Novel heteroaryl-substituted imidazole derivatives

Abstract

The present invention provides novel heteroaryl-substituted imidazole derivatives having the general formula (I), and pharma- ceutically acceptable salts thereof, wherein A and R 1 ~R 6 is as described herein. TIFF2024506021000117.tif5572 Pharmaceutical compositions comprising the compounds, processes for producing the compounds, and methods of using the compounds as medicines, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resultant diseases, are further provided.

Description

[Technical Field]

[0001] Field of Invention The present invention relates to novel imidazole-substituted pyrazole derivatives exhibiting antibacterial properties. The present invention also relates to methods of using these compounds for the treatment or prevention of bacterial infections and resulting diseases, particularly for the treatment or prevention of infections caused by Acinetobacter baumannii and resulting diseases. [Background technology]

[0002] Background of the Invention Acinetobacter baumannii is a Gram-negative, aerobic, non-fermenting bacterium that has been recognized over the past few decades as a novel pathogen with extremely limited treatment options.

[0003] A. baumannii is considered a serious threat by the U.S. Centers for Disease Control and Prevention and currently causes the majority of hospital-acquired infections. It belongs to the group of so-called "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli) that effectively "escape" the activity of antimicrobial agents.

[0004] A. baumannii most frequently occurs in intensive care units and surgical wards, where widespread use of antibiotics allows for selection regarding resistance to all known antimicrobial agents, potentially leading to infections such as bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections.

[0005] A. baumannii possesses an exceptional ability to upregulate and acquire resistance determinants, exhibiting environmental persistence that enables its survival and spread in hospital environments. This often makes the organism a source of infectious disease outbreaks and a regional healthcare-related pathogen.

[0006] Due to increasing antibiotic resistance to most, if not all, available treatment options, multidrug-resistant (MDR) A. baumannii infections, particularly those caused by carbapenem-resistant A. baumannii, are extremely difficult or even impossible to treat, leading to increased morbidity and length of stay in the intensive care unit, as well as high mortality rates. [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] According to the Infectious Diseases Society of America (IDSA) Task Force on Antimicrobial Availability (AATF), Acinetobacter baumannii has been, and remains, considered a prime example of the mismatch between unmet medical needs and the current antimicrobial research and development pipeline. Therefore, there is a high demand and need to identify compounds suitable for treating diseases and infections caused by Acinetobacter baumannii. [Means for solving the problem]

[0008] This invention provides novel compounds that exhibit activity against drug-sensitive and drug-resistant strains of Acinetobacter baumannii.

[0009] Summary of the Invention In the first aspect, the present invention relates to a novel heteroaryl-substituted imidazole derivative of formula (I). [ka] or a pharmaceutically acceptable salt thereof (wherein A and R 1 ~R 6 It provides (as described herein).

[0010] In one embodiment, the present invention provides a method for producing a compound of formula (I) described herein or a pharmaceutically acceptable salt thereof, the method being described in any one of schemes 1 to 4 disclosed herein.

[0011] In a further embodiment, the present invention provides a compound of formula (I) described herein, as it is produced according to the method described herein.

[0012] In a further embodiment, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for use as therapeutic agents.

[0013] In a further embodiment, the present invention provides a pharmaceutical composition comprising a compound of formula (I) described herein or a pharmaceutically acceptable salt thereof, and a therapeutically inactive carrier.

[0014] In a further embodiment, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for use as antibiotics. [Modes for carrying out the invention]

[0015] Detailed description of the invention definition Features, integers, characteristics, compounds, chemical parts, or groups described in relation to specific aspects, embodiments, or examples of the present invention should be understood to be applicable to any other aspects, embodiments, or examples described herein, unless they are incompatible. All features disclosed herein (including any appended claims, abstract, and drawings) and / or all steps of any method or process so so disclosed may be combined in any combination, except for combinations in which at least some of such features and / or steps are mutually exclusive. The present invention is not limited to the details of any of the embodiments described above. The present invention extends to any novel features or any novel combination of features disclosed herein (including any appended claims, abstract, and drawings), or any novel steps or any novel combination of any method or process so so disclosed.

[0016] The term "alkyl" refers to a monovalent or polyvalent, for example, monovalent or divalent, linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, e.g., 1, 2, 3, 4, 5, or 6 carbon atoms ("C1-C6 alkyl"). In some embodiments, alkyl groups include 1 to 3 carbon atoms, e.g., 1, 2, or 3 carbon atoms. Some non-limiting examples of alkyl groups include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, isobutyl, sec-butyl, tert-butyl, and 2,2-dimethylpropyl. A particularly preferred but non-limiting example of alkyl is methyl.

[0017] The term "alkoxy" refers to the alkyl group defined above, bonded to the parent molecule via an oxygen atom. Unless otherwise specified, an alkoxy group contains 1 to 6 carbon atoms ("C1-C6 alkoxy"). In some preferred embodiments, the alkoxy group contains 1 to 4 carbon atoms. In yet other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy. A particularly preferred but non-limiting example of an alkoxy is methoxy.

[0018] The terms "halogen" or "halo" refer to fluoro(F), chloro(Cl), bromo(Br), or iodine(I). Preferably, the terms "halogen" or "halo" refer to fluoro(F), chloro(Cl), or bromo(Br). Particularly preferred but non-limiting examples of "halogen" or "halo" are fluoro(F) and chloro(Cl).

[0019] As used herein, the term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or bicyclic hydrocarbon group having 3 to 10 ring carbon atoms ("C3- 10"Cycloalkyl"). In some preferred embodiments, the cycloalkyl group is a saturated monocyclic hydrocarbon group having 3 to 8 ring carbon atoms, more preferably 3 to 6 ring carbon atoms. "Bicyclic cycloalkyl" refers to a cycloalkyl moiety consisting of two saturated carbon rings having two common carbon atoms, i.e., the bridging separating the two rings is either a single bond or a chain of one or two ring atoms, and a spirocyclic moiety, i.e., a cycloalkyl moiety in which the two rings are linked via one common ring atom. Preferably, the cycloalkyl group is a saturated monocyclic hydrocarbon group having 3 to 6 ring carbon atoms, e.g., 3, 4, 5, or 6 carbon atoms. Some non-limiting examples of cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and spiro[2.3]hexane-5-yl. Particularly preferred, but non-limiting, examples of cycloalkyls include cyclobutyl.

[0020] The term "aminoalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by an amino group. Preferably, "aminoalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by amino groups. Preferred, but non-limiting, examples of aminoalkyls are aminomethyl and 1-aminoethyl.

[0021] The term "aminoalkoxy" refers to an alkoxy group in which at least one hydrogen atom of the alkoxy group is replaced by an amino group. Preferably, "aminoalkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkoxy group are replaced by amino groups. Preferred but non-limiting examples of aminoalkoxy are aminomethoxy and 1-aminoethoxy.

[0022] The term "alkoxyalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by an alkoxy group. Preferably, "alkoxyalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by an alkoxy group. A preferred but non-limiting example of an alkoxyalkyl is 2-ethoxyethyl.

[0023] The term "aminoalkoxyalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by an aminoalkoxy group. Preferably, "aminoalkoxyalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by an aminoalkoxy group. A preferred, but non-limiting, example of an aminoalkynyl is 2-(2-aminoethoxy)ethyl.

[0024] The terms "heterocyclyl" or "heterocycloalkyl" refer to a saturated or partially unsaturated monocyclic or bicyclic ring system, preferably a monocyclic ring system, having 3 to 14 ring atoms, preferably 3 to 10 ring atoms, more preferably 3 to 8 ring atoms, where 1, 2, or 3 of the ring atoms are heteroatoms selected from N, O, and S, and the remaining ring atoms are carbon. Preferably, 1 to 2 of the ring atoms are selected from N and O, and the remaining ring atoms are carbon. A "bicyclic heterocyclyl" refers to a heterocyclic portion consisting of two rings having two common ring atoms, i.e., a spirocyclic portion, i.e., a heterocyclic portion in which the two rings are joined via one common ring atom, where the bridging separating the two rings is either a single bond or a chain of one or two ring atoms. Some non-restrictive examples of heterocyclyl groups include azetidine-3-yl, azetidine-2-yl, oxetan-3-yl, oxetan-2-yl, 2-oxopyrrolidine-1-yl, 2-oxopyrrolidine-3-yl, 5-oxopyrrolidine-2-yl, 5-oxopyrrolidine-3-yl, 2-oxo-1-piperidyl, 2-oxo-3-piperidyl, 2-oxo-4-piperidyl, and 6-oxo-2-piperidyl. These include 6-oxo-3-piperidyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, morpholino, morpholin-2-yl, morpholin-3-yl, pyrrolidinyl (e.g., pyrrolidin-3-yl), piperazinyl (e.g., piperazine-1-yl), 3-azabicyclo[3.1.0]hexane-6-yl, or 2,5-diazabicyclo[2.2.1]heptan-2-yl. Particularly preferred, but non-limiting, examples of heterocyclyls include piperidyl, piperazinyl, pyrrolidinyl, and 3-azabicyclo[3.1.0]hexane-6-yl.

