyclyl group) which contains one heteroatom selected from the group consisting of O and N, where the C4-6 cycloalkyl group or 4- to 6-membered non-aromatic heterocyclyl group is optionally substituted with halogens; or with halogens, -OH, and 1, 2, or 3 halogens. 1-3-C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups; Alternatively, r is 1, 2, or 3, and one R 13 The base is NR 12 When R is in an adjacent ring position, 13 and R 12 They are linked together with the atom to which they are bonded so that they form a 5 or 6-membered non-aromatic heterocyclyl group containing one N heteroatom and optionally one heteroatom selected from the group consisting of O and N, where each substituent is a halogen; each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens -OC 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups.

[0142] Preferably, if present, each R 13 is a halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Independently selected from the group consisting of alkyl groups. Preferably, if present, each R 13 This is an -OC molecule in which each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is alkyl. More preferably, each R 13 These are independently methyl.

[0143] If present, each R 14 is a halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 They may be independently selected from the group consisting of alkyl groups.

[0144] In one preferred embodiment, each R 13 (and / or two R 13 Each substituent of a C4-6 cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group formed from the group, or NR 12 and R 13Each substituent of the 5-6 member non-aromatic heterocyclyl group formed from the group; or each R 14 ) is a halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-4 Independently selected from the group consisting of alkyl groups. More preferably, each R 13 (and / or two R 13 Each substituent of a C4-6 cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group formed from the group, or NR 12 and R 13 Each substituent of the 5-6 member non-aromatic heterocyclyl group formed from the group; or each R 14 ) is a halogen; optionally substituted with halogens and 1, 2, or 3 halogens -OC 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Alkyl; and optionally substituted with halogens and 1, 2, or 3 halogens -OC 1-3 -OC optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Independently selected from the group consisting of alkyls (for example, each substituent is independently optionally substituted with a halogen and 1, 2, or 3 halogens -OC) 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 (It is alkyl). More preferably, each R 13 (and / or two R 13 Each substituent of a C4-6 cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group formed from the group, or NR 12 and R 13Each substituent of the 5-6 member non-aromatic heterocyclyl group formed from the group; or each R 14 ) is a halogen; optionally substituted with 1, 2, or 3 fluorine atoms -OC 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Alkyl; and -OC optionally substituted with F and 1, 2, or 3 F atoms. 1-3 -OC optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Independently selected from the group consisting of alkyls (for example, each substituent is independently optionally substituted with F and 1, 2, or 3 F atoms -OC) 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 (It is alkyl.)

[0145] Alternatively, each R 13 (and / or two R 13 Each substituent of a C4-6 cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group formed from the group, or NR 12 and R 13 Each substituent of the 5-6 member non-aromatic heterocyclyl group formed from the group; or each R 14 ) is a halogen; each substituent is optionally substituted with a halogen and 1, 2, or 3 halogens -OC 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 Alkyl; and -OC, where each substituent is optionally substituted with a halogen and one, two, or three halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-4 Independently selected from the group consisting of alkyl groups (for example, each substituent is independently substituted with a halogen and one, two, or three halogens -OC) 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups1-4 is alkyl). More preferably, each R 13 (and / or each substituent of a C4-6 cycloalkyl group or 4-6 member non-aromatic heterocyclyl group formed from two R 13 groups, or each substituent of a 5-6 member non-aromatic heterocyclyl group formed from N-R 12 and R 13 groups; or each R 14 ) is halogen; -C 1-4 alkyl optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen; and methoxy optionally substituted by halogen and one, two, or three halogens; and -O-C 1-4 alkyl optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen; and methoxy optionally substituted by halogen and one, two, or three halogens. Even more preferably, each R 13 (and / or each substituent of a C4-6 cycloalkyl group or 4-6 member non-aromatic heterocyclyl group formed from two R 13 groups, or each substituent of a 5-6 member non-aromatic heterocyclyl group formed from N-R 12 and R 13 groups; or each R 14 ) is halogen; -C 1-4 alkyl optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen; and methoxy optionally substituted by F and one, two, or three F atoms; and -O-C 1-4 alkyl optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen; and methoxy optionally substituted by F and one, two, or three F atoms.

[0146] In a preferred embodiment, Z is

Chemical formula

[0147] In one preferred embodiment, Z is [ka] And here, [ka] This represents a point of connection, m is 1 or 2; r is 0, 1, or 2. If present, each R 13is a halogen; each substituent is optionally substituted with a halogen, -OH, and -OC with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; NR c R d , as well as -OC molecules in which each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 A cycloalkyl group is independently selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0148] Z is -NR 10 R 11 In one possible embodiment, R 10 is hydrogen and -C 1-4 A selection may be made from the group consisting of alkyl groups. Preferably, R 10 It is either hydrogen or methyl.

[0149] Z is -NR 10 R 11 In one possible embodiment, R 11 R may be a 5-10 member non-aromatic heterocyclyl group (i.e., a 5, 6, 7, 8, 9, or 10 member non-aromatic heterocyclyl group) comprising 1, 2, or 3 heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and the 5-10 member non-aromatic heterocyclyl group is optionally substituted with 1, 2, 3, or 4 substituents (e.g., 1, 2, or 3 substituents; or 1 or 2 substituents; or 1 substituent). Preferably, R 11is a 5 or 6-membered non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with 1, 2, or 3 substituents. More preferably, R 11 This is a 5 or 6-membered non-aromatic heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N and O, and the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with 1, 2, or 3 substituents.

[0150] Alternatively, R 11 is a 5 or 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N, O, and S (e.g., one heteroatom), wherein at least one of the heteroatoms is N, and the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one, two, or three substituents. Preferably, R 11 is a 5 or 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N and O (e.g., one heteroatom), wherein at least one of the heteroatoms is N, and the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one, two, or three substituents.

[0151] In one preferred embodiment, R 11 This is a five-membered non-aromatic heterocyclyl group containing one or two N heteroatoms, where the five or six-membered non-aromatic heterocyclyl group is optionally substituted with one, two, or three substituents.

[0152] In one preferred embodiment, R 11 is a 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N and O, wherein at least one of the heteroatoms is N, and wherein the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one, two, or three substituents.

[0153] One preferred embodiment, R 11 is a 5 or 6-membered non-aromatic heterocyclyl group comprising 1, 2, or 3 heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two (e.g., one) substituents. More preferably, R 11 R is a 5 or 6-membered non-aromatic heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N and O, where the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two (e.g., one) substituents. Alternatively, R 11 R is a 5 or 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N, O, and S, wherein at least one of the heteroatoms is N, and the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two (e.g., one) substituents. 11 is a 5 or 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N and O, wherein at least one of the heteroatoms is N, and wherein the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two (e.g., one) substituents.

[0154] In one preferred embodiment, R 11 is a five-membered non-aromatic heterocyclyl group containing one or two N heteroatoms, where the five or six-membered non-aromatic heterocyclyl group is optionally substituted with one or two (e.g., one) substituents.

[0155] In one preferred embodiment, R 11 is a 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N and O, wherein at least one of the heteroatoms is N, and wherein the 5 or 6-membered non-aromatic heterocyclyl group is optionally substituted with one or two (e.g., one) substituents.

[0156] R 11In embodiments where the substituents are optionally substituted (for example, optionally substituted with 1, 2, 3, or 4 substituents; or optionally substituted with 1, 2, or 3 substituents; or optionally substituted with 1 or 2 substituents; or optionally substituted with 1 substituent), each substituent is a halogen; -OH; and -OC where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 They may be independently selected from the group consisting of alkyl groups. Preferably, each substituent is a halogen; -OH; and each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens in the -OC group. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 Alkyl; and -OC, where each substituent is optionally substituted with a halogen, -OH, and 1, 2, or 3 halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-4 Independently selected from the group consisting of alkyl groups. More preferably, each substituent is a halogen; -OH; halogen, -OH, and -OC optionally substituted with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4 Alkyl; as well as halogens, -OH, and -OC optionally substituted with 1, 2, or 3 halogens. 1-3 -OC optionally substituted with one substituent selected from the group consisting of alkyl groups 1-4It is independently selected from the group consisting of alkyl. More preferably, each substituent is halogen; -OC optionally substituted by halogen and one, two, or three halogens 1-3 -C optionally substituted by one substituent selected from the group consisting of alkyl 1-4 alkyl; and -O-C optionally substituted by halogen and one, two, or three halogens 1-3 -O-C optionally substituted by one substituent selected from the group consisting of alkyl 1-4 It is independently selected from the group consisting of alkyl (for example, each substituent is independently -OC optionally substituted by halogen and one, two, or three halogens 1-3 -C optionally substituted by one substituent selected from the group consisting of alkyl 1-4 alkyl).

[0157] In a preferred embodiment, each substituent is halogen; -OC optionally substituted by F and one, two, or three F atoms 1-3 -C optionally substituted by one substituent selected from the group consisting of alkyl 1-4 alkyl; and -O-C optionally substituted by F and one, two, or three F atoms 1-3 -O-C optionally substituted by one substituent selected from the group consisting of alkyl 1-4 It is independently selected from the group consisting of alkyl (for example, each substituent is independently -OC optionally substituted by F and one, two, or three F atoms 1-3 -C optionally substituted by one substituent selected from the group consisting of alkyl 1-4 alkyl).

[0158] Alternatively, each substituent is halogen; -OC in which each substituent is optionally substituted by halogen and one, two, or three halogens 1-3 -C optionally substituted by one, two, or three substituents independently selected from the group consisting of alkyl 1-4Alkyl; and -OC, where each substituent is optionally substituted with a halogen and one, two, or three halogens. 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-4 Independently selected from the group consisting of alkyl groups (for example, each substituent is independently substituted with a halogen and one, two, or three halogens -OC) 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-4 (It is alkyl). More preferably, each substituent is a halogen; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and methoxys optionally substituted with one, two, or three halogens -C 1-4 Alkyl; and -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Independently selected from the group consisting of alkyl groups. More preferably, each substituent is a halogen; each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of methoxy groups in which each substituent is optionally substituted with F and one, two, or three F atoms -C 1-4 Alkyl; and -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl and methoxy molecules, each substituent optionally substituted with F and one, two, or three F atoms. 1-4 It is independently selected from the group consisting of alkyl groups.

[0159] In one embodiment, Z is [ka] Selected from the group consisting of TIFF0007843754000033.tif106170:, where, [ka] This represents a connection point.

[0160] For example, Z is [ka] Selected from the group consisting of :, where, [ka] This represents a connection point.

[0161] Alternatively, Z is, [ka] The group consisting of TIFF0007843754000038.tif120170: may also be selected, where, [ka] This represents a connection point.

[0162] For example, Z is [ka] Selected from the group consisting of :, where, [ka] This represents a connection point.

[0163] In one preferred embodiment, Z is [ka] Selected from the group consisting of TIFF0007843754000043.tif115170:, where, [ka] This represents a connection point.

[0164] For example, Z is [ka] Selected from the group consisting of :, where, [ka] This represents a connection point.

[0165] In one preferred embodiment, Z is [ka] Selected from the group consisting of TIFF0007843754000048.tif177170:, where, [ka] This represents a connection point.

[0166] In one particularly preferred embodiment, Z is [ka] Selected from the group consisting of :, where, [ka] This represents a connection point.

[0167] In one particularly preferred embodiment, Z is [ka] : and here, [ka] This represents a connection point.

[0168] In one particularly preferred embodiment, Z is [ka] : and here, [ka] This represents a connection point.

[0169] In one particularly preferred embodiment, the compound of formula (I) is the compound of formula (Ie), where each group may be as defined above: [ka] .

[0170] In another particularly preferred embodiment, the compound of formula (I) is the compound of formula (If), where each group may be as defined above: [ka] .

[0171] In another particularly preferred embodiment, the compound of formula (I) is the compound of formula (Ig), where each group may be as defined above: [ka] .

[0172] In another particularly preferred embodiment, the compound of formula (I) is the compound of formula (Ih), where each group may be as defined above: [ka] .

[0173] In another particularly preferred embodiment, the compound of formula (I) is the compound of formula (Ij), where each group may be as defined above: [ka] .

[0174] In another particularly preferred embodiment, the compound of formula (I) is the compound of formula (Ik), where each group may be as defined above: [ka] .

[0175] In one particularly preferred embodiment, the compound of formula (I) is the compound of formula (Im), where each group may be as defined above: [ka] .

[0176] In one particularly preferred embodiment, the compound of formula (I) is the compound of formula (In), where each group may be as defined above: [ka] .

[0177] In another particularly preferred embodiment, the compound of formula (I) is the compound of formula (Io), where each group may be as defined above: [ka] .

[0178] In one particularly preferred embodiment, the compound of formula (I) is the compound of formula (Ip), where each group is as defined above: [ka] .

[0179] In one particularly preferred embodiment, the compound of formula (I) is the compound of formula (Iq): [ka] (In the formula: R 3aThis refers to a C atom that is optionally substituted with H or one, two, or three substituents, each of which is independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 It is alkyl; R 8a C is a halogen or a C atom in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OCH3, and -OCF3. 1-4 It is alkyl; ra is 0, 1, or 2; m a is either 1 or 2; R 12a This refers to a C atom that is optionally substituted with H or one, two, or three substituents, each of which is independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 alkyl and If present, each R 13a This refers to a C molecule in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 Alkyl; and C, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -CH3, -OCH3, and -OCF3. 3-6 Independently selected from the group consisting of cycloalkyls; or Ra is 2 and there are two R 13a When the group is in an adjacent ring position, the two R 13a These are atoms to which they are bonded, and each substituent is a halogen; each substituent is a halogen, -OH, and -OC, which are optionally substituted with 1, 2, or 3 halogens. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 C optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups 3-6 (They are linked to form a cycloalkyl group.)

[0180] In one embodiment, R 3a is H. In a second example, R 3a C 1-4 Alkyl, for example, preferably unsubstituted methyl, ethyl, or propyl, for example, preferably unsubstituted methyl.

[0181] In one embodiment, R 8a is a halogen, for example, Cl, Br, or F, in particular Cl. In a second embodiment, R 8a This refers to a C molecule in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OCH3, and -OCF3. 1-4 Alkyl; in particular, R 8a This is CF3.

[0182] In one embodiment, ra is 0. In a second embodiment, ra is 1. In a third embodiment, ra is 2.

[0183] In one embodiment, m a In the second embodiment, m a The answer is 2.

[0184] In one embodiment, R 12a is H. In a second example, R 12a C 1-4 Alkyl groups, for example, preferably unsubstituted methyl, ethyl, or propyl, particularly preferably unsubstituted methyl or ethyl, and particularly preferably unsubstituted methyl.

[0185] In one embodiment, each R 13a Independently, C 1-4 Alkyl, for example, preferably unsubstituted methyl, ethyl, or propyl, particularly preferably unsubstituted methyl or ethyl, particularly preferably unsubstituted methyl. In the second embodiment, each R 13a Independently, C 3-6Cycloalkyl groups, for example, preferably unsubstituted cyclopropyl, cyclobutyl, or cyclopentyl, and particularly preferably unsubstituted cyclopropyl.

[0186] In one embodiment, ra is 2 and there are two R 13a The base is located in an adjacent ring position, and the two R 13a They are, together with the atoms to which they are bonded, and they are C 3-6 A cycloalkyl group, for example, preferably an unsubstituted cyclopropyl, cyclobutyl, or cyclopentyl, is linked to form a cycloalkyl group, particularly preferably an unsubstituted cyclopropyl group.

[0187] In one preferred embodiment, the compound is selected from the group consisting of Example Compounds 1 to 112.

[0188] In one particularly preferred embodiment, the compound of formula (I) is: 1-{5-chloro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyridine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-(5-chloro-2-{3,6-diazabicyclo[3.2.0]heptan-3-yl}pyrimidine-4-yl)-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-(2-{3,6-diazabicyclo[3.2.0]heptan-3-yl}-5-fluoropyrimidine-4-yl)-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-({2-methylimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-(2-{3,6-diazabicyclo[3.2.0]heptan-3-yl}-5-fluoropyrimidine-4-yl)-N-({2-methylimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-{5-fluoro-2-[methyl(pyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-fluoro-2-(pyrroridine-3-ylamino)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-fluoro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}-N-methylazetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-({2-methylimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-methoxypyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-methoxypyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-({6-fluoroimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-({6-chloroimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-methoxypyrimidine-4-yl]-N-(1-{2-methylimidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(1-{2-methylimidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-fluoro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-fluoro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-fluoro-2-(piperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(piperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methoxy-2-(piperazine-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; 1-{5-fluoro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-fluoro-2-[methyl(pyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[methyl(pyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5S)-3,5-dimethylpiperazine-1-yl]-5-methoxypyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5S)-3,5-dimethylpiperazine-1-yl]-5-chloropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5S)-3,5-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide 1-{2-[(3S,5S)-3,5-dimethylpiperazine-1-yl]-5-methoxypyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5R)-3,5-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5R)-3,5-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3S,5S)-3,5-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide 1-[5-fluoro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[methyl(1-methylpyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[methyl(1-methylpyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{8-fluoroimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methoxy-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-3-methylazetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methyl-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2R)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[3-(fluoromethyl)-4-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-ethylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[4-(propan-2-yl)piperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[4-(2-methoxyethyl)piperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; (3R)-1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; (3S)-1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)piperidine-4-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(2S,3R)-2,3-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[3-(methoxymethyl)-4-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-(5-fluoro-2-{6-methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl}pyrimidine-4-yl)-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{2-[(3S)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3S)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-methoxypyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)pyrrolidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-3-methylazetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; (3R)-1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; (3S)-1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)piperidine-4-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyridine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyridine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyridine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{2-[(2S)-2,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(2S,5R)-2,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2R,5R)-2,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(2S,5R)-2,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; and 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{[1,2,4]triazolo[4,3-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; The group comprises esters, amides, carbamates, and salts of any one of these that are pharmaceutically acceptable, and is selected from the group consisting of salts of such esters, amides, and carbamates.

[0189] In one particularly preferred embodiment, the compound of formula (I) is: N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)quinazoline-4-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-4-yl)azetidine-3-carboxamide; 1-(5-chloro-6-methyl-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(6-methyl-2-(4-methyl-1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(6-methyl-2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide; 1-(2-(1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(piperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methyl-1-(2-(4-methyl-1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; (R)-1-(5-chloro-2-(3-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methyl-1-(2-(2-methylpiperazine-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; (S)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(2-methylpiperazine-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(3,3-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(4-aminopiperidine-1-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(4,7-diazaspiro[2.5]octan-7-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(4-aminoazepan-1-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(3,8-diazabicyclo[3.2.1]octan-3-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(2,3-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methyl-1-(2-(2-methylpiperazine-1-yl)-5-(trifluoromethyl)pyrimidine-4-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl)-N-ethyl-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(3-ethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (R)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (R)-1-(5-chloro-2-(2,4-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-1-(5-chloro-2-(3-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-1-(5-chloro-2-(3,4-dimethylpiperazin-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (R)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(2,3-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-methylpiperazin-1-yl)pyrimidine-4-yl)-N-ethyl-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(2-(3,8-diazabicyclo[3.2.1]octan-3-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propane-2-yl)azetidine-3-carboxamide; 1-(2-(2,5-diazabicyclo[4.1.0]heptan-2-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-ethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-ethylpiperazin-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide: 1-(5-chloro-2-(2,2-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(4,7-diazaspiro[2.5]octan-4-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-((2S,5S)-2,5-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-((2S,5S)-2,4,5-trimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-((2S,5R)-2,5-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; and 1-(5-chloro-2-((2S,5R)-2,4,5-trimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; The group comprises esters, amides, carbamates, and salts of any one of these that are pharmaceutically acceptable, and is selected from the group consisting of salts of such esters, amides, and carbamates.

[0190] Depending on the substituents present in the compound of the present invention, the compound may form an ester, amide, carbamate, or a salt containing an ester, amide, or carbamate. Preferably, if the compound is in the form of an ester, amide, carbamate, and / or salt, it is a pharmaceutically acceptable ester, amide, carbamate, and / or salt.

[0191] The compounds of the present invention may also be in the form of pharmaceutically acceptable salts. Salts of the compounds of the present invention that are suitable for pharmaceutical use have pharmaceutically acceptable counterions. However, salts having pharmaceutically unacceptable counterions are within the scope of the present invention, for example, for use as intermediates in the preparation of the compounds of the present invention and their pharmaceutically acceptable salts. In one embodiment, the compounds of the present invention are not in the form of pharmaceutically acceptable salts.

[0192] Suitable salts according to the present invention include those formed with organic or inorganic acids or bases. In particular, suitable salts formed with acids according to the present invention include those formed with mineral acids, strong organic carboxylic acids, such as alkane carboxylic acids with 1 to 4 carbon atoms that are unsubstituted or substituted with halogens, such as saturated or unsaturated dicarboxylic acids, such as hydroxycarboxylic acids, such as amino acids, or with organic sulfonic acids, such as (C1-C4)-alkyl or aryl-sulfonic acids that are unsubstituted or substituted with halogens, for example. Pharmaceutically acceptable acid addition salts include those formed from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, citric acid, tartaric acid, acetic acid, phosphoric acid, lactic acid, pyruvic acid, acetic acid, trifluoroacetic acid, succinic acid, perchloric acid, fumaric acid, maleic acid, glycolic acid, lactic acid, salicylic acid, oxaloacetic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, formic acid, benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, isethionic acid, ascorbic acid, malic acid, phthalic acid, aspartic acid, and glutamic acid, lysine, and arginine. Other acids may or may not be pharmaceutically acceptable in themselves, but they may be useful as intermediates in obtaining the compounds of the present invention and their pharmaceutically acceptable acid addition salts.

[0193] Pharmaceutically acceptable base salts include ammonium salts, alkali metal salts such as potassium and sodium salts, alkaline earth metal salts such as calcium and magnesium salts, and organic bases such as dicyclohexylamine and N-methyl-D-glucan. mosquito The salts include mine, morpholine, thiomorpholine, piperidine, pyrrolidine, mono-, di-, or tri-lower alkylamines, such as ethyl-, tert-butyl-, diethyl-, diisopropyl-, triethyl-, tributyl-, or dimethyl-propylamine, or mono-, di-, or trihydroxy lower alkylamines, such as mono-, di-, or triethanolamine. Corresponding intramolecular salts may be further formed.

[0194] The compounds of the present invention may have suitable groups that can be converted to esters, amides, or carbamates. Therefore, typical ester and amide groups formed from acidic groups in the compounds of the present invention have -COOR G ,-CONR G 2, -SO2OR G , or -SO2N(R G )2 is included, while the compound of the present invention contains -OH or -NHR G Typical ester, amide, and carbamate groups formed from this group include -OC(O)R G , -NR G C(O)R G , -NR G CO2R G , -OSO2R G , and -NR G SO2R G This includes, in this case, R G C 1-8 Alkyl, C 2-8 Alkenil, C 2-8 Alkinyl, C 3-8 Cycloalkyl, and C 3-8 Cycloalkyl C 1-8 Alkyl, Halo C 1-8 Alkyl, Dihalo C 1-8 Alkyl, Trihalo C 1-8 Alkyl, phenyl, and phenyl C 1-4Selected from the group consisting of alkyl groups; more preferably, R G C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-8 Cycloalkyl, and C 3-8 Cycloalkyl C 1-6 Selected from the group consisting of alkyl groups.

[0195] Those skilled in organic chemistry will understand that many organic compounds can form complexes with solvents in which they react or precipitate or crystallize. These complexes are known as “solvates.” For example, a complex with water is known as a “hydrate.” Solvates, such as hydrates, exist when an active pharmaceutical ingredient (API) incorporates a solvent, such as water, into its crystal lattice in either stoichiometric or non-stoichiometric amounts. APIs are routinely screened for the presence of hydrates because they may be found at any stage of the drug manufacturing process or during storage of the API or dosage form. Solvates are described in the literature of S. Byrn et al., Pharmaceutical Research, 1995. 12(7): pp. 954-954, incorporated herein by reference, and in the literature of R. Liu, Water-Insoluble Drug Formulation, 2nd edition, CRC Press, p. 553. Therefore, it will be understood by those skilled in the art that the compounds of the present invention may thus exist in the form of solvates. Solvates of the compounds of the present invention that are suitable for pharmaceutical use are solvates in which the associated solvent is pharmaceutically acceptable. For example, hydrates are an example of pharmaceutically acceptable solvates. However, solvates having an associated solvent that is not pharmaceutically acceptable may be used as intermediates in the preparation of the compounds according to the present invention.

[0196] A suitable pharmaceutically acceptable derivative of the compound of the present invention is a salt.

[0197] (Use of the compound of the present invention) Inhibition of human NMT has been proposed as a target for treating or preventing various diseases or disorders as described above.

[0198] Since the compounds of the present invention are NMT inhibitors, the compounds of the present invention can be used in the treatment of diseases or disorders associated with NMT activity, or can be used in the treatment of diseases or disorders by targeting NMT activity in (e.g., hyperproliferative diseases (e.g., cancer) and viral infections (e.g., picornavirus infections)). Accordingly, the present invention provides compounds of the present invention for use as pharmaceuticals, or pharmaceutical compositions comprising compounds of the present invention and pharmaceutically acceptable carriers. The present invention also provides compounds of the present invention for use in the treatment or prevention of diseases or disorders in which inhibition of N-myristoyltransferase provides a therapeutic or preventive effect, or pharmaceutical compositions comprising compounds of the present invention and pharmaceutically acceptable carriers. The present invention also provides compounds of the present invention for use in the treatment of diseases or disorders in which inhibition of N-myristoyltransferase provides a therapeutic effect, or pharmaceutical compositions comprising compounds of the present invention and pharmaceutically acceptable carriers. The present invention also provides compounds of the present invention for use in the prevention of diseases or disorders in which inhibition of N-myristoyltransferase provides a preventive effect, or pharmaceutical compositions comprising compounds of the present invention and pharmaceutically acceptable carriers.

[0199] The present invention also provides a method for treating or preventing a disease or disorder in a subject (e.g., a mammal, e.g., a human) in which inhibition of N-myristoyltransferase in the subject results in a therapeutic or preventive effect, the method comprising administering to the subject a therapeutically effective amount of the compound according to the present invention, or a pharmaceutical composition comprising the compound according to the present invention and a pharmaceutically acceptable carrier. The present invention also provides a method for treating a disease or disorder in a subject (e.g., a mammal, e.g., a human) in which inhibition of N-myristoyltransferase in the subject results in a therapeutic effect, the method comprising administering to the subject a therapeutically effective amount of the compound according to the present invention, or a pharmaceutical composition comprising the compound according to the present invention and a pharmaceutically acceptable carrier. The present invention also provides a method for preventing a disease or disorder in a subject (e.g., a mammal, e.g., a human) in which inhibition of N-myristoyltransferase in the subject results in a preventive effect, the method comprising administering to the subject a preventively effective amount of the compound according to the present invention, or a pharmaceutical composition comprising the compound according to the present invention and a pharmaceutically acceptable carrier.

[0200] The present invention also provides the use of compounds according to the present invention for the manufacture of pharmaceuticals for the treatment or prevention of diseases or disorders in which inhibition of N-myristoyltransferase provides a therapeutic or preventive effect. The present invention also provides the use of compounds according to the present invention for the manufacture of pharmaceuticals for the treatment of diseases or disorders in which inhibition of N-myristoyltransferase provides a therapeutic effect. The present invention also provides the use of compounds according to the present invention for the manufacture of pharmaceuticals for the prevention of diseases or disorders in which inhibition of N-myristoyltransferase provides a preventive effect.

[0201] Diseases and disorders for which inhibition of N-myristoyltransferase provides therapeutic or preventive effects include: hyperproliferative disorders, viral infections, neurological disorders, ischemia, osteoporosis, diabetes, autoimmune diseases, and inflammatory diseases. Therefore, the compounds of the present invention are used in the treatment or prevention of these disorders / diseases.

[0202] Diseases and disorders for which inhibition of N-myristoyltransferase provides therapeutic or preventive effects include: microbial infections; for example, fungal infections, and protozoan infections, such as malaria, leishmaniasis, human African trypanosomiasis (sleeping sickness), and American trypanosomiasis (Chagas disease).

[0203] It is also expected that the compounds of the present invention will be particularly useful in targeting diseases in specific patient populations, namely, diseases that are expected to be particularly affected by the inhibition of N-myristoyltransferase, in particular human N-myristoyltransferase. Such diseases include hyperproliferative disorders, particularly cancers, such as hematological malignancies (e.g., lymphomas, especially B-cell lymphomas (e.g., high-grade mantle lymphoma, follicular lymphoma, plasmablastic lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma), myelomas (e.g., multiple myeloma), or leukemias (e.g., chronic lymphocytic leukemia, AML, and B-acute lymphocytic leukemia)), or solid tumors (e.g., brain cancer, lung cancer, breast cancer (e.g., triple-negative breast cancer or invasive breast cancer), prostate cancer, ovarian cancer, colorectal cancer (e.g., colon cancer), gallbladder cancer, kidney cancer, or liver cancer, or neuroblastoma).

[0204] Compounds that are particularly effective inhibitors of human NMT can be suitably used in the treatment and / or prevention of hyperproliferative disorders (e.g., cancer) and viral infections (e.g., human immunodeficiency virus (HIV), human rhinovirus (RV, formerly abbreviated as HRV)), as well as other diseases for which inhibition of human NMT has been proposed as a therapeutic agent.

[0205] In one preferred embodiment, the compounds of the present invention are for use in the treatment of diseases or disorders selected from overproliferative disorders and viral infections.

[0206] (Overproliferative disorder) In one particularly preferred embodiment, the compounds of the present invention are for use in the prevention or treatment of a hyperproliferative disorder, wherein the hyperproliferative disorder is cancer. In one particularly preferred embodiment, the compounds of the present invention are for use in the prevention of a hyperproliferative disorder, wherein the hyperproliferative disorder is cancer. In one particularly preferred embodiment, the compounds of the present invention are for use in the treatment of a hyperproliferative disorder, wherein the hyperproliferative disorder is cancer. Cancer may be selected from the group consisting of colorectal cancer, gallbladder cancer, brain tumors, lymphomas (e.g., B-cell lymphoma (e.g., diffuse large B-cell lymphoma)), leukemias (e.g., acute myeloid leukemia (AML)), and neuroblastoma.

[0207] Cancer may further, or instead, be a solid tumor selected from the group consisting of brain tumors, lung cancer, breast cancer (e.g., triple-negative breast cancer or invasive breast cancer), prostate cancer, ovarian cancer, colorectal cancer (e.g., colon), gallbladder cancer, kidney cancer, and liver cancer. For example, cancer may be ovarian serous cystadenocarcinoma, esophageal cancer, lung squamous cell carcinoma, lung adenocarcinoma, bladder urothelial carcinoma, uterine carcinosarcoma, gastric adenocarcinoma, invasive breast cancer, or hepatocellular carcinoma of the liver. In some embodiments, cancer is breast cancer, e.g., triple-negative breast cancer or invasive breast cancer. In some embodiments, cancer is a brain tumor, breast cancer, prostate cancer, colon cancer, gallbladder cancer, or kidney cancer. In some embodiments, cancer is breast cancer, colon cancer, or gallbladder cancer.

[0208] Cancer may also be, or instead, hematological malignancies selected from the group consisting of lymphoma (e.g., B-cell lymphoma, in particular selected from the group consisting of high-grade mantle lymphoma, follicular lymphoma, plasmablastic lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma), myeloma (e.g., multiple myeloma), and leukemia (e.g., leukemia selected from the group consisting of chronic lymphocytic leukemia, AML, and B-acute lymphocytic leukemia).

[0209] The cancer may also be a cancer of neuronal origin (i.e., a cancer of the nervous system), and in particular, the cancer may be selected from neuroblastoma, retinoblastoma, glioblastoma, small cell lung cancer, and astrocytoma. In certain embodiments, the cancer is a blastoma, in particular neuroblastoma, retinoblastoma, or glioblastoma. In some embodiments, the cancer is neuroblastoma.

[0210] In one embodiment, cancer may be selected from the group consisting of diffuse large B-cell lymphoma, Burkitt lymphoma, multiple myeloma, neuroblastoma, AML, and B-acute lymphoblastic leukemia. In another embodiment, cancer may be selected from the group consisting of diffuse large B-cell lymphoma, Burkitt lymphoma, neuroblastoma, AML, B-acute lymphoblastic leukemia, and breast cancer. In yet another embodiment, cancer may be selected from the group consisting of diffuse large B-cell lymphoma, neuroblastoma, B-acute lymphoblastic leukemia, and triple-negative breast cancer. In yet another embodiment, cancer may be selected from the group consisting of colorectal cancer, gallbladder cancer, brain tumor, lymphoma (e.g., diffuse large B-cell lymphoma), leukemia (e.g., acute myeloid leukemia), and blastoma (e.g., neuroblastoma, retinoblastoma, or glioblastoma, preferably neuroblastoma). In another embodiment, the cancer may be selected from the group consisting of diffuse large B-cell lymphoma, Burkitt lymphoma, multiple myeloma, neuroblastoma, AML, B-acute lymphoblastic leukemia, and triple-negative breast cancer. In another embodiment, the cancer may be selected from the group consisting of multiple myeloma, neuroblastoma, AML, B-acute lymphoblastic leukemia, and triple-negative breast cancer. In another embodiment, the cancer may be selected from the group consisting of multiple myeloma, neuroblastoma, and triple-negative breast cancer.

[0211] The oncogenes c-MYC and MYCN are common diagnostic markers, particularly for invasive types of malignant tumors, and recent findings have shown a strong correlation between overexpression and / or mutations of c-MYC and MYCN and some of the worst clinical outcomes (Jung et al., Tumor and Stem Cell Biology, 2016, 65(16), 7065-7070; Habermann et al., Blood, 2016, 128(22), 155; Xu et al., Genes Cancer, 2010, 1(6), 629-640). Therefore, there is a continuing need for improved therapies that can target cancers with one or more structural alterations in the MYC oncogene.

[0212] The compounds of the present invention are particularly well suited for use in the treatment of cancers that are i) dependent on the MYC oncogene and / or ii) have one or more structural changes at the MYC oncogene locus.