[0025] The term "heteroaryl" refers to a monovalent or polyvalent, monocyclic or bicyclic, preferably bicyclic, ring system having a total of 5 to 14 ring members, preferably 5 to 12 ring members, more preferably 5 to 10 ring members, wherein at least one ring in the system is aromatic, and at least one ring in the system contains one or more heteroatoms. Preferably, "heteroaryl" refers to a 5 to 10-membered heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from O, S, and N. Most preferably, "heteroaryl" refers to a 6 to 10-membered heteroaryl containing 1 to 2 heteroatoms independently selected from O and N. Some non-exclusive examples of heteroaryls include 2-pyridyl, 3-pyridyl, 4-pyridyl, indole-1-yl, 1H-indole-2-yl, 1H-indole-3-yl, 1H-indole-4-yl, 1H-indole-5-yl, 1H-indole-6-yl, 1H-indole-7-yl, 1,2-benzoxazole-3-yl, 1,2-benzoxazole-4-yl, 1,2-benzoxazole-5-yl, 1,2-benzoxazole-6-yl, 1,2-benzoxazole-7-yl, 1H-indazole-3-yl, 1 Examples include H-indazole-4-yl, 1H-indazole-5-yl, 1H-indazole-6-yl, 1H-indazole-7-yl, imidazole-1-yl, 1H-imidazole-2-yl, 1H-imidazole-4-yl, 1H-imidazole-5-yl, oxazole-2-yl, oxazole-4-yl, oxazole-5-yl, thiazole-4-yl, 1,2,4-oxadiazole-3-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyrimidine-5-yl, and 2,3-dihydro-1,4-benzodioxynyl. Preferably, "heteroaryl" refers to pyridyl, indolyl, indazolyl, pyrimidinyl, or 2,3-dihydro-1,4-benzodioxynyl. Most preferably, "heteroaryl" refers to pyridyl, indolyl, and indazolyl.

[0026] The term "hydroxy" refers to the -OH group.

[0027] The term "amino" refers to the -NH2 group.

[0028] The term "cyano" refers to the -CN (nitrile) group.

[0029] The term "carbonyl" refers to a carbon radical that has two of the four covalent bonds shared with the oxygen atom (C=O).

[0030] The term "haloalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by a halogen atom, preferably a fluoro atom. Preferably, "haloalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by a halogen atom, most preferably a fluoro atom. Particularly preferred, but non-limiting, examples of haloalkyls are trifluoromethyl, trifluoroethyl, 2-fluoroethyl, and 2,2-difluoroethyl, particularly trifluoromethyl.

[0031] The term "haloalkoxy" refers to an alkoxy group in which at least one hydrogen atom of the alkoxy group is replaced by a halogen atom, preferably a fluoro atom. Preferably, "haloalkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkoxy group are replaced by halogen atoms, most preferably fluoro atoms. Particularly preferred but non-limiting examples of haloalkoxys are difluoromethoxy and trifluoromethoxy.

[0032] The term "hydroxyalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by a hydroxyl group. Preferably, "hydroxyalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms, most preferably one hydrogen atom, are replaced by a hydroxyl group. Preferred, but non-limiting, examples of hydroxyalkyls are hydroxymethyl, hydroxyethyl (e.g., 2-hydroxyethyl), and 3-hydroxy-3-methylbutyl.

[0033] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological efficacy and properties of a free base or free acid, and is not biologically or otherwise undesirable. Salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, particularly hydrochloric acid, and organic acids such as formic acid, acetic acid, 2,2,2-trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, lactic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and N-acetylcysteine. Furthermore, these salts can be prepared by adding an inorganic base or organic base to a free acid. Salts derived from inorganic bases include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, and magnesium salts. Salts derived from organic bases include, but are not limited to, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as salts of isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, and polyimine resins. Certain pharmaceutically acceptable salts of the compound of formula (I) are formate and 2,2,2-trifluoroacetate.

[0034] The compound of formula (I) may contain several chiral centers and may exist as an optically pure enantiomer, a mixture of enantiomers such as a racemate, an optically pure diastereoisomer, a mixture of diastereoisomers, a diastereoisomer racemate, or a mixture of diastereoisomer racemates.

[0035] According to the Cahn-Ingold-Prelog rule, an asymmetric carbon atom can have either an "R" or "S" configuration.

[0036] The term “treatment,” as used herein, includes: (1) suppressing a symptom, disorder, or condition (e.g., in the case of maintenance treatment, stopping, reducing, or delaying the onset or recurrence of at least one clinical symptom or asymptomatic disease); and / or (2) alleviating a condition (i.e., causing a regression of a symptom, disorder, or condition, or at least one of its clinical symptoms or asymptomatics). The benefit to the treated patient is either statistically significant or at least recognizable to the patient or physician. However, it will be understood that when a medicine is administered to a patient to treat a disease, the outcome does not necessarily have to be an effective treatment.

[0037] As used herein, the term “prevention” includes, in mammals, preventing or delaying the onset of clinical symptoms of a condition, disorder or condition that develops in humans who are suffering from or susceptible to a condition, disorder or condition but have not yet experienced or shown any clinical symptoms or asymptomatic symptoms of that condition, disorder or condition.

[0038] As used herein, the term “mammal” includes both humans and non-humans, and includes, but is not limited to, humans, non-human primates, dogs, cats, mice, cattle, horses, and pigs. In a particularly preferred embodiment, the term “mammal” refers to humans.

[0039] The term "nosocomial infection" refers to hospital-acquired infections (HAIs) that are acquired in a hospital or other healthcare facility. To emphasize both hospital and non-hospital settings, they are sometimes instead called healthcare-associated infections (HAIs or HCAIs). Such infections can be acquired in hospitals, nursing homes, rehabilitation facilities, outpatient clinics, or other clinical settings.

[0040] The compound of the present invention In the first aspect, the present invention relates to formula (I) [ka] (wherein R 1 is (i) a group [Chem.] (ii) a group [Chem.] and (iii) a group [Chem.] selected from R 2 is selected from hydrogen, halogen, cyano, C1 - C6 alkyl, C1 - C6 alkoxy, halo C1 - C6 alkyl, and halo C1 - C6 alkoxy, R 3 is selected from C1 - C6 alkyl and halo C1 - C6 alkyl, R 4 , R 5 , and R 6 are each independently selected from hydrogen, halogen, cyano, hydroxy, C1 - C6 alkyl, C1 - C6 alkoxy, halo C1 - C6 alkyl, halo C1 - C6 alkoxy, amino, C1 - C6 alkyl - NH -, and (C1 - C6 alkyl)2N -, R 7 is hydroxy - C1 - C6 alkyl, amino C1 - C6 alkyl, C1 - C6 alkyl - NH - C1 - C6 alkyl -, (C1 - C6 alkyl)2N - C1 - C6 alkyl -, (C1 - C6 alkyl)3N + - C1 - C6 alkyl -, amino C1 - C6 alkoxy - C1 - C6 alkyl, C1 - C6 alkyl - NH - C1 - C6 alkoxy C1 - C6 alkyl -, (C1 - C6 alkyl)2N - C1 - C6 alkoxy - C1 - C6 alkyl, (C 1 - C6 alkyl)3N + - C1 - C6 alkoxy - C1 - C6 alkyl, and the group ; [Chem.] Selected from, R 8 These include hydroxy-C1~C6 alkyl, amino-C1~C6 alkyl, C1~C6 alkyl-NH-C1~C6 alkyl-, (C1~C6 alkyl)2N-C1~C6 alkyl-, and (C1~C6 alkyl)3N + -C1~C6 alkyl-, amino-C1~C6 alkoxy-C1~C6 alkyl, C1~C6 alkyl-NH-C1~C6 alkoxy-C1~C6 alkyl-, (C1~C6 alkyl)2N-C1~C6 alkoxy-C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkoxy-C1~C6 alkyl, and group [ka] Selected from, R 9 and R 11 Each is independently selected from hydrogen and C1-C6 alkyl groups. R 10 These include hydrogen, C1-C6 alkyl, hydroxy C1-C6 alkyl, amino C1-C6 alkyl-, C1-C6 alkyl-NH-C1-C6 alkyl-, (C1-C6 alkyl)2N-C1-C6 alkyl, and (C1-C6 alkyl)3N + Selected from -C1~C6 alkyl-, R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 These are, independently, hydrogen, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, halo C1-C6 alkoxy, hydroxy C1-C6 alkyl, amino C1-C6 alkyl, C1-C6 alkyl-NH-C1-C6 alkyl-, (C1-C6 alkyl)2N-C1-C6 alkyl, and (C1-C6 alkyl)3N + - Selected from C1 to C6 alkyl groups, A is a 5-14 member heteroaryl, B and C are independently 3-14 member heterocycloalkyl and C3-C10 Selected from cycloalkyl groups, X 1 , X 2 , and Y are independently selected from N and CH, m, n, p, and q are each independently either 0 or 1. L 1 and L 2 Each of these is independently selected from carbonyl, -C(O)-C1~C6 alkyl, -C1~C6 alkyl-C(O)-, -NH-C(O)-, and -C(O)-NH-. (However, A is not a pyrazole.) The present invention provides compounds of the same, or pharmaceutically acceptable salts thereof.

[0041] In one embodiment, the present invention is R 1 is the basis [ka] And R 7 , L 1 , X 1 The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein Y, m, and n are as described herein.

[0042] In one embodiment, the present invention is R 1 is the basis [ka] And R 8 , R 9 , L 2 , X 2 The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein p and q are as described herein.

[0043] In one embodiment, the present invention is R 1 is the basis [ka] And R 10 and R 11The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound is as described herein.

[0044] In one embodiment, the present invention is R 1 teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, R 7 (C1~C6 alkyl)2N-C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkyl-, and groups [ka] Selected from, R 8 (C1~C6 alkyl)2N-C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkoxy-C1~C6 alkyl, and group [ka] Selected from, R 9 and R 11 They are both hydrogen, R 10 These are amino-C1~C6 alkyl and (C1~C6 alkyl)3N + Selected from -C1~C6 alkyl-, R 12 These are hydrogen, hydroxyl, amino-C1~C6 alkyl and (C1~C6 alkyl)3N +Selected from -C1~C6 alkyl-, R 13 , R 14 , R 16 , and R 17 Each is independently selected from hydrogen and C1-C6 alkyl groups. R 15 It is hydroxyl, B consists of 3-14 member heterocycloalkyl groups and C3-C 10 Selected from cycloalkyl groups, C is a 3-14 member heterocycloalkyl group. L 1 It is selected from carbonyl, -C1~C6 alkyl-C(O)-, -NH-C(O)-, and -C(O)-NH-. L 2 It is selected from carbonyl and -C(O)-NH-, X 1 and X 2 However, each is independently selected from N and CH, Y is N, m and n are both 1. p and q are both 0, or p and q are both 1. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0045] In a preferred embodiment, the present invention is R 1 is, [ka] And, R 7 is, [ka] And, R 12 is hydrogen or hydroxyl, R 13 and R 14 They are both hydrogen, B is a 3-14 member heterocycloalkyl group. L 1 These are carbonyl or -C1~C6 alkyl-C(O)-, X 1 And Y are both N, m and n are both 1. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0046] In a particularly preferred embodiment, the present invention is R 1 is, [ka] And, R 7 is, [ka] And, R 12 is hydrogen or hydroxyl, R 13 and R 14 They are both hydrogen, B is piperidine or pyrrolidine, L 1 is a carbonyl or -CH2-C(O)-, X 1 And Y are both N, m and n are both 1. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0047] In one embodiment, the present invention is R 7 However, (C1~C6 alkyl)2N-C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkyl-, and groups [ka] This specification provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, selected from, where R 12 , R 13and R 14 is as defined in the present specification.

[0048] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 7 is amino or a group [Chemical formula] [wherein, R 12 , R 13 , X 14 and D are as defined in the present specification].

[0049] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 8 is (C1-C6 alkyl)2N-C1-C6 alkyl-, (C1-C6 alkyl)3N + -C1-C6 alkyl-, (C1-C6 alkyl)3N + -C1-C6 alkoxy-C1-C6 alkyl and a group [Chemical formula] selected from, and wherein R 15 , R 16 , and R 17 are as defined in the present specification.

[0050] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 9 is hydrogen.

[0051] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 10 is selected from amino-C1-C6 alkyl and (C1-C6 alkyl)3N + -C1-C6 alkyl-.

[0052] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R11 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0053] In one embodiment, the present invention is R 12 However, hydrogen, hydroxy, amino-C1~C6 alkyl and (C1~C6 alkyl)3N + This specification provides compounds of formula (I) as described herein, selected from -C1-C6 alkyl-, or pharmaceutically acceptable salts thereof.

[0054] In a preferred embodiment, the present invention is R 12 The present specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen or hydroxyl.

[0055] In one embodiment, the present invention is R 13 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and C1-C6 alkyl groups.

[0056] In a preferred embodiment, the present invention is R 13 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0057] In one embodiment, the present invention is R 14 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and C1-C6 alkyl groups.

[0058] In a preferred embodiment, the present invention is R 14 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0059] In a preferred embodiment, the present invention is R 15 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydroxyl.

[0060] In a preferred embodiment, the present invention is R 16 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and C1-C6 alkyl groups.

[0061] In a preferred embodiment, the present invention is R 17 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and C1-C6 alkyl groups.

[0062] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein both m and n are 1.

[0063] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein p and q are both 0, or p and q are both 1.

[0064] In one embodiment, the present invention is X 1 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from N and CH.

[0065] In a preferred embodiment, the present invention is X 1 This specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the compound is N.

[0066] In a preferred embodiment, the present invention is X 2 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from N and CH.

[0067] In preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein Y is N.

[0068] In one embodiment, the present invention provides that B is a 3-14 member heterocycloalkyl and C3-C 10This specification provides compounds of formula (I) as described herein, selected from cycloalkyl groups, or pharmaceutically acceptable salts thereof.

[0069] In preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein B is a 14-membered heterocycloalkyl group.

[0070] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein B is piperidine or pyrrolidine.

[0071] In preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein C is a 3- to 14-membered heterocycloalkyl group.

[0072] In one embodiment, the present invention is L 1 The present invention provides compounds of formula (I) as described herein, selected from carbonyl, -C1~C6 alkyl-C(O)-, NH-C(O)-, and -C(O)-NH, or pharmaceutically acceptable salts thereof.

[0073] In a preferred embodiment, the present invention is L 1 The present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is a carbonyl or -C1~C6 alkyl-C(O)-.

[0074] In a particularly preferred embodiment, the present invention is L 1 The present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is a carbonyl or -CH2-C(O)-.

[0075] In a preferred embodiment, the present invention is L 2 The present invention provides compounds of formula (I) as described herein, selected from carbonyl and -C(O)-NH-, or pharmaceutically acceptable salts thereof.

[0076] In one embodiment, the present invention is R 2 The present invention provides compounds of formula (I) described herein, which are halogens or C1-C6 alkyl groups, or pharmaceutically acceptable salts thereof.

[0077] In a preferred embodiment, the present invention is R 2 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is a halogen.

[0078] In a particularly preferred embodiment, the present invention is R 2 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is chloro.

[0079] In one embodiment, the present invention is R 2 However, it is a halogen or a C1-C6 alkyl, R 3 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the group is a C1-C6 alkyl group.

[0080] In a preferred embodiment, the present invention is R 2 It is a halogen, R 3 This provides a compound of formula (I) described herein, which is a C1-C6 alkyl compound, or a pharmaceutically acceptable salt thereof.