[0213] Therefore, the compounds of the present invention may be used in the treatment of MYC-dependent cancer. Preferably, the compounds may be used in the prevention of MYC-dependent cancer. Preferably, the compounds of the present invention may be used in the prevention or treatment of MYC-dependent cancer. Preferably, MYC-dependent cancer is a cancer that depends on c-MYC and / or MYCN. In one embodiment, MYC-dependent cancer is a cancer that depends on c-MYC, and preferably, MYC-dependent cancer is a cancer that is transcriptionally dependent on c-MYC. In another embodiment, MYC-dependent cancer is a cancer that depends on MYCN, and preferably, MYC-dependent cancer is a cancer that is transcriptionally dependent on MYCN.

[0214] In certain embodiments, the present invention provides compounds for use in the prevention or treatment of c-MYC or MYCN-dependent cancers in which the c-MYC or MYCN oncogene is overexpressed, for example, in therapeutic use. Preferably, the present invention provides compounds for use in the prevention or treatment of c-MYC or MYCN-dependent cancers in which the c-MYC or MYCN oncogene is overexpressed such that the levels of c-MYC or MYCN RNA transcript and / or protein are at least 25% higher than the levels of c-MYC or MYCN RNA transcript and / or protein found in normal healthy cells, or pharmaceutically acceptable salts, solvates, or hydrates thereof.

[0215] More preferably, the present invention provides compounds of the present invention, or pharmaceutically acceptable salts, solvates, or hydrates thereof, for use in the prevention or treatment of c-MYC or MYCN-dependent cancers, for example, in therapeutic use, in which the levels of c-MYC or N-MYC RNA transcripts and / or proteins are overexpressed such that the levels of c-MYC or N-MYC RNA transcripts and / or proteins are at least 50% greater than the levels of c-MYC or N-MYC RNA transcripts and / or proteins observed in normal healthy cells.

[0216] The present invention also provides compounds for use in the prevention or treatment of MYC dysregulation cancers, for example, in therapeutic use. MYC dysregulation cancers may include, for example, cancers involving mutations and / or structural changes in the MYC oncogene that confer overexpression or stabilization of MYC at the protein and / or mRNA level. A non-restrictive list of possible mutations includes: i) point mutations in the MYC coding region (Bahram et al., Blood, 2000, 95, 2104-2110); ii) mutations in distal enhancers (Sur et al., Science, 2012, 338, 1360-1363 and Zhang et al., Nat. Genet., 2016, 48-176-182); and iii) activation mutations in signaling pathways that enhance MYC expression (Herranz et al., Nat. Med., 2014, 20, 1130-1137, Muncan et al., Mol. Cell Biol., 2006, 26, 8418-8426, and Weng et al., Genes Dev., 2006, 20, 2096-2109).

[0217] In one embodiment, MYC dysregulation cancer is cancer that overexpresses the MYC oncogene. Preferably, MYC dysregulation cancer is cancer that overexpresses the c-MYC or MYCN oncogene. More preferably, MYC oncogene dysregulation cancer is cancer that overexpresses the c-MYC or MYCN oncogene, wherein the c-MYC or MYCN is overexpressed such that the level of c-MYC or MYCN RNA transcript and / or protein is at least 25% higher than the level of c-MYC or MYCN RNA transcript and / or protein found in normal healthy cells. More preferably, MYC dysregulation cancer is cancer that overexpresses the c-MYC or MYCN oncogene, wherein the c-MYC or MYCN is overexpressed such that the level of c-MYC or MYCN RNA transcript and / or protein is at least 50% higher than the level of c-MYC or MYCN RNA transcript and / or protein found in normal healthy cells.

[0218] The present invention further provides compounds of the present invention for use in the prevention or treatment of cancer, for example, in therapeutic use, wherein the cancer comprises one or more structural changes in the MYC locus. Non-limiting examples of “structural changes” include, for example, mutations, copy number increases, and / or chromosomal rearrangements. In one embodiment, the present invention provides compounds of the present invention for use in the prevention or treatment of cancer, for example, in therapeutic use, wherein the cancer comprises one or more mutations in the MYC locus. Preferably, the present invention provides compounds of the present invention for use in the prevention or treatment of cancer, for example, in therapeutic use, wherein the cancer comprises one or more mutations in the MYC locus that confer overexpression of MYC. More preferably, the present invention provides compounds of the present invention for use in the prevention or treatment of cancer, for example, in therapeutic use, wherein the cancer comprises one or more mutations in the MYC locus that confer overexpression of c-MYC or MYCN. In a particular embodiment, the present invention provides compounds of the present invention for use in the prevention or treatment of cancer, for example, in therapeutic use, wherein the cancer comprises one or more mutations in c-MYC. In another specific embodiment, the present invention provides compounds for use in the prevention or treatment of cancer, for example, in the treatment of cancer comprising one or more mutations of MYCN.

[0219] In certain embodiments, compounds of the present invention are provided for use in the prevention or treatment of cancer, for example, in the treatment of cancer comprising one or more mutations in the MYC gene locus that confer stabilization of MYC.

[0220] In certain embodiments, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC gene locus is a cancer selected from hematological malignancies or solid tumors.

[0221] In another embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is a hematological malignancy. Preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is a hematological malignancy selected from lymphoma, myeloma, or leukemia.

[0222] In another embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is lymphoma. Preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is a lymphoma selected from high-grade mantle layer lymphoma, follicular lymphoma, plasmablastic lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. More preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is a lymphoma selected from diffuse large B-cell lymphoma or Burkitt lymphoma. More preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is diffuse large B-cell lymphoma.

[0223] In another embodiment, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes at the MYC locus is myeloma. Preferably, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes at the MYC locus is multiple myeloma.

[0224] In another embodiment, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes in the MYC locus is a leukemia. Preferably, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes in the MYC locus is a leukemia selected from chronic lymphocytic leukemia, acute myeloid leukemia, and B-acute lymphocytic leukemia. Most preferably, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes in the MYC locus is B-acute lymphocytic leukemia.

[0225] In another embodiment, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes at the MYC locus is a blastoma. Preferably, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes at the MYC locus is a blastoma selected from neuroblastoma, retinoblastoma, and glioblastoma. More preferably, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes at the MYC locus is a blastoma selected from retinoblastoma and glioblastoma. In a particular embodiment, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer comprising one or more structural changes at the MYC locus is a neuroblastoma.

[0226] In another embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural alterations of the MYC locus is a cancer of neuronal origin (i.e., a cancer of the nervous system). In a particular embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural alterations of the MYC locus is selected from neuroblastoma, retinoblastoma, glioblastoma, small cell lung cancer, and astrocytoma.

[0227] In another embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is a solid tumor. In one embodiment, a solid tumor is a carcinoma. Preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is a solid tumor in an organ selected from the brain, lungs, breast, prostate, ovaries, colon, gallbladder, kidneys, and liver. More preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is a solid tumor in an organ selected from the brain, breast, prostate, colon, gallbladder, and kidneys. Even more preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is a solid tumor in an organ selected from the breast, colon, and gallbladder.

[0228] In one embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is a solid tumor selected from ovarian serous cystadenocarcinoma, esophageal cancer, lung squamous cell carcinoma, lung adenocarcinoma, bladder urothelial carcinoma, uterine carcinosarcoma, gastric adenocarcinoma, invasive breast cancer, and hepatocellular carcinoma of the liver.

[0229] In one embodiment, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer involving one or more structural changes at the MYC locus is breast cancer. Preferably, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer involving one or more structural changes at the MYC locus is triple-negative breast cancer or invasive breast cancer. In a particular embodiment, a MYC-dependent cancer, a MYC-dysregulated cancer, or a cancer involving one or more structural changes at the MYC locus is basal-like breast cancer.

[0230] In another embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC gene locus is cancer of the gallbladder.

[0231] In other embodiments, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC gene locus is colorectal cancer.

[0232] In other embodiments, MYC-dependent cancer, MYC-dysregulated cancer, or cancer involving one or more structural changes in the MYC locus is a brain tumor (e.g., astrocytoma).

[0233] In one embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is selected from diffuse large B-cell lymphoma, Burkitt lymphoma, multiple myeloma, blastoma (e.g., neuroblastoma, retinoblastoma, or glioblastoma), acute myeloid leukemia, B-acute lymphoblastic leukemia, and solid tumors in organs selected from the breast, colon, and gallbladder. Preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is selected from large B-cell lymphoma, Burkitt lymphoma, neuroblastoma, retinoblastoma, glioblastoma, acute myeloid leukemia, B-acute lymphoblastic leukemia, and breast cancer. More preferably, MYC-dependent cancers, MYC-dysregulated cancers, or cancers involving one or more structural changes in the MYC locus are selected from diffuse large B-cell lymphoma, neuroblastoma, B-acute lymphoblastic leukemia, and triple-negative breast cancer.

[0234] In certain embodiments, MYC-dependent cancers, MYC-dysregulated cancers, or cancers involving one or more structural changes at the MYC locus include colorectal cancer, gallbladder cancer, brain tumors, lymphomas (e.g., diffuse large B-cell lymphoma), leukemias (e.g., acute myeloid leukemia), or blastomas (e.g., neuroblastoma, retinoblastoma, or glioblastoma).

[0235] In one embodiment, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is diffuse large B-cell lymphoma, Burkitt lymphoma, multiple myeloma, blastoma (e.g., neuroblastoma, retinoblastoma, or glioblastoma), acute myeloid leukemia, B-acute lymphoblastic leukemia, or triple-negative breast cancer. Preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is multiple myeloma, neuroblastoma, retinoblastoma, glioblastoma, acute myeloid leukemia, B-acute lymphoblastic leukemia, or triple-negative breast cancer. More preferably, MYC-dependent cancer, MYC-dysregulated cancer, or cancer comprising one or more structural changes of the MYC locus is multiple myeloma, neuroblastoma, retinoblastoma, glioblastoma, or triple-negative breast cancer. More preferably, MYC-dependent cancers, MYC-dysregulated cancers, or cancers involving one or more structural changes in the MYC gene locus are neuroblastoma or triple-negative breast cancer (e.g., basal-like breast cancer).

[0236] In certain embodiments, the present invention provides compounds of the present invention, or pharmaceutically acceptable salts, solvates, or hydrates thereof, for use in the prevention or treatment of blastoma, for example, in treatment, wherein the blastoma comprises one or more mutations of MYCN. Preferably, the blastoma is selected from neuroblastoma, retinoblastoma, and glioblastoma. Most preferably, the present invention provides compounds of the present invention, or pharmaceutically acceptable salts, solvates, or hydrates thereof, for use in the prevention or treatment of neuroblastoma, for example, in treatment, wherein the neuroblastoma comprises one or more mutations of MYCN.

[0237] In another specific embodiment, the present invention provides compounds for use in the prevention or treatment of c-MYC-dependent cancer, for example, in the treatment of, where the c-MYC-dependent cancer is breast cancer. Preferably, the present invention provides compounds for use in the prevention or treatment of c-MYC-dependent cancer, for example, in the treatment of, where the c-MYC-dependent cancer is triple-negative breast cancer (e.g., basal-like breast cancer) or invasive breast cancer.

[0238] The present invention also provides a method for the prevention or treatment of MYC-dependent cancers in subjects requiring such treatment, for example, a method for treatment comprising administering a therapeutically effective amount of the compound of the present invention. Preferably, MYC-dependent cancer is any one of the above-described MYC-dependent cancers.

[0239] Further provided are methods for the prevention or treatment of MYC dysregulation cancer in subjects requiring such treatment, for example, a method for treatment comprising administering a therapeutically effective amount of the compound of the present invention. Preferably, MYC dysregulation cancer is any one of the above-described MYC dysregulation cancers.

[0240] Further provided are methods for the prevention or treatment of cancers involving one or more structural alterations of the MYC locus in subjects requiring such treatment, for example, methods for treatment comprising administering a therapeutically effective amount of the compound of the present invention. Preferably, cancers involving one or more structural alterations of the MYC locus are any one of the cancers described above.

[0241] A further aspect of the present invention provides a method for determining whether a subject having cancer would benefit from treatment with the compound of the present invention, i) The step of taking a sample of cancer cells collected from the subject; ii) A step of analyzing the cancer cells from step i) to investigate the presence of one or more structural changes (e.g., chromosomal rearrangements, copy number increase, and / or mutations) at the MYC gene locus; iii) A step of determining whether one or more structural changes (e.g., chromosomal rearrangements, copy number increases, and / or mutations) are present in the MYC locus of the cancer cell sample when compared to a control; and iv) A step of determining whether the subject would benefit from being administered the compound of the present invention to treat the cancer (wherein if the sample of cancer cells contains one or more structural changes in the MYC locus (e.g., chromosomal rearrangement, copy number increase, and / or mutation), the subject would benefit from being administered the compound of the present invention, and if the sample of cancer cells does not contain one or more structural changes in the MYC locus (e.g., chromosomal rearrangement, copy number increase, and / or mutation), the subject would not benefit from being administered the compound of the present invention). A method including the colon (:) is provided.

[0242] In one embodiment, one or more structural changes are chromosomal rearrangements. Therefore, preferably, step ii) of the above method includes analyzing the cancer cells of step i) to investigate the presence of one or more chromosomal rearrangements at the MYC locus. Those skilled in the art will be able to readily determine a suitable technique for investigating the presence of one or more chromosomal rearrangements at the MYC locus. One non-limiting example of a suitable technique for investigating the presence of one or more chromosomal rearrangements at the MYC locus is fluorescence in situ hybridization (FISH).

[0243] In another embodiment, one or more structural changes are mutations. Therefore, preferably, step ii) of the above method includes analyzing the cancer cells of step i) to investigate the presence of one or more mutations at the MYC locus. Those skilled in the art will be able to readily determine a suitable technique for investigating the presence of one or more mutations at the MYC locus. One non-limiting example of a suitable technique for investigating the presence of one or more mutations at the MYC locus is gene sequencing.

[0244] Preferably, the control in step iii) is a structural rearrangement of the MYC locus found in normal healthy cells, and more specifically, the control in step iii) is a chromosomal rearrangement and / or gene sequence found in the MYC locus of normal healthy cells.

[0245] It will be understood that a sample of cancer cells taken from the subject can be obtained by any preferred method known in the art. For example, the sample of cancer cells taken from the subject may be taken from a biopsy, or it may be a sample of circulating tumor cells (CTCs) taken from the subject.

[0246] A further aspect of the present invention provides a method for determining whether a subject with cancer would benefit from treatment with an NMT inhibitor, i) A step of measuring the level of MYC expression in a sample of cancer cells taken from the subject; ii) A step of comparing the level of MYC expression in step i) with a control; iii) A step of determining whether MYC expression in the cancer cell sample is increased compared to the control; and iv) A step of determining whether the subject would benefit from being administered the compound of the present invention to treat the cancer (wherein if the MYC expression in the sample of cancer cells is higher than that of the control, the subject would benefit from being administered the compound of the present invention, and if the MYC expression in the sample of cancer cells is not higher than that of the control, the subject would not benefit from being administered the compound of the present invention). A method is provided that includes:

[0247] It will be understood that the level of MYC expression in a sample of cancer cells can be determined by any suitable means known in the art. For example, the level of MYC expression can be determined by measuring the MYC protein level. The MYC protein level can be measured using any suitable technique known in the art, such as SDS-PAGE followed by Western blotting using a suitable antibody prepared against the target protein. Alternatively, the level of MYC expression can be determined by measuring the mRNA level. The mRNA level can be measured using any suitable technique known in the art, such as Northern blotting or quantitative RT-PCR (qRT-PCR).

[0248] Preferably, the control in step ii) above is the MYC expression level observed in normal healthy cells, for example, normal healthy cells of the same type as the cells being investigated. It will be understood that the MYC expression level observed in normal healthy cells may also be determined using any of the techniques described in paragraph

[0091] above.

[0249] A further aspect of the present invention provides a method for the prevention or treatment of cancer in a subject identified as beneficial to the administration of the compound of the present invention as determined by the above method, for example, a method for treatment comprising administering a therapeutically effective amount of the compound of the present invention.

[0250] (Viral infections and related diseases) In another preferred embodiment, the compounds of the present invention are for use in the prevention or treatment of viral infections, and in particular enterovirus infections, retrovirus infections, or poxvirus infections, for example, in the treatment of such infections. For example, enterovirus infections may be picornavirus infections (e.g., rhinovirus, poliovirus, foot and mouth disease virus, coxsackievirus, hepatitis A virus, or enterovirus 71 infection); retrovirus infections may be lentivirus infections (e.g., HIV infection); and poxvirus infections may be orthopoxvirus, parapoxvirus, yataboxvirus, or morsipoxvirus infections. Therefore, viral infections may be selected from the group consisting of rhinovirus infection (e.g., RV, also known as the common cold), lentivirus infection (e.g., HIV infection), poliovirus infection, foot and mouth disease virus infection, coxsackievirus infection, hepatitis A virus infection, enterovirus 71 infection, smallpox virus infection, vaccinia virus infection, cowpox virus infection, monkeypox virus infection, buffalo poxvirus infection, camel poxvirus infection, ectromelia virus infection, rabbit poxvirus infection, raccoon poxvirus infection, seal poxvirus infection, skunk poxvirus infection, gerbil (tatera) poxvirus infection, wild rodent (vole) poxvirus infection, pustular dermatitis virus infection, pseudocowpox infection, bovine papular stomatitis virus infection; tanapoxvirus infection, yabasal tumor virus infection, and molluscum contagiosum virus (MCV) infection. This may preferably be selected from the group consisting of rhinovirus infection (e.g., RV, also known as the common cold), lentivirus infection (e.g., HIV infection), poliovirus infection, foot and mouth disease virus infection, coxsackievirus infection, hepatitis A virus infection, enterovirus 71 infection, poxvirus (smallpox) infection, vaccinia virus infection, cowpox virus infection, monkeypox virus infection, pustular dermatitis virus infection, pseudocowpox infection, bovine papular stomatitis virus infection; tanapoxvirus infection, yabasal tumor virus infection, and molluscum contagiosum virus (MCV) infection.In one particularly preferred embodiment, the compounds of the present invention are for use in the prevention or treatment of viral infections, for example, in the treatment of a viral infection, where the viral infection is a picornavirus infection, and more particularly, it is a rhinovirus infection (e.g., RV, also known as the common cold).