[0081] In a particularly preferred embodiment, the present invention is R 2 That is chloro, and R 3 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is methyl.

[0082] In a preferred embodiment, the present invention is R 3 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is a halo-C1~C6 alkyl group.

[0083] In a particularly preferred embodiment, the present invention is R 3 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is methyl.

[0084] In one embodiment, the present invention is R 4 The elements are selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)2N-, and halo-C1-C6 alkyl. R 5 The elements are selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, and (C1-C6 alkyl)2N-. R 6 is hydrogen or halogen. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0085] In a preferred embodiment, the present invention is R 4 These are selected from halogens, (C1-C6 alkyl)2N-, and halo-C1-C6 alkyl. R 5 These are selected from hydrogen, halogens, and C1-C6 alkoxys. R 6 is hydrogen or halogen. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0086] In a particularly preferred embodiment, the present invention is R 4 It is selected from fluoro, (methyl)2N-, and CF3. R 5 It is selected from hydrogen, fluoro and methoxy, R 6 is hydrogen or fluorine. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0087] In one embodiment, the present invention is R 4The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)2N-, and halo-C1-C6 alkyl.

[0088] In a preferred embodiment, the present invention is R 4 The present invention provides compounds of formula (I) as described herein, selected from halogens, (C1-C6 alkyl)2N-, and halo-C1-C6 alkyl, or pharmaceutically acceptable salts thereof.

[0089] In a particularly preferred embodiment, the present invention is R 4 The present invention provides compounds of formula (I) as described herein, selected from fluoro, (methyl)2N-, and CF3, or pharmaceutically acceptable salts thereof.

[0090] In one embodiment, the present invention is R 5 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, and (C1-C6 alkyl)2N-.

[0091] In a preferred embodiment, the present invention is R 5 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, halogens, and C1-C6 alkoxys.

[0092] In a particularly preferred embodiment, the present invention is R 5 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen, fluoro, and methoxy.

[0093] In a preferred embodiment, the present invention is R 6 The present specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is hydrogen or a halogen.

[0094] In a particularly preferred embodiment, the present invention is R 6 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen or fluoro.

[0095] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is a 6- to 14-membered heteroaryl compound.

[0096] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein A is a 6- to 9-membered heteroaryl compound.

[0097] In another preferred embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, in which A is selected from pyridyl, indolyl, indazolyl, pyrimidinyl, and 2,3-dihydro-1,4-benzodioxynyl.

[0098] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein A is selected from pyridyl, indolyl, and indazolyl.

[0099] In one embodiment, the present invention is A is a 6- to 9-membered heteroaryl, R 4 The elements are selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)2N-, and halo-C1-C6 alkyl. R 5 The elements are selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, and (C1-C6 alkyl)2N-. R 6 is hydrogen or halogen. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0100] In a preferred embodiment, the present invention is A is a 6- to 9-membered heteroaryl compound, R 4 These are selected from halogens, (C1-C6 alkyl)2N-, and halo-C1-C6 alkyl. R 5 These are selected from hydrogen, halogens, and C1-C6 alkoxys. R 6 is hydrogen or halogen. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0101] In a particularly preferred embodiment, the present invention is A is selected from pyridyl, indolyl, and indazolyl. R 4 It is selected from fluoro, (methyl)2N-, and CF3. R 5 It is selected from hydrogen, fluoro and methoxy, R 6 is hydrogen or fluorine. This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof.

[0102] In one embodiment, the present invention is R 1 teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, R 2 These are halogens or C1-C6 alkyl groups. R 3 These are C1-C6 alkyl groups, R 4The elements are selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-NH-, (C1-C6 alkyl)2N-, and halo-C1-C6 alkyl. R 5 The elements are selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, and (C1-C6 alkyl)2N-. R 6 is hydrogen or halogen, R 7 (C1~C6 alkyl)2N-C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkyl-, and groups [ka] Selected from, R 8 (C1~C6 alkyl)2N-C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkyl-, (C1~C6 alkyl)3N + -C1~C6 alkoxy-C1~C6 alkyl, and group [ka] Selected from, R 9 and R 11 They are both hydrogen, R 10 These are amino-C1~C6 alkyl and (C1~C6 alkyl)3N + Selected from -C1~C6 alkyl-, R 12 These are hydrogen, hydroxyl, amino-C1~C6 alkyl and (C1~C6 alkyl)3N + Selected from -C1~C6 alkyl-, R 13 , R 14 , R 16 , and R 17 Each is independently selected from hydrogen and C1-C6 alkyl groups. R 15 It is hydroxyl, A is such that B is a 6- to 9-member heteroaryl, B is selected from 3- to 14-member heterocycloalkyl and C3-C 10 cycloalkyl, C is a 3- to 14-member heterocycloalkyl, L 1 is selected from carbonyl, -C1-C6 alkyl-C(O)-, -NH-C(O)-, and -C(O)-NH-, L 2 is selected from carbonyl and -C(O)-NH-, X 1 and X 2 are each independently selected from N and CH, Y is N, m and n are both 1, p and q are both 0, or p and q are both 1, There is provided a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof.

[0103] In a preferred embodiment, the present invention R 1 is the group

Chemical formula

Chemical formula

[0104] In a particularly preferred embodiment, the present invention R 1 is the group

Chemical formula

Chemical formula

[0105] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, the compound of formula (I) being selected from the following: Example A1 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(5-fluoro-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; Example A2 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(6-fluoro-3-methyl-1H-indazole-5-yl)-1-methylimidazole-2-carboxamide; Example A3 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-1-methyl-5-[3-(trifluoromethyl)-1H-indazole-5-yl]imidazole-2-carboxamide; Example A4 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(7-methoxy-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; Example A5 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(2,6-dichloro-3-pyridyl)-1-methylimidazole-2-carboxamide; Example A6 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; Example A7 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(2,6-dimethoxy-3-pyridyl)-1-methylimidazole-2-carboxamide; Example A8 5-(5-chloro-2-methoxy-4-pyridyl)-N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methylimidazole-2-carboxamide; Example A9 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[2-(dimethylamino)-4-(trifluoromethyl)pyrimidine-5-yl]-1-methylimidazole-2-carboxamide; Example A10 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2-methoxy-4-(trifluoromethyl)pyrimidine-5-yl]-1-methylimidazole-2-carboxamide; Example A11 5-(5-chloro-1H-indole-4-yl)-N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-1-methylimidazole-2-carboxamide; Example A12 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(1H-indole-4-yl)-1-methylimidazole-2-carboxamide; Example A13 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methyl-5-(1-methylindol-4-yl)imidazole-2-carboxamide; Example A14 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidin-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methyl-imidazole-2-carboxamide; Example A15 5-(4-chloro-6-methoxy-3-pyridyl)-N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methyl-imidazole-2-carboxamide; Example A16 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methyl-imidazole-2-carboxamide; Example A17 N-[3-chloro-4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methyl-imidazole-2-carboxamide; Example A18 N-[4-[4-[(1R,5S)-3-azabicyclo[3.1.0]hexane-6-carbonyl]piperazine-1-carbonyl]-3-chloro-phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methyl-imidazole-2-carboxamide; Example A19 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2-(difluoromethyl)-6-methoxy-3-pyridyl]-1-methyl-imidazole-2-carboxamide; Example A20 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-methylimidazole-2-carboxamide; Example B1 N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example C1 N-[3-chloro-4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example C2 N-[4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]-3-methylphenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example C3 N-[3-chloro-4-[[3-[[2-(dimethylamino)acetyl]amino]cyclobutyl]carbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example C4 N-[3-chloro-4-[4-[[2-(dimethylamino)acetyl]amino]piperidine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example D1 [2-[4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperazin-1-yl]-2-oxoethyl]-trimethylammonium; Example D2 [2-[4-[4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]-2-methylbenzoyl]piperazine-1-yl]-2-oxoethyl]-trimethylammonium; Example D3 6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]amino]hexyl-trimethyl-ammonium; Example D4 N-[3-chloro-4-[4-(1,1-dimethylpiperidine-1-ium-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example D5 N-[3-chloro-4-[4-(1,1-dimethylpyrrolidine-1-ium-3-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example D6 N-[3-chloro-4-[4-[(2S,4R)-4-hydroxy-1,1-dimethylpyrrolidine-1-ium-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example D7 N-[3-chloro-4-[4-[2-(1,1-dimethylpiperidine-1-ium-4-yl)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example D8 [2-[[3-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]amino]cyclobutyl]amino]-2-oxo-ethyl]-trimethyl-ammonium; Example D9 [2-[[1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]-4-piperidyl]amino]-2-oxo-ethyl]-trimethyl-ammonium; Example D10 2-[3-[4-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]amino]-1-piperidyl]-3-oxo-propoxy]ethyl-trimethyl-ammonium; Example D11 [3-[4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]cyclobutyl]methyl-trimethyl-ammonium; Example D12 N-[3-chloro-4-[[1-[(2S,4R)-4-hydroxy-1,1-dimethylpyrrolidine-1-ium-2-carbonyl]-4-piperidyl]carbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example D13 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]-N-(1,1-dimethylpyrrolidine-1-ium-3-yl)piperidine-4-carboxamide; Example E1 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methylimidazole-2-carboxamide; Example E2 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example E3 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2-fluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example E4 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2-methyl-3-pyridyl]-1-methylimidazole-2-carboxamide; Example E5 5-[2-chloro-6-(dimethylamino)-3-pyridyl]-N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methylimidazole-2-carboxamide; Example F1 N-[3-chloro-4-[4-(4-hydroxypiperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F2 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F3 N-[3-chloro-4-[4-[2-(4-hydroxy-4-piperidyl)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F4 N-[3-chloro-4-[4-(pyrroridine-3-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F5 N-[3-chloro-4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F6 N-[3-chloro-4-[4-[2-(4-piperidyl)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F7 N-[4-[4-[3-(aminomethyl)cyclobutanecarbonyl]piperazine-1-carbonyl]-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F8 N-[4-[[1-[3-(2-aminoethoxy)propanoyl]-4-piperidyl]carbamoyl]-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; Example F9 N-[3-chloro-4-[[1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]-4-piperidyl]carbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; and Example F10 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]-N-pyrrolidine-3-yl-piperidine-4-carboxamide.

[0106] In preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, the compounds of formula (I) selected from the following: Example A1 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(5-fluoro-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; Example A3 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-1-methyl-5-[3-(trifluoromethyl)-1H-indazole-5-yl]imidazole-2-carboxamide; Example A14 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; Example A17 N-[3-chloro-4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; Example E2 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; and Example F2 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide.

[0107] In one embodiment, the present invention provides pharmaceutically acceptable salts of the compounds of formula (I) described herein, particularly pharmaceutically acceptable salts selected from hydrochloride, fumarate, lactate (particularly derived from L-(+)-lactic acid), tartrate (particularly derived from L-(+)-tartaric acid), and trifluoroacetate. In a more specific embodiment, the present invention provides compounds relating to formula (I) described herein (i.e., as “free base” or “free acid”, respectively).

[0108] In some embodiments, the compound of formula (I) is isotope-labeled by having one or more atoms within it that are replaced by atoms having different atomic masses or mass numbers. Such isotope-labeled (i.e., radioactively labeled) compounds of formula (I) are considered to be within the scope of this disclosure. Examples of isotopes that can be incorporated into the compound of formula (I) are isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, for example. 2 H, 3 H, 11 C, 13 C, 14 C, 13 N, 15 N, 15 O, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 Examples include, but are not limited to, formula (I). Certain isotope-labeled compounds of formula (I), for example, those incorporating radioactive isotopes, are useful for studying the tissue distribution of drugs and / or substrates. Radioactive isotope tritium, i.e., 3 H and carbon-14, that is,14 C is particularly useful for this purpose, considering its ease of incorporation and immediate detection means. For example, the compound of formula (I) can be concentrated at 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99% of a given isotope.

[0109] Heavier isotopes, such as deuterium, 2 Substitution with H, etc., can lead to increased metabolic stability, potentially providing specific therapeutic benefits, such as a longer in vivo half-life or a lower required dosage.

[0110] 11 C, 18 F, 15 O, and 13 Substitution with positron-emitting isotopes such as 1N may be useful in positron emission tomography (PET) studies to examine the receptor occupancy of a substrate. Compounds of formula (I) labeled with isotope may be prepared by conventional techniques known to those skilled in the art, or by methods similar to those described in the examples below, using appropriate isotope-labeled reagents instead of previously used unlabeled reagents.

[0111] Manufacturing method The compounds of formula (I) of the present invention can be prepared by sequential or convergent synthetic routes. The synthesis of the compounds of the present invention is shown in the following scheme. The skills required to react and purify the obtained products are known to those skilled in the art. The substituents and indices used in the following process description have the meanings set forth herein unless otherwise indicated. More specifically, the compounds of formula (I) can be prepared by the methods shown below, the methods shown in the examples, or similar methods. Appropriate reaction conditions for each reaction step are known to those skilled in the art. For reaction conditions described in the literature that may affect the reactions described, see, for example, the following: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 3rd Edition, Richard C. Larock, John Wiley & Sons, New York, NY. 2018). The inventors have found it convenient to carry out the reactions in or out of the presence of a solvent. The properties of the solvent used are not particularly limited, as long as it does not adversely affect the reagents involved in the reaction and can dissolve the reagents to at least some extent. The described reactions can occur over a wide range of temperatures, and the exact reaction temperature is not critical to the present invention. It is convenient to carry out the described reactions within a temperature range of -78°C to reflux temperature. The reaction time can also vary considerably, depending on many factors, particularly the reaction temperature and the properties of the reagents. However, a period of 0.5 hours to several days will usually be sufficient to obtain the described intermediates and compounds. The reaction sequence is not limited to the order shown in the scheme, but the order of the reaction steps can be freely changed depending on the starting materials and their respective reactivity. Starting materials can be commercially available or prepared by methods similar to those described below, by methods described in the references or examples cited herein, or by methods known in the art.

[0112] Intermediate A can be prepared according to Scheme 1. By protecting the acid group of nitrobenzoic acid A with a PG group, compound B is obtained. The nitro group is reduced, and amine compound C is obtained using iron chloride / ammonium chloride. Intermediate A is obtained by coupling C and 5-bromo-1-methylimidazole-2-carboxylic acid with a coupling agent such as HATU / DIPEA in DMSO. [ka] In Scheme 1, PG represents an alkyl group, such as Me, Et, or iso-butyl, and R 2 and R 3 This is defined herein.

[0113] Intermediate D can be prepared according to Scheme 2. After deprotection of intermediate A, product D can be coupled with an amine in a solvent such as DMSO in the presence of a coupling agent such as HATU / DIPEA to obtain intermediate B. Deprotection of intermediate B yields intermediate C, which can be further coupled with a carboxylic acid in a solvent such as DMSO in the presence of a coupling agent such as HATU / DIPEA to obtain intermediate D. [ka] In Scheme 2, PG represents an alkyl group, such as Me, Et, or iso-butyl, and R 2 and R 3 This is defined herein. Furthermore, R 1A teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, R 1B teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, R 1C teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, In the formula, X 1 , X 2 Y, m, n, p, q, L 1 , L 2 , and R 7 ~R 11 This is defined as described herein.

[0114] Examples A to E can be prepared according to Scheme 3. The Suzuki coupling of intermediate D with bronic acid or ester (intermediate E or F) is achieved using a palladium catalyst and a phosphine ligand to obtain intermediate J or M. Further deprotection of intermediate J or M yields Examples A to E. In some cases, Examples A to E are further alkylated to obtain quaternary ammonium salt analogs. [ka] In Scheme 3, PG represents an alkyl group, such as Me, Et, or iso-butyl, and R 1 ~R 6 And A is as defined herein. Furthermore, R 1C teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, In the formula, X 1 , X 2 Y, m, n, p, q, L 1 , L 2 , and R 7 ~R 11 This is defined as described herein.