[0251] The aforementioned viral infections cause many types of diseases. For example: rhinovirus infection causes the common cold; various picornavirus infections (especially coxsackievirus and enterovirus 71) cause hand, foot, and mouth disease and polio-like syndrome; coxsackievirus also causes flaccid paralysis, herpangina, acute hemorrhagic conjunctivitis, nonspecific febrile illnesses, rashes, upper respiratory tract diseases, pericardial effusion, insulin-dependent diabetes mellitus (IDDM), Sjögren's syndrome, myocarditis (inflammation of the heart), pericarditis (inflammation of the sac surrounding the heart), meningitis (inflammation of the membranes covering the brain and spinal cord), and pancreatitis (inflammation of the pancreas); enterovirus 71 also causes severe neurological disorders in children; foot and mouth disease virus causes foot and mouth disease; hepatitis A virus causes hepatitis A; HIV infection can cause acquired immunodeficiency syndrome (AIDS); poxvirus (smallpox) infection causes smallpox; cowpox virus infection causes cowpox; monkeypox virus infection causes monkeypox; pustular dermatitis virus infection causes pustular dermatitis; pseudocowpox infection causes pseudocowpox; bovine papular stomatitis virus infection causes bovine papular stomatitis; tanapox virus infection can cause acute febrile illness and localized skin lesions; yabasal tumor virus infection can cause the formation of cutaneous histiocytoma; and molluscum contagiosum virus (MCV) infection causes molluscum contagiosum. The compounds of the present invention can be used in the prevention or treatment of the aforementioned diseases caused by the aforementioned viral infections, as well as other diseases and illnesses caused by enterovirus infections, retrovirus infections, or poxvirus infections, for example, in the treatment of these diseases.

[0252] (microbial infection) In another embodiment, the compounds of the present invention are for use in the prevention or treatment of diseases or disorders, for example, in treatment, of microbial infections; for example, fungal infections, for example, Aspergillus infections, and protozoan infections, for example, malaria, leishmaniasis, human African trypanosomiasis (sleeping sickness), and American trypanosomiasis (Chagas disease). In one embodiment, the compounds for the present invention are for use in the prevention or treatment of diseases or disorders, for example, in treatment, of diseases or disorders selected from the group consisting of aspergillosis, malaria, leishmaniasis, human African trypanosomiasis (sleeping sickness), and American trypanosomiasis (Chagas disease), in particular malaria, leishmaniasis, human African trypanosomiasis (sleeping sickness), and American trypanosomiasis (Chagas disease).

[0253] In one embodiment, the compounds of the present invention are for the prevention or treatment of diseases or disorders that are protozoal infections caused by species of the genera Plasmodium, Leishmania, or Trypanosoma (e.g., Plasmodium falciparum, Plasmodium vivax, Donovan's leishmania, Leishmania major, Trypanosoma brusii, Trypanosoma cruzi).

[0254] Compounds that are particularly good inhibitors of NMT enzymes of specific non-human species (e.g., Plasmodium falciparum, Plasmodium vivax, Donovan leishmania, Leishmania major, Trypanosoma brusii, Trypanosoma cruzi); and / or compounds of the present invention that are more selective to NMT enzymes of specific species (e.g., Plasmodium falciparum, Plasmodium vivax, Donovan leishmania, Leishmania major, Trypanosoma brusii, Trypanosoma cruzi) than to human NMT (human NMT1 and / or human NMT2) may be particularly useful in the prevention or treatment of diseases associated with these species, for example, in the treatment of diseases. For example, they may be particularly useful in the prevention or treatment of diseases or disorders selected from malaria, leishmaniasis, and sleeping sickness, for example, in the treatment of diseases.

[0255] For example, the use of selective NMT inhibitors may result in fewer side effects compared to the use of less selective compounds. In one embodiment, an NMT inhibitor is selective for non-human NMTs (e.g., Plasmodium falciparum, Plasmodium vivax, Donovan-leishmania, Trypanosoma brusii, and / or Trypanosoma cruzi) rather than human NMTs (e.g., human NMT1 and / or human NMT2). 50 Value vs. Non-human NMT IC 50 A ratio of values ​​is considered selective if it is greater than 5, preferably greater than 10, more preferably greater than 100, and most preferably greater than 1000.

[0256] (Other diseases) In another embodiment, the compounds of the present invention are for the prevention or treatment of diseases or disorders selected from the group consisting of neurological diseases / disorders, ischemia, osteoporosis, and diabetes, for example, for use in treatment. In a further embodiment, the compounds of the present invention are for the prevention or treatment of diseases or disorders selected from the group consisting of autoimmune diseases and inflammatory diseases, for example, for use in treatment.

[0257] (diagnosis) In one embodiment, the compounds of the present invention include isotopic atoms, preferably radioisotopic atoms. As defined herein, isotopic atoms are atoms of elements that are not the most common natural isotopes. Such compounds can be used as diagnostic agents for diagnosing diseases or disorders in which inhibition of NMTs results in a therapeutic or preventive effect. Accordingly, the present invention also provides the use of the compounds of the present invention, which include isotopic atoms, preferably radioisotopic atoms, as diagnostic agents for diagnosing diseases or disorders in which inhibition of NMTs results in a therapeutic or preventive effect.

[0258] (Dosage and Formulation) The amount of active ingredient required to achieve a therapeutic effect naturally varies depending on the specific compound, the route of administration, the subject being treated (including the type, species, age, weight, sex, and medical condition of the subject, as well as the subject's renal and hepatic function), and the specific disorder or disease being treated and its severity. A physician, veterinarian, or clinician with ordinary skill can easily determine and prescribe the effective amount of drug needed to prevent, combat, or halt the progression of a disease.

[0259] The oral dosage of the present invention, when used to achieve the indicated effects, is approximately 0.01 mg / kg body weight / day (mg / kg / day) to approximately 500 mg / kg / day for adults, preferably 0.01 mg / kg body weight / day (mg / kg / day) to 100 mg / kg / day, most preferably in the range of 0.05 to 50 mg / kg / day, for example, 0.05, 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg / kg / day. For oral administration, the composition is preferably provided in the form of tablets or other forms of provision, provided in individually separated units containing 0.01, 0.05, 0.1, 0.25, 0.5, 1.0, 2.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 100, 150, 200, 250, and 500 milligrams of the active ingredient for symptomatic adjustment of the dosage for patients being treated. The pharmaceutical product typically contains about 0.01 mg to about 500 mg of the active ingredient, preferably about 1 mg to about 250 mg of the active ingredient, for example, about 1 mg to about 150 mg of the active ingredient. For intravenous administration, the most preferred dose is in the range of about 0.1 to about 10 mg / kg / min during constant-rate infusion. Advantageously, the compounds of the present invention can be administered in a once-daily dose, or the total daily dose can be administered in divided doses two, three, or four times a day. Furthermore, the compounds of the present invention can be administered intranasally by topical use of a suitable intranasal vehicle, or transdermally using transdermal skin patches as is well known to those skilled in the art. Because they are administered in the form of transdermal delivery systems, the administration of the dose will naturally be continuous rather than intermittent throughout the entire drug regimen.

[0260] Although the active ingredient can be administered alone, it is preferable that it be present in a pharmaceutical formulation or composition. Therefore, the present invention provides a pharmaceutical formulation or composition comprising the compound of the present invention and a pharmaceutically acceptable diluent, excipient, or carrier (collectively referred to herein as "carrier" material). The pharmaceutical composition of the present invention may take the following forms of pharmaceutical formulations.

[0261] Pharmaceutical formulations according to the present invention include those suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous [bolus or infusion], and intra-articular), intranasal (also known as nasal administration), inhalation (including various types of pressurized metered-dose aerosols, nebulizers, or inhalers that can generate fine particles or mist), blown, rectal, intraperitoneal, and topical (including cutaneous, buccal, sublingual, and intraocular) administration, but the most preferred route may depend, for example, on the recipient's disease and disorder.

[0262] In some embodiments, the compounds of the present invention are administered intranasally, by inhalation (including particulate powder or mist that can be generated by various types of pressurized metered-dose aerosols, nebulizers, or inhalers), or by blown-in. Such embodiments are particularly suitable for the treatment of picornavirus infections, such as human rhinovirus infection. Such administration methods allow for the administration of low doses of the compounds of the present invention, which may lead to a reduction in side effects. For example, daily doses of the compounds of the present invention may be used in amounts as low as 10 to 0.01 μg, preferably 1 to 0.01 μg, and more preferably as low as approximately 0.1 μg (100 ng).

[0263] The formulations may be conveniently provided in unit dosage forms and may be prepared by any of the methods well known in the pharmaceutical art. All methods involve associating the active ingredient with a carrier constituting one or more minor components. Generally, formulations are prepared by homogeneously and closely associating the active ingredient with a liquid carrier, a pulverized solid carrier, or both, and then, if necessary, shaping the product into the desired formulation.

[0264] Formulations of the present invention suitable for oral administration may be provided as separate units such as capsules, cachets, pills, or tablets, each containing a predetermined amount of the active ingredient; as powders or granules; as liquids or suspensions in aqueous or non-aqueous liquids, for example, as elixirs, tinctures, suspensions, or syrups; or as oil-in-water or water-in-oil emulsions. The active ingredient may also be provided as a bolus, lick, or paste.

[0265] Tablets may be prepared by compression or molding with the use of one or more auxiliary components as desired. Compressed tablets may be prepared by compressing a free-flowing active ingredient, such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, lubricant, surfactant, or dispersant, in a suitable machine. Moulded tablets may be prepared by molding a mixture of powder compounds moistened with an inert liquid diluent in a suitable machine. Tablets may optionally be coated or scored, and may be formulated to provide slow or controlled release of the active ingredient therein. The compounds of the present invention can be administered, for example, in a form suitable for immediate release or sustained release. Immediate or sustained release can be achieved by using a suitable pharmaceutical composition containing the compounds of the present invention, or, in particular for sustained release, by using a device such as a subcutaneous implant or osmotic pump. The compounds of the present invention may also be administered by liposomes.

[0266] Examples of compositions for oral administration include suspending agents that may contain, for example, microcrystalline cellulose for bulkiness, alginic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer, and sweeteners or flavoring agents such as those known in the art; and immediate-release tablets that may contain, for example, microcrystalline cellulose, dicalcium phosphate, starch, magnesium stearate, calcium sulfate, sorbitol, glucose, and / or lactose, and / or other excipients, binders, fillers, disintegrants, diluents, and lubricants such as those known in the art. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn syrup, natural and synthetic gums such as gum arabic, tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, and wax. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, and xanthan gum. The compounds of the present invention can also be delivered orally by sublingual and / or buccal administration. Wet tablets, compressed tablets, or freeze-dried tablets are exemplary forms that may be used. Exemplary compositions include formulations of the compounds with fast-dissolving diluents such as mannitol, lactose, sucrose, and / or cyclodextrin. Such formulations may also contain high molecular weight excipients such as cellulose (avicel) or polyethylene glycol (PEG). Such formulations may also contain excipients that aid adhesion to mucous membranes, such as hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (SCMC), maleic anhydride copolymer (e.g., Gantrez), and agents that control release, such as polyacrylic acid copolymer (e.g., Carbopol 934). Lubricants, flow enhancers, fragrances, colorants, and stabilizers may also be added for ease of manufacture and use. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, and sodium chloride.When administered orally in liquid form, the oral drug component can be combined with any orally non-toxic, pharmaceutically acceptable inert carrier, such as ethanol, glycerol, or water.

[0267] The compounds of the present invention can also be administered in the form of liposome delivery systems such as small monolayer vesicles, large monolayer vesicles, and multilayer vesicles. The liposomes can be formed from various phospholipids, 1,2-dipalmitoylphosphatidylcholine, phosphatidylethanolamine (cephalin), or phosphatidylcholine (lecithin).

[0268] Preparations for parenteral administration include aqueous and non-aqueous sterile injection solutions that may contain antioxidants, buffers, bacteriostatic agents, and solutes that make the preparation isotonic with the blood of the recipient to whom the preparation is intended; and aqueous and non-aqueous sterile suspensions that may contain suspending agents and thickeners. Preparations may be supplied in unit-dose or multi-dose containers, such as sealed ampoules and vials, and may be stored in a freeze-dried state requiring only the addition of a sterile liquid carrier, such as physiological saline or sterile water for injection, immediately before use. On-demand prepared injection solutions and suspensions may be prepared from the sterile powders, granules, and tablets of the types described above. Exemplary compositions for parenteral administration include injection solutions or suspensions that may contain, for example, mannitol, 1,3-butanediol, water, Ringer's solution, isotonic sodium chloride solution, or other suitable dispersants or wetting agents and suspending agents, including synthetic monoglycerides or diglycerides, as well as fatty acids containing oleic acid, or cremaphores.

[0269] Examples of compositions for intranasal, aerosol, or inhalation administration include solutions in physiological saline that may contain, for example, benzyl alcohol or other suitable preservatives, absorption enhancers to enhance bioavailability, and / or other solubilizers or dispersants known in the art.

[0270] Formulations for rectal administration may be provided as suppositories using conventional carriers such as cocoa butter, synthetic glyceride esters, or polyethylene glycol. Such carriers are usually solid at room temperature but liquefy and / or dissolve in the rectal lumen to release the drug.

[0271] Formulations for topical administration in the mouth, for example, buccally or sublingually, include lozenges containing the active ingredient in a flavored base such as sucrose and gum arabic or tragacanth, and flavored tablets containing the active ingredient in a base such as gelatin and glycerin or sucrose and gum arabic. Exemplary compositions for topical administration include topical carriers such as Plastibase (mineral oil gelled with polyethylene).

[0272] A preferred unit-dose formulation contains an effective dose of the active ingredient listed above, or a suitable portion thereof.

[0273] In addition to the components specifically mentioned above, it should be understood that the formulations of the present invention may contain other agents commonly used in the art, taking into account the type of formulation, such as fragrances, which may be suitable for oral administration.

[0274] The compounds of the present invention may be used as the sole active ingredient in a pharmaceutical, but they may also be used in combination with one or more further therapeutic agents. Accordingly, the present invention also provides the compounds of the present invention together with further therapeutic agents. The further therapeutic agents may be for simultaneous, sequential, or individual administration. The present invention also provides a kit of parts comprising: (a) a first pharmaceutical composition comprising the compounds of the present invention and a pharmaceutically acceptable carrier; and (b) a second pharmaceutical composition comprising a further therapeutic agent and a pharmaceutically acceptable carrier.

[0275] Such further therapeutic agents may be further NMT inhibitors, for example, further compounds according to the present invention (i.e., further compounds of formula (I) (or (Ia) to (Ip)), or pharmaceutically acceptable esters, amides, or carbamates thereof, or salts comprising salts of such esters, amides, or carbamates).

[0276] The compounds of the present invention can be used in combination with one or more further therapeutic agents useful for the treatment or prevention of diseases or disorders in which inhibition of N-myristoyltransferase provides a therapeutic or preventive effect (e.g., agents useful for the treatment or prevention of hyperproliferative disorders, viral infections, microbial infections, neurological diseases, ischemia, osteoporosis, diabetes, autoimmune diseases, and inflammatory diseases, in particular agents useful for the treatment or prevention of hyperproliferative disorders (e.g., cancer) and viral infections (e.g., RV or HIV infection)). The individual components of such combinations can be administered separately, in divided or single combined form at different points in time during the course of treatment. Therefore, the present invention should be understood to encompass all such arrangements of simultaneous or alternating treatment, and the term “administer” should be interpreted accordingly. The range of combinations of the compounds of the present invention with other therapeutic agents useful for the treatment or prevention of diseases or disorders in which inhibition of N-myristoyltransferase provides a therapeutic or preventive effect includes, in principle, any combination with any pharmaceutical composition useful for the treatment or prevention of diseases or disorders in which inhibition of N-myristoyltransferase provides a therapeutic or preventive effect.

[0277] Further therapeutic agents, when used in combination with the compounds of the present invention, may be used, for example, in amounts indicated in the Physician's Desk Reference (PDR) for the agent, or in amounts determined otherwise by those skilled in the art.