[0115] Examples A to E can also be prepared according to Scheme 4. The Suzuki coupling of intermediate A with bronc acid or an ester (intermediate E or F) is achieved using a palladium catalyst and a phosphine ligand to obtain intermediate O. After deprotecting intermediate O to obtain intermediate H, it is coupled with an amine in the presence of a coupling agent such as HATU / DIPEA in DMSO to obtain intermediate G. Deprotection of intermediate G yields intermediates I, K, or L (in some cases, this step can already give Examples A to E). Intermediate I, K, or L is further coupled with an acid using a coupling agent such as HATU / DIPEA in DMSO to obtain intermediate J or M. Final deprotection of intermediate J or M yields Examples A to E. In some cases, Examples A to E are further alkylated to obtain quaternary ammonium salt analogs. [ka] In Scheme 4, PG represents an alkyl group, such as Me, Et, or iso-butyl, and R 1 ~R 6 And A is as defined herein. Furthermore, R 1A teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, R 1B teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, R 1C teeth, (i) base [ka] (ii) group [ka] and (iii) group [ka] Selected from, In the formula, X 1 , X 2 Y, m, n, p, q, L 1 , L 2 , and R 7 ~R 11 This is defined as described herein.

[0116] In one embodiment, the present invention provides a method for producing a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, the method being described in any one of schemes 1 to 4 disclosed herein.

[0117] In a further embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, when prepared according to the process described herein.

[0118] Use of the compound of the present invention As shown in the experimental section, the compound of formula (I) and its pharmaceutically acceptable salts possess valuable pharmacological properties for the treatment or prevention of infections and resulting diseases caused by pathogens, particularly bacteria, more specifically by Acinetobacter species, and most specifically by Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections.

[0119] The compounds of formula (I) and their pharmaceutically acceptable salts are active as antibiotics, particularly as antibiotics against Acinetobacter species, more specifically as antibiotics against Acinetobacter baumannii, and most specifically as pathogen-specific antibiotics against Acinetobacter baumannii.

[0120] Compounds of formula (I) and pharmaceutically acceptable salts thereof can be used as antibiotics, that is, as appropriate antimicrobial agents in the treatment and prevention of bacterial infections, particularly in the treatment and prevention of bacterial infections caused by Acinetobacter species, and more specifically in the treatment and prevention of bacterial infections caused by Acinetobacter baumannii.

[0121] The compounds of the present invention can be used alone or in combination with other drugs for the treatment or prevention of infections and resulting diseases caused by pathogens, particularly bacteria, more specifically by Acinetobacter species, and most specifically by Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections.

[0122] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

[0123] In a further embodiment, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for use as antibiotics.

[0124] In a further embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, as an antibiotic.

[0125] In a further embodiment, the present invention provides a method for treating or preventing hospital-acquired infections and resulting diseases, the method comprising administering a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, to a mammal.

[0126] In certain embodiments, the hospital-acquired infection and the resulting illness are selected from bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections, or a combination thereof.

[0127] In a further embodiment, the present invention provides a method for treating or preventing infections and resulting diseases caused by Gram-negative bacteria, the method comprising administering a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, to a mammal.

[0128] In one embodiment, the Gram-negative bacteria are selected from Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli (E. coli).

[0129] In certain embodiments, the Gram-negative bacterium is Acinetobacter baumannii.

[0130] In one embodiment, the infection and resulting disease caused by the Gram-negative bacteria are selected from bacteremia, pneumonia, meningitis, urinary tract infections, wound infections, or a combination thereof.

[0131] In a further embodiment, the present invention provides a method for treating or preventing infections and resulting diseases caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, or Escherichia coli (E. coli), or combinations thereof, comprising administering a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, to a mammal.

[0132] In certain embodiments, the infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli (E. coli), or combinations thereof, are selected from bacteremia, pneumonia, meningitis, urinary tract infections and wound infections, or combinations thereof.

[0133] In a further embodiment, the present invention provides a method for treating or preventing bacterial infections and resulting diseases, the method comprising administering a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof, to a mammal.

[0134] In one embodiment, the bacterial infection and the resulting disease are selected from bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections.

[0135] In one embodiment, the bacterial infection and the resulting disease are caused by the Acinetobacter species, most specifically Acinetobacter baumannii.

[0136] In a further embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, in the method described herein.

[0137] In a further embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the methods described herein.

[0138] In a further embodiment, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for preparing a pharmaceutical useful in the method described herein.

[0139] Pharmaceutical composition and administration In one embodiment, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as defined above or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. Exemplary pharmaceutical compositions are described in Examples 1 to 4.

[0140] In a further embodiment, the present invention relates to a pharmaceutical composition comprising a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, for the treatment or prevention of infections and resulting diseases caused by pathogens, particularly bacteria, more specifically Acinetobacter species, most specifically Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections and wound infections.

[0141] Compounds of formula (I) and pharmaceutically acceptable salts thereof may be used as medicines (for example, in the form of pharmaceutical formulations). Pharmaceutical formulations may be administered into the body orally (for example, in the form of tablets, coated tablets, sugar-coated tablets, hard gelatin capsules and soft gelatin capsules, solutions, emulsions or suspensions), nasally (for example, in the form of nasal sprays), or rectally (for example, in the form of suppositories). However, administration may also be carried out parentally, such as intramuscularly or intravenously (for example, in the form of injection solutions or infusion solutions).

[0142] Compounds of formula (I) and pharmaceutically acceptable salts thereof can be treated with pharmaceutically inert inorganic or organic excipients for the manufacture of tablets, coated tablets, sugar-coated tablets, and hard gelatin capsules. Lactose, corn starch or derivatives thereof, talc, stearic acid or salts thereof, etc., can be used as excipients for tablets, sugar-coated tablets, and hard gelatin capsules. Suitable excipients for soft gelatin capsules include, for example, vegetable oils, waxes, fats and oils, semi-solids and liquid polyols.

[0143] Suitable excipients for the manufacture of solutions and syrups include, for example, water, polyols, sucrose, invert sugar, and glucose.

[0144] Suitable excipients for injectable solutions include, for example, water, alcohol, polyol, glycerol, and vegetable oil.

[0145] Suitable excipients for suppositories include, for example, natural or hardened oils, waxes, fats and oils, semi-solid or liquid polyols.

[0146] Furthermore, pharmaceutical preparations may contain preservatives, solubilizers, viscosity enhancers, stabilizers, humectants, emulsifiers, sweeteners, colorants, flavorings, salts to alter osmotic pressure, buffers, masking agents, or antioxidants. Pharmaceutical preparations may also contain other substances of therapeutic value.

[0147] Dosages can vary widely and, of course, are adapted to the individual requirements of each specific case. Generally, for oral administration, a daily dose of approximately 0.1 mg to 20 mg / kg body weight, preferably approximately 0.5 mg to 4 mg / kg body weight (e.g., approximately 300 mg / person), may be appropriately divided into 1 to 3 individual doses, each consisting of, for example, the same amount. However, it is clear that the upper limits given herein can be exceeded where indicated.

[0148] Simultaneous administration of the compound of formula (I) and other drugs. Compounds of formula (I) or salts thereof, or compounds disclosed herein or pharmaceutically acceptable salts thereof, may be used alone or in combination with other agents for treatment. For example, the second agent in a combination pharmaceutical formulation or administration regimen may have complementary activity to the compound of formula (I) so as not to adversely affect each other. The compounds may be administered together or separately in a single pharmaceutical composition. In one embodiment, the compound or pharmaceutically acceptable salt may be administered concurrently with an antibiotic, particularly an antibiotic for the treatment or prevention of infections and resulting diseases caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli (E. coli), or combinations thereof.

[0149] The term "simultaneous administration" refers to the simultaneous administration of a compound of formula (I) or a salt thereof, or a compound disclosed herein or a pharmaceutically acceptable salt thereof, and further active pharmaceutical ingredients, including antibiotics, or any separate sequential administration. If not simultaneous administration, the compounds are administered in close proximity to each other in time. Furthermore, it is not relevant whether the compounds are administered in the same dosage form; for example, one compound may be administered intravenously and another orally.

[0150] Typically, any antimicrobial agent can be administered concurrently. Specific examples of such agents are carbapenems (meropenem), fluoroquinolones (ciprofloxacin), aminoglycosides (amikacin), tetracyclines (tigecycline), colistin, sulbactam, sulbactam + dullobactam, cefiderocol (fetroja), macrocyclic peptides, and macrolides (erythromycin), as exemplified in International Publication Nos. 2017072062A1, 2019185572A1, and 20192068531, respectively.

[0151] In one embodiment, the present invention provides a pharmaceutical composition according to this specification, further comprising an additional therapeutic agent.

[0152] In one embodiment, the present invention provides a pharmaceutically acceptable combination comprising a compound of formula (I) described herein and an additional therapeutic agent.

[0153] In one embodiment, the additional therapeutic agent is an antibiotic preparation.

[0154] In one embodiment, the additional therapeutic agent is an antibiotic preparation useful for treating or preventing infections and resulting diseases caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli (E. coli), or combinations thereof.

[0155] In one embodiment, the additional therapeutic agent is an antibiotic preparation selected from carbapenems (meropenem), fluoroquinolones (ciprofloxacin), aminoglycosides (amikacin), tetracyclines (tigecycline), colistin, sulbactam, sulbactam + durlobactam, cefiderocol (fetroja), macrocyclic peptides, and macrolides (erythromycin), as exemplified in International Publication No. 2017072062A1, International Publication No. 2019185572A1, and International Publication No. 2019206853A1. [Examples]

[0156] The present invention will be better understood by referring to the following embodiments. However, the claims should not be construed as being limited to the scope of these embodiments.

[0157] If the preparation is obtained as a mixture of enantiomers, the pure enantiomers can be separated by the method described herein or by methods known to those skilled in the art, such as chiral chromatography (e.g., chiral SFC) or crystallization.

[0158] Unless otherwise specified, all reaction examples and intermediates were prepared under an argon atmosphere.

[0159] The following abbreviations are used in this specification: ACN or MeCN acetonitrile BINAP 2,2'-bis(diphenylphosphin)-1,1'-binaphthalene CFU Colony-forming units d day DCM Dichloromethane DIPEA N,N-diisopropylethylamine HCl or EA (ethyl acetate) FA Formic Acid h(s) or hr(s) hours HATU:1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate HPLC: High-Performance Liquid Chromatography HPLC-UV: High-performance liquid chromatography with ultraviolet detector IC50 Maximum Half-Dose Inhibitory Concentration IC90 90% inhibitory concentration NaBH3CN Sodium borocyanohydride PE (Petroleum Ether) PdCl2(DPPF)[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd2(dba)3 Tris(dibenzylideneacetone)dipalladium(0) PG protecting group Precat pre-catalyst Preparative HPLC (Preparative High-Performance Liquid Chromatography) rt room temperature sat saturation SEM 2-Methoxyethyl(trimethyl)silane FA Formic Acid TEMPO(2,2,6,6-tetramethylpiperidine-1-yl)oxyl TFA (Trifluoroacetic Acid) wt weight X-PHOS 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

[0160] Intermediate A1 tert-butyl 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoate Step 1: tert-butyl 2-chloro-4-nitro-benzoate A mixture of 2-chloro-4-nitrobenzoic acid (15.0 g, 74.42 mmol), N,N-dimethylpyridine-4-amine (2.73 g, 22.33 mmol), and N,N-diethylethaneamine (31.12 mL, 223.26 mmol) in THF (80 mL) was added at -10°C to a solution of tert-butoxycarbonyl tert-butyl carbonate (24.36 g, 111.63 mmol) in THF (20 mL). The resulting mixture was heated to 25°C and stirred for a further 14 hours. The mixture was concentrated. The residue was treated with EA (50 mL) and H2O (50 mL). The mixture was extracted with EA. The combined organic layer was concentrated. The crude product was then purified by flash column chromatography to obtain 2-chloro-4-nitrobenzoate tert-butyl (18.8 g) as a colorless solid.

[0161] Step 2: tert-butyl 4-amino-2-chlorobenzoate Iron (20.37 g, 364.81 mmol) was added to a mixture of tert-butyl 2-chloro-4-nitro-benzoate (18.8 g, 72.96 mmol) and ammonium chloride (19.51 g, 364.81 mmol) in ethanol (200 mL) and water (200 mL). The mixture was stirred at 25°C for 14 hours. The mixture was filtered through Celite. The filtrate was concentrated to remove ethanol. The mixture was extracted with EA. The combined organic layer was dried over anhydrous Na2SO4 and concentrated to obtain tert-butyl 4-amino-2-chloro-benzoate (16.31 g) as a pale yellow solid. MS [M+H] + :228.1.

[0162] Step 3: tert-butyl 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoate A mixture of 5-bromo-1-methylimidazole-2-carboxylate hydrochloride (7.0 g, 28.99 mmol), tert-butyl 4-amino-2-chlorobenzoate (6.0 g, 26.35 mmol), HATU (13.23 g, 34.79 mmol), and DIPEA (16.16 mL, 92.77 mmol) in DMF (15 mL) was stirred at 25°C for 3 hours. Water (10 mL) was added to the mixture and extracted with EA. The combined organic layer was concentrated. The crude product was purified by FCC to obtain tert-butyl 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoate (8 g, 19.29 mmol) as a white solid. MS [M+H] + :414.0.

[0163] The following intermediates were prepared in the same manner as intermediate A1. [Table 1]

[0164] Intermediate B1 tert-butyl 4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazine-1-carboxylate Step 1: 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoic acid In a 250 mL round-bottom flask, a solution of tert-butyl 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoate (6.5 g, 15.67 mmol) in DCM (30 ml) and TFA (12 ml) was stirred at room temperature for 1 hour. The clear solution was then concentrated under vacuum to obtain 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoic acid (5.5 g) as a pale yellow solid. MS [M+H] + :357.9.

[0165] Step 2: tert-butyl 4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazine-1-carboxylate In a 100 mL round-bottom flask, a mixture of 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoic acid (4.17 g, 11.64 mmol), tert-butylpiperazine-1-carboxylate (4.34 g, 23.3 mmol), HATU (6.64 g, 17.5 mmol), and DIPEA (4.51 g, 34.9 mmol) in DMF (30 mL) was stirred at room temperature for 16 hours. The mixture was then poured into water. The white solid was collected and dried under vacuum to obtain tert-butyl 4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazine-1-carboxylate (5.9 g) as a yellow solid. MS [M+H] + :526.1.

[0166] The following intermediates were prepared in the same manner as intermediate B1. [Table 2]

[0167] Intermediate C1 5-Bromo-N-[3-chloro-4-(piperazine-1-carbonyl)phenyl]-1-methylimidazole-2-carboxamide A solution of tert-butyl 4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazine-1-carboxylate (5.9 g, 11.2 mmol) in DCM (20 ml) and TFA (15 ml) was stirred at room temperature for 30 minutes. The solution was then concentrated and basicized with NH3.H2O. The aqueous layer was extracted with DCM. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under vacuum to obtain 5-bromo-N-[3-chloro-4-(piperazine-1-carbonyl)phenyl]-1-methylimidazole-2-carboxamide (4.6 g) as a yellow solid. MS [M+H] + :426.0.

[0168] Intermediate D1 tert-butyl(3S)-3-[2-[4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazin-1-yl]-2-oxo-ethyl]pyrrolidine-1-carboxylate A mixture of 5-bromo-N-[3-chloro-4-(piperazine-1-carbonyl)phenyl]-1-methylimidazole-2-carboxamide (3 g, 7.03 mmol), 2-[(3S)-1-tert-butoxycarbonylpyrrolidine-3-yl]acetic acid (2.42 g, 10.55 mmol), HATU (4.01 g, 10.55 mmol), and DIPEA (2.73 g, 21.1 mmol) in DMF (15 ml) was stirred at room temperature for 16 hours. The mixture was poured into water. The aqueous layer was extracted with DCM. The combined organic layers were washed with water, dried over anhydrous sodium 2SO4, and concentrated under vacuum to obtain tert-butyl(3S)-3-[2-[4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazin-1-yl]-2-oxo-ethyl]pyrrolidine-1-carboxylate (3.5 g). MS [M+H] + :636.9.

[0169] The following intermediates were prepared in the same manner as intermediate D1. [Table 3]

[0170] Intermediate E1 tert-butyl 5-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate At room temperature, a mixture of 5-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (240 mg, 919 μmol), tert-butoxycarbonyl tert-butyl carbonate (301 mg, 1.38 mmol), DMAP (112 mg, 919 μmol), and Et3N (279 mg, 2.76 mmol) in DCM (10 ml) was stirred for 16 hours. The mixture was then washed with 1N HCl, aqueous NaHCO3, and aqueous NaCl. The organic layer was then dried over anhydrous Na2SO4 and concentrated under vacuum to obtain tert-butyl 5-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate (300 mg).