[0278] When the compounds of the present invention are used in combination with one or more further therapeutic agents, either simultaneously or sequentially, the following combination ratios and dosage ranges are preferred: When combined with further therapeutic agents, the compounds of the present invention may be used, for example, in a weight ratio of about 10:1 to about 1:10 relative to the further therapeutic agents.

[0279] In one embodiment, if the compound of the present invention is for the treatment or prevention of cancer, the compound of the present invention may be used for the treatment of cancer in combination with one or more further therapeutic agents, either concurrently or sequentially.

[0280] In one embodiment, if the compound of the present invention is for the treatment or prevention of RV (also known as the common cold), the compound of the present invention may be used in combination with one or more further therapeutic agents, either concurrently or sequentially, for the treatment of RV and / or for the treatment of asthma and / or for the treatment of chronic obstructive pulmonary disease (COPD).

[0281] In one embodiment, for example, if the compound of the present invention is for the treatment or prevention of microbial infections, particularly protozoan infections, the compound of the present invention is administered in combination with an effective amount of further antiprotozoal agents, such as (i) antimalarial agents; and / or (ii) anti-leishmaniasis agents; and / or (iii) anti-human African trypanosomiasis or anti-American trypanosomiasis agents. One or more of these further antiprotozoal agents may be used in combination with the compound of the present invention.

[0282] The present invention also provides a kit of parts comprising: (a) a first pharmaceutical composition comprising the compound of the present invention and a pharmaceutically acceptable carrier; and (b) a second pharmaceutical composition comprising a further therapeutic agent, preferably a further N-myristoyltransferase inhibitor and a pharmaceutically acceptable carrier.

[0283] (Synthesis of the compound of the present invention) Many synthetic routes for the compounds of the present invention can be devised by those skilled in the art, and the synthetic routes exemplified below are not limiting to the present invention. Many methods exist in the literature on heterocyclic synthesis, e.g., Joule, JA; Mills, K.: "Heterocyclic Chemistry", 2010, 5th edition, Pub. Wiley. Several possible synthetic routes are exemplified below. Where appropriate, any initially produced compound according to the present invention can be converted to another compound according to the present invention by known methods.

[0284] (A common synthesis scheme) The following synthesis scheme details the compounds of the present invention and the synthesis routes to intermediates in the synthesis of such compounds. In the following scheme, the reactive groups can be protected and deprotected with protecting groups according to established techniques well known to those skilled in the art.

[0285] The compounds can be prepared by the general methods outlined below. In the following description, unless otherwise specified, the group R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , R 8 , R 9 , R 12 , R 13 , X 1 , X 2 References to all groups, including m, p, r, n1, n2, and Z, have the same meaning as previously defined for the compound of formula (I).

[0286] (Scheme 1) [ka] Compound of formula (I) (wherein R 12 is C 1-6The alkyl compound can be prepared by reductive amination. In such cases, another compound of formula (I) (wherein R) can be prepared. 12 The hydrogen (as shown above) is reacted with an aldehyde such as formaldehyde in the presence of a reducing agent, for example, NaCNBH3.

[0287] (Scheme 2) [ka] Compound of formula (I) (wherein R 12 The compound of formula (II) (wherein Q is a nitrogen protecting group such as tert-butyloxycarbonyl (BOC)) can be prepared by reacting it with an acid such as trifluoroacetic acid.

[0288] (Scheme 3) [ka] The compound of formula (II) can be obtained by reacting the compound of formula (V) (wherein D is a halo such as chloro) with the compound of formula (IV) (wherein Q is a nitrogen protecting group such as tert-butyloxycarbonyl (BOC)) in the presence of an alcohol such as n-BuOH under microwave irradiation.

[0289] Alternatively, the compounds of formulas (V) and (IV) can be reacted under transition metal catalytic conditions using a palladium catalyst such as palladium(0)bis(dibenzylideneacetone) or (Pd2(dba)3), a ligand such as SPhos(2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl), and a base such as cesium carbonate.

[0290] (Scheme 4) [ka] The compound of formula (V) can be prepared by reacting the compound of formula (VI) with the compound of formula (VII) in the presence of a base, such as triethylamine, and a coupling agent, such as propylphosphonic anhydride.

[0291] (Scheme 5) [ka] The compound of formula (VII) can be prepared by reacting the compound of formula (VIII) with the compound of formula (IX) (wherein D and E are each independently halos such as chloroform).

[0292] (Scheme 6) [ka] Compound of formula (I) (wherein R 12 (where is H) Alternatively, the compound of formula (X) can be converted into the compound of formula (XI) (where T is C such as methyl). 1-6 It can be obtained by reacting an alkyl group (wherein Q is a nitrogen protecting group such as tert-butyloxycarbonyl (BOC)) with a base such as triethylamine. Compound of formula (I) (wherein R 12 is C 1-6 The alkyl group can be obtained using the reduction amidation method described herein.

[0293] (Scheme 7) [ka] The compound of formula (XI) is the compound of formula (XII) (wherein T is a C such as methyl). 1-6 A compound (which is alkyl) can be obtained by reacting it under oxidizing conditions using an oxidizing agent such as meta-chloroperoxybenzoic acid (m-CPBA). The compound of formula (XII) is the compound of formula (XIII) (wherein D is a halo such as chloro, and T is a C such as methyl). 1-6(It is an alkyl compound) of formula (IV) (wherein Q is tert-butyloxycarbonyl (BOC) nitrogen protecting groups such as It can be obtained by reacting with ( ) in the presence of an alcohol such as n-BuOH under microwave irradiation. Compound of formula (XIII) (wherein D is a halo such as chloro and T is a C such as methyl) 1-6 Alkyl compounds can be prepared by reacting a compound of formula (XIV) (wherein D and E are each independently halos such as chloro) with a thioling agent such as sodium thiomethoxide.

[0294] (Scheme 8) [ka] The compound of formula (X) can be obtained by reacting the compound of formula (XV) (wherein Q is a nitrogen protecting group such as tert-butyloxycarbonyl (BOC)) with an acid such as trifluoroacetic acid. The compound of formula (XV) can be obtained by reacting the compound of formula (XVI) with the compound of formula (XVII) in the presence of a base such as triethylamine and a coupling agent such as propylphosphonic anhydride.

[0295] Z [ka] The compound can be prepared, for example, using a method similar to the one described above:

[0296] (Scheme 9) [ka] Compound (II') can be prepared by reacting compound (V') and compound (IV') under the conditions described herein, for example, under the conditions of Scheme 3. By manipulating the functional group in Z, compound (I) can be provided using conditions and methods known to those skilled in the art or as described below.

[0297] (Scheme 10) [ka] The compound of formula (I) can be obtained by reacting the compound of formula (X) with the compound of formula (XI') under the conditions described herein, for example, under the conditions of scheme 6.

[0298] (Scheme 11) [ka] The compound of formula (XI') is the compound of formula (XII') (wherein T is a C such as methyl). 1-6 A compound (which is alkyl) can be obtained by reacting it under oxidizing conditions using an oxidizing agent such as meta-chloroperoxybenzoic acid (m-CPBA). The compound of formula (XII') is the compound of formula (XIII) (wherein D is a halo such as chloro, and T is a C such as methyl). 1-6 The alkyl compound can be obtained by reacting the compound of formula (IV') with an alcohol such as n-BuOH under microwave irradiation. The compound of formula (XIII) can be obtained using the methods described herein, for example, the method of scheme 7.

[0299] (The process of the present invention) Further aspects of the present invention provide a process for preparing a compound of formula (I), or an ester, amide, carbamate, or salt thereof, for example, a pharmaceutically acceptable ester, amide, carbamate, or salt of such ester, amide, or carbamate (for example, a pharmaceutically acceptable salt), and a process for preparing an intermediate or a salt thereof in the synthesis of a compound of formula (I).

[0300] The process of the present invention is described above and includes any individual steps of a multi-step scheme.

[0301] (Intermediate product of the present invention) The present invention also provides novel intermediates used in the synthesis of compounds of formula (I), for example, compounds of formulas (II) to (XVI). The specific intermediates in question have the following general formula (wherein the variable group and preference are as previously defined for compounds of formula (I) or as defined above):

[0302] Therefore, in one embodiment, - Compound of formula (II) [ka] (In the formula, R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , m, p, r, n1, n2, and R 13 Q is as defined for the compound of formula (I), and Q is as defined above. - Compound of formula (V) [ka] (In the formula, D is a halo such as chloroform, and R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 p, n1, and n2 are as defined for the compound of formula (I); - Compound of formula (VII) [ka] (In the formula, D is a halo such as chloroform, and R 6 , R 7 , R 8 , R 9 , p, X 1 n1 and n2 are as defined for the compound of formula (I); - Compound of formula (X) [ka] (In the formula, R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , p, X 2 n1 and n2 are as defined for the compound of formula (I). - Compound of formula (XI) [ka] (In the formula, Q is a nitrogen protecting group such as tert-butyloxycarbonyl (BOC), and T is a C such as methyl.) 1-6 It is alkyl, R 8 , R 9 , R 13 , X 1 , r, and m are as defined for the compound of formula (I); and - Compound of formula (XII) [ka] (In the formula, Q is a nitrogen protecting group such as tert-butyloxycarbonyl (BOC), and T is a C such as methyl.) 1-6 It is alkyl and R 8 , R 9 , R 13 , X 1 (R, m, and r are defined as they are for the compound of formula (I)) A compound selected from the group consisting of : is provided.

[0303] The present invention also provides salts, such as pharmaceutically acceptable salts, of such intermediates. [Examples]

[0304] (Examples) The following compounds are examples of compounds of the present invention, or, where appropriate, compounds for use in the present invention.

[0305] (Hplc) The purity of one example was determined by analytical HPLC using an Eclipse Extend or XDB 5μm C18 (150×4.6mm), Xbridge 5μm C18 (100×4.6mm), Zorbax Extend 5μm C18 (150×4.6mm), or Shimadzu L Column 2 ODS 5μm C18 (150×4.6mm) column, using gradient elution of acetonitrile in water containing 10mM ammonium acetate over 15 minutes (HPLC B), 17 minutes (B1), or 21 minutes (B2). The purity of one example was determined by analytical HPLC using a Poroshell 120 2.7 μm EC18 (100 × 4.6 mm), Luna Omega Polar 3 μm C18 (100 × 4.6 mm), Xbridge 5 μm C18 (150 × 4.6 mm), or Sunfire 5 μm C18 (100 × 4.6 mm) column, using gradient elution of acetonitrile in water containing 0.05% formic acid over 12 minutes (HPLC A), 14 minutes (A1), or 17 minutes (A2). The purity of another example was determined by analytical HPLC using a Gemini NX 3 μm C18 (100 × 4.6 mm) column, using gradient elution of acetonitrile in water containing 0.05% formic acid over 12 minutes (A3). The HPLC methods used in each example are shown below.

[0306] (NMR) 1 H and 13Unless otherwise specified, 13C NMR spectra were recorded at room temperature using 400 MHz and 101 MHz Bruker AV instruments, respectively, and referenced to the residual solvent signal. The data are presented as follows: chemical shift in ppm, integral, multiplicity (br=broad, app=apparent, s=singular, d=double, t=tripular, q=quadular, p=quintular, m=multiplex), and coupling constants in Hz.

[0307] (Preparative HPLC) Preparative HPLC was performed using a Waters automated HPLC system. Column name: YMC Triart Actus C18 (250 × 20 mm, 5 μm) operating at ambient temperature and a flow rate of 16 mL / min. Mobile phase: A = 20 mM ammonium bicarbonate in water, B = acetonitrile; gradient profile: initial mobile phase composition of 80% A and 20% B, then 70% A and 30% B after 3 minutes, then 20% A and 80% B after 20 minutes, then 5% A and 95% B after 21 minutes, held in this composition for 23 minutes for column washing, then returned to the initial composition at 24 minutes and held for 26 minutes.

[0308] (preparative TLC) Preparative TLC is prepared using 60g of TLC silica gel. 254 The experiment was conducted using a 20 x 20 cm glass plate (Merck).

[0309] (Microwave) All microwave reactions were carried out using a CEM Discover (model number 908010) microwave reactor.

[0310] (General procedure) (Boc deprotection) A DCM-stirred solution of Boc-protected amine was treated with TFA (trifluoroacetic acid). The reaction mixture was stirred at room temperature for 4 hours. All volatile substances were removed under reduced pressure, and the product was purified by LC-MS or preparative TLC.

[0311] (Reduction and Amination) A stirred solution of secondary amine in MeOH was treated with aqueous formaldehyde solution (5 mol equivalents), and the mixture was stirred at room temperature (RT) for 1 hour. Sodium cyanoborohydride NaCNBH3 (3 mol equivalents) was added at 0°C, and the reaction mixture was stirred at RT for 16 hours. The reaction mixture was quenched with NaHCO3 solution and extracted by DCM. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by preparative TLC or LC-MS.

[0312] (Diamine substitution (Method A)) A solution of 2-chloropyrimidine and diamine (3 mol equivalents) in n-butanol was treated with triethylamine (6 mol equivalents), and then heated at 160°C for 160 minutes under microwave irradiation. The reaction mixture was evaporated under reduced pressure, and the crude product was purified by LC-MS or preparative TLC.

[0313] (Diamine substitution (Method B)) A DME solution containing 2-chloropyridine or 2-chloropyrimidine, diamine (3 mol equivalents), and cesium carbonate (5 mol equivalents) was purged with argon for 10 minutes, after which a catalytic amount of Pd2(dba)3 (0.05 equivalents) and either 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhOs) or 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (1.2 equivalents) was added. After further purging with argon for 5 minutes, the mixture was heated at 120°C overnight. The reaction mixture was extracted with ethyl acetate, washed with water and brine, dried over Na2SO4, and evaporated under vacuum. The crude product was then purified by column chromatography, LC-MS, or preparative TLC.

[0314] (Intermediate 1) [ka] (1-(2,5-dichloropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) (Process 1) Azetidine-3-carboxylic acid (3.31 g, 32.8 mmol) was added to a stirred solution of 2,4,5-trichloropyrimidine (6.0 g, 32.8 mmol) in a mixture of EtOH (20 mL) and water (50 mL), and the mixture was heated under reflux for 5 hours. The reaction mixture was cooled to RT, filtered, and the solid was recovered. When the solid was azeotropically reacted with toluene, 1-(2,5-dichloropyrimidine-4-yl)azetidine-3-carboxylic acid (3.5 g, 43%) was obtained as a white solid. [ka] LCMS m / z 248

[0315] (Process 2) Et3N (7.87 mL, 56 mmol) was added to a solution of 1-(2,5-dichloropyrimidine-4-yl)azetidine-3-carboxylic acid (3.5 g, 14.1 mmol) and 2-{imidazo[1,2-a]pyridine-3-yl}propan-2-amine (2.47 g, 14.1 mmol) in THF (40 mL). Propylphosphonic anhydride (T3P®, 50%, 12.4 mL, 42 mmol) was added, and the reaction mixture was stirred in RT for 2 days. The reaction mixture was quenched with NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water, dried over Na2SO4, and concentrated under reduced pressure to obtain the desired product, 1-(2,5-dichloropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide (4.0 g, 70%). [ka] LCMS m / z 405

[0316] (Intermediate 2) (1-(2-chloro-5-fluoropyridine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) (Process 1) (Methyl 1-(2-chloro-5-fluoropyridine-4-yl)azetidine-3-carboxylate) A 5 mL solution of dioxane containing 2-chloro-5-fluoro-4-iodopyridine (300 mg, 1.16 mmol), methylazetidine-3-carboxylate trifluoroacetic acid (TFA) salt (267 mg, 1.16 mmol), and cesium carbonate (1.1 g, 3.5 mmol) was purged with argon for 10 minutes, after which Pd2(OAc)2 (10.4 mg, 0.047 mmol) and XanthphOs (40.5 mg, 0.07 mmol) were added. After further purging with argon for 5 minutes, the mixture was heated at 110°C for 16 hours. The reaction mixture was extracted with ethyl acetate, washed with water and brine, dried over Na2SO4, and evaporated under vacuum. Subsequently, the crude product was purified by combiflush chromatography by elution with 3% MeOH in DCM, yielding methyl 1-(2-chloro-5-fluoropyridine-4-yl)azetidine-3-carboxylate (150 mg, 53%). LCMS MH + 245.

[0317] (Process 2) (1-(2-chloro-5-fluoropyridine-4-yl)azetidine-3-carboxylic acid) A solution of methyl 1-(2-chloro-5-fluoropyrimidine-4-yl)azetidine-3-carboxylate (300 mg, 1.22 mmol) in THF-methanol (10:1, 8.8 mL) was treated with lithium hydroxide (128 mg, 3.1 mmol) in water (1.5 mL). The resulting mixture was stirred at RT for 3 hours. The reaction mixture was cooled to 0°C, acidified with saturated citric acid solution, and extracted with 5% MeOH in DCM. The organic layer was dried over sodium sulfate and concentrated to obtain 1-(2-chloro-5-fluoropyrimidine-4-yl)-3-methylazetidine-3-carboxylic acid (200 mg, 70%). [ka]

[0318] (Step 3) (1-(2-chloro-5-fluoropyridine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) Et3N (0.725 mL, 5.2 mmol) was added to a solution of 1-(2-chloro-5-fluoropyridine-4-yl)azetidine-3-carboxylic acid (300 mg, 1.3 mmol) and 2-{imidazo[1,2-a]pyridine-3-yl}propan-2-amine (228 mg, 1.3 mmol) in THF (80 mL). T3P® (50%, 1.1 mL, 3.9 mmol) was added, and the mixture was stirred at RT for 1 day. The reaction mixture was quenched with NaHCO3 solution and extracted with Â. The organic layer was washed with water, dried on Na2SO4, concentrated under reduced pressure, and purified by column chromatography by elution with 2% MeOH in DCM to obtain 1-(2-chloro-5-fluoropyridine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide (150 mg, 30%). [ka] LCMS m / z 388

[0319] (Intermediate 3-31) All 2-chloropyrimidine intermediates were prepared from suitable 2,4-dichloropyrimidines, amino acids, and {imidazo[1,2-a]pyridine-3-yl}methaneamine using the same two-step method as described above for intermediate 1. Table 1 [Table 2] TIFF0007843754000091.tif232170TIFF0007843754000092.tif242170TIFF0007843754000093.tif222170TIFF0007843754000094.tif150170

[0320] Intermediate 20 was prepared using the same conditions as in step 2 of intermediate 1.

[0321] 1-(2-chloro-5-fluoropyrimidine-4-yl)-3-methylazetidine-3-carboxylic acid was prepared by the following route.

[0322] (Process 1) (Methyl 1-(2-chloro-5-fluoropyrimidine-4-yl)-3-methylazetidine-3-carboxylate) A stirred solution of methyl 3-methylazetidine carboxylate (491 mg, 3.0 mmol) in isopropyl alcohol (IPA, 7 mL) was treated with triethylamine (1.25 mL, 9 mmol) and 2,4-dichloro-5-fluoropyrimidine (500 mg, 3 mmol). The reaction mixture was refluxed overnight, then concentrated under reduced pressure and partitioned between ethyl acetate and aqueous NaHCO3. The organic layer was concentrated under reduced pressure and purified by column chromatography by elution with 30% EtOAC-hexane to obtain methyl 1-(2-chloro-5-fluoropyrimidine-4-yl)-3-methylazetidine-3-carboxylate (300 mg, 39%) as a colorless, rubbery substance. [ka]

[0323] (Process 2) (1-(2-chloro-5-fluoropyrimidine-4-yl)-3-methylazetidine-3-carboxylic acid) A solution of 1-(2-chloro-5-fluoropyrimidine-4-yl)-3-methylazetidine-3-carboxylate (300 mg, 1.16 mmol) in THF-water (4:1, 15 mL) was cooled to 0°C and treated with methanol (0.02 mL) and lithium hydroxide (121 mg, 2.9 mmol). The resulting mixture was stirred at RT for 3 hours. The reaction mixture was cooled to 0°C, acidified with saturated citric acid solution, and extracted with DCM. The organic layer was dried over sodium sulfate and concentrated to obtain 1-(2-chloro-5-fluoropyrimidine-4-yl)-3-methylazetidine-3-carboxylic acid (280 mg, 98%) as a colorless solid. [ka]

[0324] (Intermediate 24) (Process 1) (tert-butyl(3R)-3-[(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)carbamoyl]pyrrolidine-1-carboxylate) (R)-1-(t-butoxycarbonyl)pyrrolidine-3-carboxylic acid (300 mg, 1.67 mmol) and 2-{imidazo[1,2-a]pyridine-3-yl}propan-2-amine (293 mg, 1.67 mmol) were dissolved in THF (6 mL), treated with triethylamine (0.93 mL, 6.69 mmol), and then with T3P® (50% solution, 1.46 mL, 5.0 mmol). The mixture was stirred overnight at room temperature, then quenched with NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water, dried over Na2SO4, and concentrated under reduced pressure to obtain tert-butyl(3R)-3-[(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)carbamoyl]pyrrolidine-1-carboxylate (120 mg, 19%). [ka]

[0325] (Process 2) ((3R)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide TFA salt) tert-butyl(3R)-3-[(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)carbamoyl]pyrrolidine-1-carboxylate (200 mg, 0.54 mmol) was dissolved in DCM (5 mL) and treated with TFA (0.4 mL). The mixture was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product ((3R)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide TFA salt, 207 mg) was used without purification.

[0326] (Step 3) ((3R)-1-(2,5-dichloropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide) The crude product from step 2 was dissolved in isopropanol (6 mL) and treated with 2,4,5-trichloropyrimidine (150 mg, 0.8 mmol), followed by triethylamine (0.23 mL, 1.64 mmol). The reaction mixture was heated at 100 °C for 16 hours, concentrated, extracted with ethylethanol, and washed with brine. The crude product was purified by column chromatography on silica 5% ethylethanol-hexane to obtain the desired product (3R)-1-(2,5-dichloropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide (125 mg, 36%). [ka]

[0327] Intermediate 23 was prepared from (S)-1-(t-butoxycarbonyl)pyrrolidine-3-carboxylic acid using the same pathway as intermediate 24.

[0328] Intermediate 27 (1-(2-chloro-5-fluoropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide) was prepared from intermediate 7. [Table 3]

[0329] A THF / DME (1:1, 6 mL) solution of (1-(2-chloro-5-fluoropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-azetidine-3-carboxamide) (intermediate 7, 350 mg, 0.9 mmol) was cooled to 0°C and treated with sodium hydride (60%, 55 mg, 1.35 mmol). The mixture was maintained at 0°C for 30 minutes, then treated with iodomethane (0.067 mL, 1.08 mmol) and stirred for a further 1 hour. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic extract was washed with brine, dried on Na2SO4, and concentrated under reduced pressure to obtain (1-(2-chloro-5-fluoropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide) (240 mg, 66%). [ka]

[0330] Intermediate 28 was prepared from intermediate 1 using the same route as intermediate 27.

[0331] Intermediate 29 was prepared from 2,5-dichloro-4-iodopyridine using the same pathway as intermediate 2. [Table 4]

[0332] (Preparation of components) All components, with the exception of the following component compounds, were obtained from commercially available sources or by methods described in the literature:

[0333] (2-{imidazo[1,2-a]pyridine-3-yl}propan-2-amine) (Process 1) A mixture of 2-aminopyridine (11 g, 117 mmol) in DMF dimethylacetal (23.3 mL, 175 mmol) was stirred at 100°C for 16 hours. The reaction mixture was evaporated, the crude compound was dissolved in EtOH (60 mL), and treated with chloroacetone (10.6 mL, 132 mmol). The reaction mixture was stirred at RT for 16 hours. The reaction mixture was quenched with saturated NaHCO3 solution, extracted with ethyl acetate, washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (100-200 mesh silica, 1% MeOH-DCM) to obtain 1-{imidazo[1,2-a]pyridine-3-yl}ethane-1-one (9.0 g, 48%). [ka]

[0334] (Process 2) To a stirred solution of 1-{imidazo[1,2-a]pyridine-3-yl}ethane-1-one (7.0 g, 43.7 mmol) in THF (250 mL), MeMgBr (3 M in ether, 30 mL, 90 mmol) was added at -20°C, and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was quenched with NH4Cl solution and extracted with siRNA. The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by passing it through a column (silica gel, 100-200 mesh, 2.5% MeOH-DCM) to obtain 2-{imidazo[1,2-a]pyridine-3-yl}propan-2-ol (6.0 g, 78%). [ka] LCMS m / z 177

[0335] (Step 3) To a solution of 2-{imidazo[1,2-a]pyridine-3-yl}propan-2-ol (6.0 g, 34 mmol) in TFA (90 mL), sodium azide (11.07 g, 170 mmol) was added at 0°C, and the reaction mixture was stirred at RT for 16 hours. The reaction mixture was basicized with K2CO3 solution and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to obtain 3-(2-azidopropan-2-yl)imidazo[1,2-a]pyridine (5.3 g, 77%). [ka] LCMS m / z 191

[0336] (Step 4) A solution of 3-(2-azidopropan-2-yl)imidazo[1,2-a]pyridine (5.5 g, 27.3 mmol) in MeOH (110 mL) was degassed with argon for 15 minutes. Then, Pd-C (200 mg) was added, and the reaction mixture was stirred under an H2 balloon for 30 minutes. The reaction mixture was filtered through Celite®, and the filtrate was concentrated under reduced pressure to obtain 2-{imidazo[1,2-a]pyridine-3-yl}propan-2-amine (4.75 g, 99%). [ka] LCMS m / z 176

[0337] 2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-amine and 2-{8-fluoroimidazo[1,2-a]pyridine-3-yl}propan-2-amine were prepared from (5-methylpyridine-2-yl)amine and (3-fluoropyridine-2-yl)amine, respectively, by the same four-step method used to prepare 2-{imidazo[1,2-a]pyridine-3-yl}propan-2-amine.

[0338] (Preparation of Examples 1-112) (Example 1) [ka] (1-{5-chloro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) (Process 1) A stirring solution of 1-(2,5-dichloropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide (intermediate 1, 60 mg, 0.148 mmol) and ((R)-1-N-Boc-2-methylpiperazine (148 mg, 0.74 mmol)) in n-BuOH (0.8 mL) was heated under microwave irradiation at 120°C for 30 minutes. The reaction mixture was then RT The solution was cooled and concentrated under reduced pressure. The crude product was then purified by preparative TLC (3% MeOH in Â) to obtain tert-butyl(2R)-4-(5-chloro-4-{3-[(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)carbamoyl]azetidine-1-yl}pyrimidine-2-yl)-2-methylpiperazine-1-carboxylate as a white solid (42 mg, 50%). LCMS MH + 569.

[0339] (Process 2) A stirred solution of tert-butyl(2R)-4-(5-chloro-4-{3-[(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)carbamoyl]azetidine-1-yl}pyrimidine-2-yl)-2-methylpiperazine-1-carboxylate (42 mg, 0.074 mmol) in DCM (1 mL) was treated with TFA (0.057 mL, 0.74 mmol). The reaction mixture was stirred at room temperature for 4 hours. The crude product was dissolved in MeOH and packed into an Isolute® SCX column. The column was washed with MeOH. Subsequently, the compound was eluted with NH3-MeOH, and the recovered fraction was concentrated under reduced pressure to obtain (2R)-4-(-{5-chloro-2-[(3R)-3-methylpiperazin-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide as an off-white solid (33 mg, 95.35%). [ka] HPLC RT(B2) 7.23 min; LCMS MH + 469

[0340] (Example 2) [ka] (1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) A solution of 1-(2,5-dichloropyrimidine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide (intermediate 1, 50 mg, 0.12 mmol) and [(3S)-1,3-dimethylpiperazine bis-TFA salt (211 mg, 0.61 mmol) in n-butanol (0.7 mL) was treated with triethylamine (0.17 mL, 1.23 mmol), and then heated at 160°C for 160 minutes under microwave irradiation. The reaction mixture was evaporated under reduced pressure, and the crude product was purified by preparative TLC after elution with 9% MeOH in DCM, yielding 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazin-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide as a pale yellow solid (27 mg, 45%). [ka] HPLC RT(B1) 7.16 min; LCMS MH + 483. HRMS observed value 483.2384, calculated value 483.288(C 24 H 32 ClN8O)

[0341] (Example 2A) (1-{5-chloro-2-[(2R)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) Example 2A can be prepared from a suitable chloropyrimidine intermediate and a Boc-protected diamine using the same method as in Example 2.

[0342] (Example 3) [ka] (1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) To a MeOH (6 mL) stirred solution of 1-{5-chloro-2-[(3R)-3-methylpiperazin-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamidobis-TFA salt ((Example 1), 800 mg, 1.15 mmol), HCHO solution (37% in H2O, 172 μL, 5.7 mmol) was added, and the mixture was stirred at RT for 1 hour. Then, NaCNBH3 (214 mg, 3.5 mmol) was added at 0°C, and the reaction mixture was stirred at RT for 16 hours.

[0343] The reaction mixture was quenched with NaHCO3 solution and extracted with DCM. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. Purification of the crude product by preparative TLC (6% MeOH in DCM) yielded 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazin-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide as an off-white solid (320 mg, 58%). [ka] HPLC RT(A1) 4.89 min; LCMS MH + 483. HRMS observed value 483.2387, calculated value 483.288(C 24 H 32 ClN8O).

[0344] (Example 4) [ka] (1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyridine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide) A solution of 1-(2-chloro-5-fluoropyridine-4-yl)-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide (intermediate 2, 90 mg, 0.23 mmol), 1-methylpiperazine (69 mg, 0.69 mmol), and cesium carbonate (377 mg, 1.16 mmol) in dimethoxyethane (DME, 3 mL) was purged with argon for 10 minutes, after which Pd2(dba)3 (42.6 mg, 0.046 mmol) and SPhOs (49.5 mg, 0.12 mmol) were added. After further purging with argon for 5 minutes, the mixture was heated at 120°C for 16 hours. The reaction mixture was extracted with ELISA, washed with water and brine, dried on Na2SO4, and evaporated under vacuum. Subsequently, the crude product was purified by combiflush chromatography using elution with 3% MeOH in DCM, yielding 1-[5-fluoro-2-(4-methylpiperazin-1-yl)pyridine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide as an off-white solid (30 mg, 29%). [ka] HPLC RT(A2) 5.58 min; LCMS MH + 452.

[0345] Examples 5-51 and 112 were prepared from a suitable chloropyrimidine intermediate and a Boc-protected diamine using the same method as in Example 1. Table 2 [Table 5] TIFF0007843754000115.tif220170TIFF0007843754000116.tif235170TIFF0007843754000117.tif245170TIFF0007843754000118.tif242170TIFF000 7843754000119.tif245170TIFF0007843754000120.tif245170TIFF0007843754000121.tif245170TIFF0007843754000122.tif243170TIFF0007843754 000123.tif249170TIFF0007843754000124.tif224170TIFF0007843754000125.tif246170TIFF0007843754000126.tif241170TIFF0007843754000127. tif247170TIFF0007843754000128.tif246170TIFF0007843754000129.tif246170TIFF0007843754000130.tif222170TIFF0007843754000131.tif85170

[0346] Examples 52-80 were prepared from suitable chloropyrimidine intermediates and diamines using the same method as in Example 2. Table 3 [Table 6] TIFF0007843754000133.tif238170TIFF0007843754000134.tif220170TIFF000 7843754000135.tif229170TIFF0007843754000136.tif219170TIFF00078437540 00137.tif237170TIFF0007843754000138.tif247170TIFF0007843754000139.t if248170TIFF0007843754000140.tif244170TIFF0007843754000141.tif234170

[0347] Examples 81-102 were prepared from a suitable secondary amine intermediate and formaldehyde by the same method as in Example 3. Examples 103 and 104 were prepared by the method of Example 4 (Buchwaldamine substitution on chloropyridine), followed by Boc deprotection (Example 1), and then by the reductive amination method of Example 3. Table 4 [Table 7] TIFF0007843754000143.tif240170TIFF0007843754000144.tif216170TIFF0007843754 000145.tif244170TIFF0007843754000146.tif234170TIFF0007843754000147.tif23817 0TIFF0007843754000148.tif245170TIFF0007843754000149.tif248170TIFF0007843754 000150.tif233170TIFF0007843754000151.tif247170TIFF0007843754000152.tif64170

[0348] Examples 105-111 were prepared from suitable chloropyridine or chloropyrimidine intermediates and diamines using the same method as in Example 4. Table 5 [Table 8] TIFF0007843754000154.tif247170TIFF0007843754000155.tif247170TIFF0007843754000156.tif31170

[0349] (HPLC method for Examples 113-158:) Eclipse Extend or XDB 5μm C18 (150×4.6mm), Xbridge 5μm C18 (100×4.6mm), Zorbax Extend 5μm C18 (150×4.6mm), or Shimadzu L Column 2 ODS 5μm C18 (150×4.6mm) columns are used, employing gradient elution of acetonitrile (ACN) in water containing 10mM ammonium acetate over 15 minutes (HPLC B), 17 minutes (B1), or 21 minutes (B2) and 18 minutes (B3). The purity of one example was determined by analytical HPLC using a Poroshell 120 2.7 μm EC18 (100 × 4.6 mm), Luna Omega Polar 3 μm C18 (100 × 4.6 mm), Xbridge 5 μm C18 (150 × 4.6 mm), or Sunfire 5 μm C18 (100 × 4.6 mm) column, using gradient elution of acetonitrile (ACN) in water containing 0.05% trifluoroacetic acid over 12 minutes (HPLC A), 14 minutes (A1), or 17 minutes (A2). The purity of another example was determined by analytical HPLC using a Gemini NX 3 μm C18 (100 × 4.6 mm) column, using gradient elution of acetonitrile in water containing 0.05% formic acid over 12 minutes (A3), 14 minutes (A5), and 16 minutes (A6).

[0350] (Example: 113, Synthesis of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide) (Process 1) [ka] To a solution of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (TFA salt, 300 mg, 0.62 mmol) (product of step 2 of Example 118) in 2-propanol (5 ml), Et3N (0.864 ml, 6.198 mmol) was added at 0°C. Then, 2,4-dichlorothieno[2,3-d]pyrimidine (190.6 mg, 0.93 mmol) was added, and the reaction mixture was stirred at RT for 2 hours. The reaction mixture was evaporated under reduced pressure, diluted with ethyl acetate, and washed with water. The organic layer was separated, dried over Na2SO4, and evaporated under reduced pressure to obtain the crude compound. The crude product was purified using 3% MeOH in DCM by combiflash (12g silica column) to obtain 1-(2-chlorothieno[2,3-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (200 mg, 75.58%). [ka] LCMS(HCOOH:ACN): M+H=427, execution time 3 minutes, Rt=1.41 minutes.

[0351] (Process 2) [ka] A stirred solution of 1-(2-chlorothieno[2,3-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (100 mg, 0.235 mmol) and 1-methyl-1,4-diazepane (0.146 ml, 1.174 mmol) in n-BuOH (0.75 ml) was irradiated in microwaves at 115°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (6% MeOH-DCM) yielded N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide (Example 113) (50 mg, 42.21%) as a white solid. [ka] HPLC RT (Method A6) 3.80 min; LCMS (NH4OAc:ACN): M+H=505, run for 5 minutes, Rt=2.59 min.

[0352] (Example 114: Synthesis of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-4-yl)azetidine-3-carboxamide) (Process 1) [ka] To a solution of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (TFA salt, 300 mg, 0.62 mmol) (product of step 2 of Example 118) in 2-propanol (5 ml), Et3N (0.864 ml, 6.198 mmol) was added at 0°C. Then, 2,4-dichloro-6,7-dihydro-5H-cyclopenta[d]pyrimidine (175.723 mg, 0.93 mmol) was added, and the reaction mixture was stirred at RT for 2 hours. The reaction mixture was evaporated under reduced pressure, diluted with ethyl acetate, and washed with water. The organic layer was separated, dried over Na2SO4, and evaporated under reduced pressure to obtain the crude compound. Purification of the crude product using combiflash (12g silica column) with 3% MeOH in DCM yielded 1-(2-chloro-6,7-dihydro-5H-cyclopenta[d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (170mg, 66.75%); [ka] LCMS(HCOOH:ACN): M+H=411, execution time 3 minutes, Rt=1.34 minutes.

[0353] (Process 2) [ka] A stirred solution of 1-(2-chloro-6,7-dihydro-5H-cyclopenta[d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (11) (100 mg, 0.244 mmol) and 1-methyl-1,4-diazepane (0.15 ml, 1.22 mmol) in n-BuOH (0.75 ml) was irradiated in microwaves at 115°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (6% MeOH-DCM) yielded N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-4-yl)azetidine-3-carboxamide (Example 114) (45 mg, 37.76%) as a white solid; [ka] HPLC RT (Method B3) 7.39 min; LCMS (NH4OAc:ACN): M+H=489, run for 5 minutes, Rt=2.06 min.

[0354] (Example 115: Synthesis of 1-(5-chloro-6-methyl-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide) (Process 1) [ka] To a solution of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (TFA salt, 300 mg, 0.62 mmol) (product of step 2 of Example 118) in 2-propanol (5 ml), Et3N (0.864 ml, 6.198 mmol) was added at 0°C. Then, 2,4,5-trichloro-6-methylpyrimidine (183.161 mg, 0.93 mmol) was added, and the reaction mixture was stirred at RT for 2 hours. The reaction mixture was evaporated under reduced pressure, diluted with ethyl acetate, and washed with water. The organic layer was separated, dried over Na2SO4, and evaporated under reduced pressure to obtain the crude compound. When the crude product was purified by combiflash (12g silica column) using 3% MeOH in DCM, 1-(2,5-dichloro-6-methylpyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (200mg, 76.95%) was obtained. [ka] LCMS(HCOOH:ACN): M+H=419, execution time 3 minutes, Rt=1.67 minutes.

[0355] (Process 2) [ka] A stirred solution of 1-(2,5-dichloro-6-methylpyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (100 mg, 0.239 mmol) and 1-methyl-1,4-diazepane (7) (0.15 ml, 1.196 mmol) in n-BuOH (0.75 ml) was irradiated in microwaves at 115°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (6% MeOH-DCM) yielded 1-(5-chloro-6-methyl-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (Example 115) (60 mg, 50.46%) as a white solid. [ka] HPLC RT (Method B3) 7.41 min; LCMS(NH4OAc:ACN): M+H=497, Rt=2.95 minutes after 5 minutes of execution.

[0356] (Example 116: Synthesis of 1-(2-chloro-6-methylthieno[3,2-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide) (Process 1) [ka] To a solution of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (TFA salt, 300 mg, 0.62 mmol) (product of step 2 of Example 118) in 2-propanol (5 ml), Et3N (0.864 ml, 6.198 mmol) was added at 0°C. Then, 2,4-dichloro-6-methylthieno[3,2-d]pyrimidine (203.616 mg, 0.93 mmol) was added, and the reaction mixture was stirred at RT for 2 hours. The reaction mixture was evaporated under reduced pressure, diluted with ethyl acetate, and washed with water. The organic layer was separated, dried over Na2SO4, and evaporated under reduced pressure to obtain the crude compound. When the crude product was purified by combiflash (12g silica column) using 3% MeOH in DCM, 1-(2-chloro-6-methylthieno[3,2-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (200mg, 73.18%) was obtained. [ka] LCMS(HCOOH:ACN): M+H=441, execution time 3 minutes, Rt=1.42 minutes.

[0357] (Process 2) [ka] A stirred solution of 1-(2-chloro-6-methylthieno[3,2-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (100 mg, 0.227 mmol) and 1-methyl-1,4-diazepane (0.141 ml, 1.136 mmol) in n-BuOH (0.75 ml) was irradiated in microwaves at 115°C for 1 hour. The reaction mixture R The solution was cooled to 1°C and concentrated under reduced pressure. Purification of the crude product by preparative TLC (6% MeOH-DCM) yielded N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(6-methyl-2-(4-methyl-1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide (Example 116) (50 mg, 42.42%) as an off-white solid. [ka] HPLC RT (Method A4) 5.04 min; LCMS (NH4OAc:ACN): M+H=519, run for 5 minutes, Rt=2.62 min.

[0358] (Example 117: Synthesis of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(6-methyl-2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide) (Process 1) [ka] To a solution of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (TFA salt, 300 mg, 0.62 mmol) (product of step 2 of Example 118) in 2-propanol (5 ml), Et3N (0.864 ml, 6.198 mmol) was added at 0°C. Then, 2,4-dichloro-6-methylthieno[2,3-d]pyrimidine (203.616 mg, 0.93 mmol) was added, and the reaction mixture was stirred at RT for 2 hours. The reaction mixture was evaporated under reduced pressure, diluted with ethyl acetate, and washed with water. The organic layer was separated, dried over Na2SO4, and evaporated under reduced pressure to obtain the crude compound. When the crude product was purified by combiflash (12g silica column) using 3% MeOH in DCM, 1-(2-chloro-6-methylthieno[2,3-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (180mg, 65.86%) was obtained. [ka] (Methyl 3H peak overlapping with 2.5 ppm DMSO peak); LCMS (HCOOH:ACN): M+H=441, run for 3 minutes, Rt=1.41 minutes.

[0359] (Process 2) [ka] A stirred solution of 1-(2-chloro-6-methylthieno[2,3-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (100 mg, 0.227 mmol) and 1-methyl-1,4-diazepane (0.141 ml, 1.136 mmol) in n-BuOH (0.75 ml) was irradiated in microwaves at 115°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (6% MeOH-DCM) yielded N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(6-methyl-2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide (Example 117) (40 mg, 33.93%) as an off-white solid. [ka] HPLC RT (Method A6) 3.92 min; LCMS (NH4OAc:ACN): M+H=519, run for 5 minutes, Rt=2.71 min.

[0360] (Example 118: Synthesis of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-yl)azetidine-3-carboxamide) (Process 1) [ka] Et3N (3.47 mL, 24.876 mmol) was added to a solution of 2-(imidazo[1,2-a]pyridine-3-yl)propan-2-amine (0.87 g, 4.975 mmol) and 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (1 g, 4.975 mmol) in THF (30 mL). Then, T3P® (50%, 8.9 mL, 14.925 mmol) was added and the mixture was stirred at RT for 16 hours. The reaction mixture was quenched with NaHCO3 solution and extracted with RINKAN. The organic layer was washed with water, dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography by elution with 6% MeOH in DCM to obtain tert-butyl 3-((2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)carbamoyl)azetidine-1-carboxylate (1.4 g, 78.51%) as an off-white solid. LCMS (HCOOH:ACN): M+H=359, run for 3 minutes, Rt=1.33 minutes.

[0361] (Process 2) [ka] To a 30 ml solution of tert-butyl 3-((2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)carbamoyl)azetidine-1-carboxylate (1.95 g, 5.44 mmol), trifluoroacetic acid (4.16 ml, 54.404 mmol) was added at 0°C. The reaction mixture was stirred at RT for 4 hours. When the reaction mixture was concentrated under reduced pressure, N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (2.6 g, 98.74%) was obtained as the TFA salt. [ka] LCMS (HCOOH:ACN): M+H=259, execution time 3 minutes, Rt=0.2 minutes.

[0362] (Step 3) [ka] To a solution of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (TFA salt, 300 mg, 0.62 mmol) in 2-propanol (5 ml), Et3N (0.864 ml, 6.198 mmol) was added at 0°C. Subsequently, 2,4-dichloroquinazoline (185 mg, 0.93 mmol) was added, and the reaction mixture was stirred at RT for 2 hours. The reaction mixture was evaporated under reduced pressure, diluted with ethyl acetate, and washed with water. The organic layer was separated, dried over Na2SO4, and evaporated under reduced pressure to obtain the crude compound. When the crude product was purified using a preparative TLC plate with 3% MeOH in DCM, 1-(2-chloroquinazolin-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (100 mg, 38.33%) was obtained. [ka] LCMS (HCOOH:ACN): M+H=421, execution time 3 minutes, Rt=1.45 minutes.

[0363] (Step 4) [ka] A stirred solution of 1-(2-chloroquinazolin-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (75 mg, 0.179 mmol) and 1-methyl-1,4-diazepane (0.111 ml, 0.893 mmol) in n-BuOH (0.75 ml) was irradiated in microwaves at 115°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (6% MeOH-DCM) yielded N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-yl)azetidine-3-carboxamide (Example 118) (30 mg, 33.7%) as a white solid. [ka] (2H peak overlapping with 2.50 ppm DMSO peak); HPLC RT (Method A4) 4.86 min; LCMS (ACN:HCOOH): M+H=499, run for 5 mins, Rt=1.63 min.

[0364] (Example 119: Synthesis of 1-(5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide) (Process 1) [ka] A stirred solution of 1-(2,5-dichloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide (intermediate 28) (100 mg, 0.235 mmol) and tert-butylpiperazine-1-carboxylate (245 mg, 1.315 mmol) in n-BuOH (1 ml) was irradiated in microwaves at 130°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (4% MeOH-DCM) yielded tert-butyl 4-(5-chloro-4-(3-((2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)(methyl)carbamoyl)azetidine-1-yl)pyrimidine-2-yl)piperazine-1-carboxylate (90 mg, 60.11%). [ka]

[0365] (Process 2) [ka] A stirred solution of tert-butyl 4-(5-chloro-4-(3-((2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)(methyl)carbamoyl)azetidine-1-yl)pyrimidine-2-yl)piperazine-1-carboxylate (110 mg, 0.194 mmol) in DCM (2 mL) was treated with TFA (0.221 mL, 1.936 mmol). The reaction mixture was stirred at room temperature for 4 hours. The crude product was dissolved in MeOH and packed into an Isolute® SCX column. The column was washed with MeOH. Subsequently, the compound was eluted with NH3-MeOH, and the recovered fraction was concentrated under reduced pressure to obtain 1-(5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide (Example 119) as an off-white, sticky solid (46 mg, 50.67%). [ka] HPLC RT (Method B3) 7.54 min; LCMS (NH4OAc:ACN): M+H=469, run for 5 minutes, Rt=2.13 min.

[0366] (Example 120: Synthesis of 1-(5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide) (Process 1) [ka] A stirred solution of 1-(2,5-dichloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide (intermediate 28) (125 mg, 0.299 mmol) and tert-butyl 1,4-diazepan-1-carboxylate (178 mg, 1.495 mmol) in n-BuOH (2 ml) was irradiated in microwaves at 130°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (4% MeOH-DCM) yielded tert-butyl 4-(5-chloro-4-(3-((2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)(methyl)carbamoyl)azetidine-1-yl)pyrimidine-2-yl)-1,4-diazepan-1-carboxylate (80 mg, 45.89%). [ka]

[0367] (Process 2) [ka] A stirred solution of tert-butyl 4-(5-chloro-4-(3-((2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)(methyl)carbamoyl)azetidine-1-yl)pyrimidine-2-yl)-1,4-diazepan-1-carboxylate (85 mg, 0.146 mmol) in DCM (2 mL) was treated with TFA (0.166 mL, 1.457 mmol). The reaction mixture was stirred at room temperature for 4 hours. The crude product was dissolved in MeOH and packed into an Isolute® SCX column. The column was washed with MeOH. Subsequently, the compound was eluted with NH3-MeOH, and the recovered fraction was concentrated under reduced pressure to obtain 1-(5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide (Example 120) as an off-white, sticky solid (30 mg, 42.62%). [ka] HPLC RT (Method B3) 7.59 min; LCMS (NH4OAc:ACN): M+H=483, run for 5 minutes, Rt=2.17 min.

[0368] (Example 121: Synthesis of 1-(5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide) [ka] A stirred solution of 1-(2,5-dichloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide (intermediate 28) (60 mg, 0.144 mmol) and 1-methyl-1,4-diazepane (82 mg, 0.718 mmol) in n-BuOH (1 ml) was irradiated in microwaves at 130°C for 1 hour. The reaction mixture was cooled to RT and concentrated under reduced pressure. Purification of the crude product by preparative TLC (4% MeOH-DCM) yielded 1-(5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide (Example 121) (32 mg, 44.88%). [ka] HPLC RT (Method A4) 4.70 min; LCMS (NH4OAc:ACN): M+H=497, run for 5 minutes, Rt=2.65 min.

[0369] (Example 122: Synthesis of N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methyl-1-(2-(4-methyl-1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide) (Process 1) [ka] To a 5 ml stirred solution of 1-(2-chlorothieno[3,2-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide (500 mg, 1.235 mmol) (product of step 1 of Example 123) in DMF, NaH (60%, 74 mg, 1.852 mmol) was added at 0°C and the mixture was stirred for 30 minutes. Then, methyl iodide (210 mg, 1.481 mmol) was added to the reaction mixture, and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was then quenched with ice water and extracted with butyl. The organic layer was dried over Na2SO4, filtered, and concentrated to obtain the crude product. The crude product was purified by combiflash column chromatography (12g silica column) using MeOH in DCM to obtain 1-(2-chlorothieno[3,2-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetid...

Claims

1. Compounds of formula (I), or pharmaceutically acceptable salts thereof: 【Chemistry 1】 (In the formula: n 1 is 1 or 2; n 2 is 1 or 2; X 1 It is selected from the group consisting of CH and N; R1 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups; R 2 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups; R3 is a -C atom optionally substituted with hydrogen and one, two, or three F atoms. 1-4 Selected from the group consisting of alkyl groups; X 2 is CR 4 Selected from the group consisting of and N; When present, R 4 is selected from the group consisting of hydrogen; halogen; and -C 1-4 alkyl; R 5a and R 5d hydrogen; halogen; each substituent is halogen, -OH, -OCH 3 , and -OCF 3 Methyl molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of; and each substituent being a halogen, -OH, -OCH 3 , and -OCF 3 Independently selected from the group consisting of methoxy molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of; R 5b and R 5c This includes hydrogen; halogens; and each substituent being a halogen, -OH, or -OCH 3 , and -OCF 3 -C which is optionally substituted with one, two, or three substituents independently selected from the group consisting of 1-4 Independently selected from the group consisting of alkyl groups; R 6 is selected from the group consisting of hydrogen and methyl; If present, each R 7 is -C 1-4 It is alkyl; R 8 This refers to hydrogen; halogen; -OH; -CN; and -C, which is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkyl; each substituent is a halogen, -CH 3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of -OH, -CN, and methoxy optionally substituted with one, two, or three halogens. 3-6 Cycloalkyl; -C, where each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Alkenyls; and -OCs, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, CN, and methoxy molecules optionally substituted with one, two, or three halogens. 1-4 Selected from the group consisting of alkyl groups; R 9 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups; or R 8 and R 9 These are six-membered aryl groups containing one or two heteroatoms selected from N, O, and S, along with the atoms to which they are bonded, and C 5-6 They are linked to form a cycloalkyl group or a 5 or 6-membered aromatic heterocyclyl group, where the 6-membered aryl group, C 5-6 Cycloalkyl groups, or 5- to 6-membered aromatic heterocyclyl groups, each substituent is optionally substituted with halogens; -OH; -CN; -C1-3 alkyl groups, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and -O-C1-3 alkyl groups, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of -halogens, -OH, -OCH3, and -OCF3; p is 0, 1, or 2; Z is 【Chemistry 2】 A 5- to 13-membered non-aromatic heterocyclyl group selected from (wherein the formula, 【Transformation 3】 This represents a point of connection, m is either 1 or 2; r is 0, 1, or 2; s is 0, 1, or 2; R 12 is selected from the group consisting of hydrogen and -C 1-6 alkyl groups, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and -OC 1-3 alkyl groups; If present, each R13 is a halogen; each substituent is a halogen, -OH, and -OC. 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; each substituent is a halogen, -OH, and -OC. 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; NR c R d ; and each substituent is a halogen, -OH, and -OC 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 They are independently selected from the group consisting of cycloalkyls; or, when two substituents are in adjacent ring positions, they contain a C heteroatom selected from the group consisting of O and N, together with the atom to which they are bonded. 3-6 They may be linked to form a cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group, where the C 3-6 Cycloalkyl groups or 4-6 member non-aromatic heterocyclyl groups: each substituent is a halogen; each substituent is a halogen, -OH, and -OC. 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and each substituent being a halogen, -OH, and -OC 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups. R c and R d is hydrogen; -C 1-6 alkyl; place C 3-6 Independently selected from the group consisting of cycloalkyl; and If present, each R 14 is a halogen; an -C 1-6 alkyl group in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, and -OC 1-3 alkyl groups; and an -OC 1-6 alkyl group in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, and -OC 1-3 alkyl groups); Alternatively, Z is -NR 10 R 11 And here, R 10 is hydrogen and -C 1-4 Selected from the group consisting of alkyl; and R 11 is a 5 or 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N and O, wherein at least one of the heteroatoms is N, and wherein the 5 or 6-membered non-aromatic heterocyclyl group is a halogen; -OH; and each substituent is a halogen, -OH, and -OC 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and each substituent being a halogen, -OH, and -OC 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 (Optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups).

2. The following are the compounds described in claim 1 or pharmaceutically acceptable salts thereof: 【Chemistry 4】 (In the formula: n 1 is 1 or 2; n 2 is 1 or 2; X 1 It is selected from the group consisting of CH and N; R1 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups; R 2 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups; R3 is a -C atom optionally substituted with hydrogen and one, two, or three F atoms. 1-4 Selected from the group consisting of alkyl groups; X 2 is CR 4 Selected from the group consisting of and N; If present, R 4 hydrogen; halogens; and -C 1-4 Selected from the group consisting of alkyl groups; R 5a and R 5d hydrogen; halogen; each substituent is halogen, -OH, -OCH 3 , and -OCF 3 Methyl molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of; and each substituent being a halogen, -OH, -OCH 3 , and -OCF 3 Independently selected from the group consisting of methoxy molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of; R 5b and R 5c This includes hydrogen; halogens; and each substituent being a halogen, -OH, or -OCH 3 , and -OCF 3 -C which is optionally substituted with one, two, or three substituents independently selected from the group consisting of 1-4 Independently selected from the group consisting of alkyl groups; R 6 is selected from the group consisting of hydrogen and methyl; If present, each R 7 is -C 1-4 It is alkyl; R 8 is independently selected from the group consisting of hydrogen; halogen; -OH; -CN; and -C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -OH, -CN, and methoxy optionally substituted by 1, 2, or 3 halogens 1-4 alkyl; and -C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -CH 3 , -OH, -CN, and methoxy optionally substituted by 1, 2, or 3 halogens 3-6 cycloalkyl; and -C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -OH, -CN, and methoxy optionally substituted by 1, 2, or 3 halogens 1-4 alkenyl; and -O-C optionally substituted by one, two, or three substituents each independently selected from the group consisting of halogen, -OH, CN, and methoxy optionally substituted by 1, 2, or 3 halogens 1-4 and is selected from the group consisting of alkyl; R 9 is hydrogen and -C 1-4 Selected from the group consisting of alkyl groups; or R 8 and R 9 They are linked together with the atoms to which they are bonded so as to form a 6-membered aryl group or a 5- or 6-membered aromatic heterocyclyl group comprising one or two heteroatoms selected from N, O, and S, wherein the 6-membered aryl group or 5- to 6-membered aromatic heterocyclyl group is optionally substituted with halogens; -OH; -CN; -C1-3 alkyl groups, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, -OCH3, and -OCF3; and -O-C1-3 alkyl groups, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, and -OCH3, and -OCF3; p is 0, 1, or 2; Z is 【Transformation 5】 A 5- to 13-membered non-aromatic heterocyclyl group selected from (wherein the formula, 【Transformation 6】 This represents a point of connection, m is either 1 or 2; r is 0, 1, or 2; s is 0, 1, or 2; R 12 is selected from the group consisting of hydrogen and -C 1-6 alkyl groups, each substituent optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens and -OC 1-3 alkyl groups; When present, each R13 is halogen; -C optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen, -OH, and -OC 1-3 alkyl; and each -O-C optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen, -OH, and -O-C 1-6 alkyl; and each -O-C optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen, -OH, and -O-C 1-3 alkyl; and each -O-C optionally substituted by one, two, or three substituents independently selected from the group consisting of halogen, -OH, and -O-C 1-6 is independently selected from the group consisting of alkyl; and If present, each R 14 is a halogen; an -C 1-6 alkyl group in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, and -OC 1-3 alkyl groups; and an -OC 1-6 alkyl group in which each substituent is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogens, -OH, and -OC 1-3 alkyl groups); Or Z is -NR 10 R 11 And here, R 10 is hydrogen and -C 1-4 Selected from the group consisting of alkyl; and R 11 is a 5 or 6-membered non-aromatic heterocyclyl group comprising one or two heteroatoms selected from N and O, wherein at least one of the heteroatoms is N, and wherein the 5 or 6-membered non-aromatic heterocyclyl group is a halogen; -OH; and each substituent is a halogen, -OH, and -OC 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and each substituent being a halogen, -OH, and -OC 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 (Optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups).

3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein Z is an optionally substituted 5- to 8-membered non-aromatic heterocycline group.

4. Z 【Transformation 7】 (Here, 【Transformation 8】 represents a junction; m is either 1 or 2; r is 0, 1, or 2; s is 0, 1, or 2; R 12 This is hydrogen and each substituent is a halogen and -OC 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Selected from the group consisting of alkyl; and If present, each R 13 is a halogen; each substituent is a halogen, -OH, and -OC. 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and each substituent being a halogen, -OH, and -OC 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; NR c R d ; and each substituent is a halogen, -OH, and -OC 1-3 C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 3-6 They are independently selected from the group consisting of cycloalkyls; or, when two substituents are in adjacent ring positions, they contain a C heteroatom selected from the group consisting of O and N, together with the atom to which they are bonded. 3-6 They may be linked to form a cycloalkyl group or a 4-6 membered non-aromatic heterocyclyl group, where the C 3-6 Cycloalkyl groups or 4-6 member non-aromatic heterocyclyl groups: each substituent is a halogen; each substituent is a halogen, -OH, and -OC. 1-3 -C is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 Alkyl; and each substituent being a halogen, -OH, and -OC 1-3 -OC molecules optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 It is optionally substituted with one or two substituents independently selected from the group consisting of alkyl groups; R c and R d is hydrogen; -C 1-6 alkyl; place C 3-6 Independently selected from the group consisting of cycloalkyl; and If present, each R 14 is a halogen; each substituent is a halogen, -OH, and -OC. 1-3 -C optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups 1-6 Alkyl; and each substituent being a halogen, -OH, and -OC 1-3 -OCs optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl groups. 1-6 (Independently selected from the group consisting of alkyl groups) The compound according to claim 3 or a pharmaceutically acceptable salt thereof.

5. Z 【Chemistry 9】 (Here, 【Chemistry 10】 (This represents a connection point.) A compound according to claim 4 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

6. Z 【Chemistry 11】 (Here, 【Chemistry 12】 (This represents a connection point.) A compound according to claim 5 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

7. R 1 However, -C 1-4 alkyl and R 2 However, -C 1-4 A compound according to any one of claims 1 to 6, which is alkyl, or a pharmaceutically acceptable salt thereof.

8. R 1 is methyl and R 2 The compound according to claim 7, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl.

9. R 8 However, hydrogen, halogen, methyl, CF 3 methoxy, and OCF 3 A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, selected from the group consisting of the above.

10. R 8 The compound according to claim 9, or a pharmaceutically acceptable salt thereof, wherein the compound is Cl.

11. n 1 is 1 and n 2 A compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein the ratio is 1.

12. X 2 CR 4 And R 4 X is selected from the group consisting of hydrogen and methyl, and X 1 A compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein the compound is N.

13. R 5a , R 5b , R 5c , R 5d , R 3 , R 6 , and R 9 A compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein each of the atoms is hydrogen and p is 0.

14. The aforementioned compound or a pharmaceutically acceptable salt thereof: 1-{5-chloro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyridine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-(5-chloro-2-{3,6-diazabicyclo[3.2.0]heptan-3-yl}pyrimidine-4-yl)-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-(2-{3,6-diazabicyclo[3.2.0]heptan-3-yl}-5-fluoropyrimidine-4-yl)-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-fluoropyrimidine-4-yl]-N-({2-methylimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-(2-{3,6-diazabicyclo[3.2.0]heptan-3-yl}-5-fluoropyrimidine-4-yl)-N-({2-methylimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-{5-fluoro-2-[methyl(pyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-fluoro-2-(pyrroridine-3-ylamino)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-fluoro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}-N-methylazetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-({2-methylimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-methoxypyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-methoxypyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-({6-fluoroimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-({6-chloroimidazo[1,2-a]pyridine-3-yl}methyl)azetidine-3-carboxamide; 1-[2-(1,4-diazepan-1-yl)-5-methoxypyrimidine-4-yl]-N-(1-{2-methylimidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(1-{2-methylimidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-fluoro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-fluoro-2-(piperazin-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-fluoro-2-(piperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(piperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methoxy-2-(piperazine-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; 1-{5-fluoro-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R)-3-methylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3S)-3-methylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-fluoro-2-[methyl(pyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[methyl(pyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5S)-3,5-dimethylpiperazine-1-yl]-5-methoxypyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5S)-3,5-dimethylpiperazine-1-yl]-5-chloropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5S)-3,5-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide 1-{2-[(3S,5S)-3,5-dimethylpiperazine-1-yl]-5-methoxypyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5R)-3,5-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R,5R)-3,5-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3S,5S)-3,5-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide 1-[5-fluoro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-[5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[methyl(1-methylpyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[methyl(1-methylpyrrolidine-3-yl)amino]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{8-fluoroimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methoxy-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-3-methylazetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-[5-methyl-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2R)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[3-(fluoromethyl)-4-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-ethylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[4-(propan-2-yl)piperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[4-(2-methoxyethyl)piperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; (3R)-1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; (3S)-1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)piperidine-4-carboxamide; 1-[5-fluoro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(2S,3R)-2,3-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[3-(methoxymethyl)-4-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-(5-fluoro-2-{6-methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl}pyrimidine-4-yl)-N-{imidazo[1,2-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; 1-{2-[(3S)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3S)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-methoxypyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)pyrrolidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-3-methylazetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{6-methylimidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; (3R)-1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; (3S)-1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)pyrrolidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)piperidine-4-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyridine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3R)-3,4-dimethylpiperazine-1-yl]-5-fluoropyridine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyridine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-{imidazo[1,2-a]pyridine-3-ylmethyl}-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{2-[(2S)-2,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{5-chloro-2-[(2S,5R)-2,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(2R,5R)-2,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(2S,5R)-2,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-{[1,2,4]triazolo[4,3-a]pyridine-3-ylmethyl}azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)quinazoline-4-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(4-methyl-1,4-diazepan-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-4-yl)azetidine-3-carboxamide; 1-(5-chloro-6-methyl-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(6-methyl-2-(4-methyl-1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(6-methyl-2-(4-methyl-1,4-diazepan-1-yl)thieno[2,3-d]pyrimidine-4-yl)azetidine-3-carboxamide; 1-(2-(1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(piperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methyl-1-(2-(4-methyl-1,4-diazepan-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; (R)-1-(5-chloro-2-(3-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methyl-1-(2-(2-methylpiperazine-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; (S)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-1-(2-(2-methylpiperazine-1-yl)thieno[3,2-d]pyrimidine-4-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(3,3-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(4-aminopiperidine-1-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(4,7-diazaspiro[2.5]octan-7-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(4-aminoazepan-1-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(2-(3,8-diazabicyclo[3.2.1]octan-3-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(2,3-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methyl-1-(2-(2-methylpiperazine-1-yl)-5-(trifluoromethyl)pyrimidine-4-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(piperazin-1-yl)pyrimidine-4-yl)-N-ethyl-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(3-ethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (R)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (R)-1-(5-chloro-2-(2,4-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-1-(5-chloro-2-(3-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-1-(5-chloro-2-(3,4-dimethylpiperazin-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (R)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-(2,3-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-ethyl-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(2-(3,8-diazabicyclo[3.2.1]octan-3-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propane-2-yl)azetidine-3-carboxamide; 1-(2-(2,5-diazabicyclo[4.1.0]heptan-2-yl)-5-chloropyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-ethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; (S)-1-(5-chloro-2-(2-ethylpiperazin-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide: 1-(5-chloro-2-(2,2-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-(4,7-diazaspiro[2.5]octan-4-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)-N-methylazetidine-3-carboxamide; 1-(5-chloro-2-((2S,5S)-2,5-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-((2S,5S)-2,4,5-trimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-(5-chloro-2-((2S,5R)-2,5-dimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; and 1-(5-chloro-2-((2S,5R)-2,4,5-trimethylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3S,5S)-3,5-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3S,5S)-3,,5-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide 1-{5-chloro-2-[(2R)-2-methylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-N-methylazetidine-3-carboxamide; 1-{2-[(3S)-3,4-dimethylpiperazine-1-yl]-5-methoxypyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propane-2-yl)azetidine-3-carboxamide; 1-{2-[(3S)-3,4-dimethylpiperazine-1-yl]-5-fluoropyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-3-methylazetidine-3-carboxamide; N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)-1-{5-methoxy-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}azetidine-3-carboxamide; 1-{5-chloro-2-[(3S,5S)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-fluoro-2-[(3R,5R)-3,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3S)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)piperidine-4-carboxamide; 1-{5-chloro-2-[(3S)-3,4-dimethylpiperazine-1-yl]pyridine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{2-[(3S)-3,4-dimethylpiperazine-1-yl]-5-fluoropyridine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; and 1-{5-chloro-2-[(2S,5S)-2,4,5-trimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; or any one of the salts that is acceptable as a medicine, A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the above.

15. The aforementioned compound or a pharmaceutically acceptable salt thereof: 1-{5-chloro-2-[(2S)-2,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-{5-chloro-2-[(3R)-3,4-dimethylpiperazine-1-yl]pyrimidine-4-yl}-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; 1-[5-chloro-2-(1,4-diazepan-1-yl)pyrimidine-4-yl]-N-(1-{imidazo[1,2-a]pyridine-3-yl}ethyl)azetidine-3-carboxamide; 1-[5-chloro-2-(4-methylpiperazine-1-yl)pyrimidine-4-yl]-N-(2-{imidazo[1,2-a]pyridine-3-yl}propan-2-yl)azetidine-3-carboxamide; and (S)-1-(5-chloro-2-(2-methylpiperazine-1-yl)pyrimidine-4-yl)-N-(2-(imidazo[1,2-a]pyridine-3-yl)propan-2-yl)azetidine-3-carboxamide; or any one of the salts that is acceptable as a medicine, A compound according to claim 14 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the above.

16. A pharmaceutical composition comprising a compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition according to claim 16, for use as a pharmaceutical.

18. The pharmaceutical composition according to claim 16, for use in the prevention or treatment of a disease or disorder selected from the group consisting of hyperproliferative disorders, viral infections, neurological disorders, ischemia, osteoporosis, diabetes mellitus, autoimmune diseases, inflammatory diseases, and microbial infections.

19. The pharmaceutical composition for use according to claim 18, wherein the disease or disorder is a hyperproliferative disorder, and the hyperproliferative disorder is cancer.

20. The pharmaceutical composition for use according to claim 19, wherein the cancer is colorectal cancer, gallbladder cancer, brain tumor, lymphoma, leukemia, neuroblastoma, hematological malignancy, myeloma, or solid tumor.

21. - Compound of formula (II) 【Chemistry 13】 (In the formula, Q is a nitrogen protecting group and R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , m, p, r, n 1 , n 2 , and R 13 This is as defined in any one of claims 1 to 13; - Compound of formula (V) 【Chemistry 14】 (In the formula, D is a halo and R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , p, n 1 , and n 2 (as defined in any one of claims 1 to 13), A compound selected from the group consisting of the following.

22. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof: 【Chemistry 15】 (In the formula, R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , p, n 1 , and n 2 (This is as defined in any one of claims 1 to 13.) Compound of formula (X): 【Chemistry 16】 or its salt (wherein R 1 , R 2 , R 3 , R 5a , R 5b , R 5c , R 5d , R 6 , R 7 , X 2 , p, n 1 , and n 2 (As defined for compounds of formula (I), for compounds of formula (XI'): 【Chemistry 17】 or its salt (where T is C) 1-6 It is alkyl, and also Z, R 8 , R 9 , and X 1 The process comprises reacting the compound (as defined for the compound of formula (I)) with a base in the presence of a base.

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