[0171] The following intermediates were prepared in the same manner as intermediate E1. [Table 4]

[0172] Intermediate E4 tert-butyl 7-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate Step 1: tert-butyl 4-bromo-7-methoxyindole-1-carboxylate At room temperature, a mixture of 4-bromo-7-methoxy-1H-indole (1 g, 4.42 mmol), tert-butoxycarbonyl tert-butyl carbonate (1.16 g, 5.31 mmol), DMAP (54 mg, 442 μmol), and Et3N (895 mg, 1.23 ml, 8.85 mmol) in DCM (10 ml) was stirred for 16 hours. The mixture was then washed with water, dried over anhydrous Na2SO4, and concentrated under vacuum to obtain the crude product. The residue was purified by flash column chromatography to obtain tert-butyl 4-bromo-7-methoxyindole-1-carboxylate (1.2 g) as a yellow oil. MS [M+H] + :325.4.

[0173] Step 2: tert-butyl 7-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate Under N2 protection, a mixture of 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolan (405 mg, 1.59 mmol), tert-butyl 4-bromo-7-methoxyindole-1-carboxylate (400 mg, 1.23 mmol), potassium acetate (361 mg, 3.68 mmol), and 1,1-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex in 1,4-dioxane (20 ml) (100 mg, 123 μmol) was stirred at 70°C for 4 hours. The mixture was then concentrated, and PE was added. The black mixture was filtered. The filtrate was concentrated under vacuum to obtain crude tert-butyl 7-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate. MS [M+H] + :374.0.

[0174] Intermediate E5 tert-butyl 5-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate Step 1: tert-butyl 5-amino-4-bromo-indole-1-carboxylate To a solution of tert-butyl 5-amino-1H-indole-1-carboxylate (2 g, 8.61 mmol) in acetonitrile (30 mL), NBS (1.53 g, 8.61 mmol) was added, and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under vacuum. The residue was purified by column chromatography to obtain tert-butyl 5-amino-4-bromo-1H-indole-1-carboxylate (2.2 g). MS [M+H] + :311.0.

[0175] Step 2: tert-butyl 4-bromo-5-chloroindole-1-carboxylate To a solution of tert-butyl nitrite (298 mg, 2.89 mmol) and copper(II) chloride dihydrate (493 mg, 2.89 mmol) in MeCN (10 mL), add a solution of tert-butyl 5-amino-4-bromo-1H-indole-1-carboxylate (600 mg, 1.93 mmol) in MeCN (5 mL). o Added with C. The reaction mixture was slowly mixed at 80°C. o The mixture was heated to 1°C and stirred for 2 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain tert-butyl 4-bromo-5-chloro-1H-indole-1-carboxylate (368 mg, 1.11 mmol). MS [M+H] + :330.0

[0176] Step 3: tert-butyl 5-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate To a solution of tert-butyl 4-bromo-5-chloro-1H-indole-1-carboxylate (300 mg, 907 μmol) in dioxane (10 mL), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (253 mg, 998 μmol), potassium acetate (178 mg, 1.81 mmol), and 1,1-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (74.1 mg, 90.7 μmol) were added, and the reaction mixture was heated under an argon atmosphere for 80°C. o The mixture was stirred in 1C for 12 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under vacuum. The residue was purified by column chromatography to obtain tert-butyl 5-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (232 mg). MS [M+H] + :378.2.

[0177] Intermediate E6 1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole Step 1: 4-bromo-1-methyl-indole To a solution of 4-bromo-1H-indole (1g, 5.1 mmol) in DMF (15 mL), add sodium hydride (408 mg, 10.2 mmol) in a divided portion. o The reaction mixture was added with C, stirred for 30 minutes, and then methyl iodide (1.45 g, 638 μl, 10.2 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with aqueous ammonia chloride and extracted with EtOAC. The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography to obtain 4-bromo-1-methyl-indole (1 g). MS [M+H] + :210.0.

[0178] Step 2: 1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole To a solution of 4-bromo-1-methyl-1H-indole (1000 mg, 4.76 mmol) in dioxane (10 mL), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (1.33 g, 5.24 mmol), potassium acetate (934 mg, 9.52 mmol), and 1,1-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (389 mg, 476 μmol) were added, and the reaction mixture was reacted under an argon atmosphere for 80°C. o The mixture was stirred in 1C for 12 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under vacuum. The residue was purified by column chromatography to obtain 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (1 g). MS [M+H] + :258.2.

[0179] Intermediate F1 2,3,6-trifluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine In a 25 mL microwave tube, 15 mL of 1,4-dioxane was mixed with 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolan (667 mg, 2.63 mmol), 3-chloro-2,5,6-trifluoropyridine (400 mg, 2.39 mmol), tris(dibenzylideneacetone)dipalladium (219 mg, 239 μmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (228 mg, 478 μmol), and potassium acetate (703 mg, 7.16 mmol). The vial was capped and heated at 100 °C for 3 hours under N2 protection. The reaction mixture was cooled to room temperature and concentrated. The residue was used directly in the next step without further purification.

[0180] Intermediate F2 N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)pyridine-2-amine Step 1: 5-Chloro-N,N-dimethyl-6-(trifluoromethyl)pyridine-2-amine 500 mg (2.31 mmol) of 3,6-dichloro-2-(trifluoromethyl)pyridine and dimethylamine (in methanol) (4.63 mL, 9.26 mmol) were added to a 25 mL microwave vial in 10 mL of MeOH. The vial was capped and heated in a microwave at 100°C for 3 hours. The crude reaction mixture was concentrated under vacuum. The crude material was purified by flash chromatography. 369 mg of 5-chloro-N,N-dimethyl-6-(trifluoromethyl)pyridine-2-amine was obtained. MS [M+H] + :225.0.

[0181] Step 2: N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)pyridine-2-amine 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolan (452 ​​mg, 1.78 mmol), 5-chloro-N,N-dimethyl-6-(trifluoromethyl)pyridine-2-amine (200 mg, 890 μmol), chloro[(di(1-adamantyl)-N-butylphosphine)-2-(2-aminobiphenyl)]palladium(II) (59.5 mg, 89 μmol), and potassium acetate (262 mg, 2.67 mmol) were added to a 5 mL microwave vial in DMSO (5 mL). The vial was capped and heated under N2 at 110 °C for 3 hours. The reaction mixture was poured into 50 mL of H2O and extracted with ethyl acetate (3 × 25 mL). The organic layers were combined, washed with saturated NaCl (1 × 50 mL), dried over Na₂SO₄, and concentrated under vacuum. The crude material was purified by flash chromatography to obtain N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)pyridine-2-amine (89 mg, 282 μmol, yield 31.6%). MS [M+H] + :316.6.

[0182] Intermediate F3 N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidine-2-amine Step 1: N,N-dimethyl-4-(trifluoromethyl)pyrimidine-2-amine To a solution of 2-chloro-4-(trifluoromethyl)pyrimidine (1 g, 5.48 mmol) in MeOH (5 mL), dimethylamine (in methanol) (13.7 mL, 27.4 mmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with brine and extracted with DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum to obtain N,N-dimethyl-4-(trifluoromethyl)pyrimidine-2-amine (0.96 g). MS [M+H] + :192.1.

[0183] Step 2: 5-Bromo-N,N-dimethyl-4-(trifluoromethyl)pyrimidine-2-amine To a solution of N,N-dimethyl-4-(trifluoromethyl)pyrimidine-2-amine (1 g, 5.23 mmol) in AcOH (10 mL), potassium acetate (1.54 g, 15.7 mmol) and bromine (836 mg, 270 μL, 5.23 mmol) were added, and the reaction mixture was prepared at 80°C. o The mixture was stirred in 1C for 20 hours. The reaction mixture was cooled to room temperature, washed with brine, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium 2SO4 and concentrated under vacuum to obtain 5-bromo-N,N-dimethyl-4-(trifluoromethyl)pyrimidine-2-amine (1.03 g). MS [M+H] + :270.0.

[0184] Step 3: N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidine-2-amine To a solution of 5-bromo-N,N-dimethyl-4-(trifluoromethyl)pyrimidine-2-amine (600 mg, 2.22 mmol) in dioxane (10 mL), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (621 mg, 2.44 mmol), potassium acetate (436 mg, 4.44 mmol), and 1,1-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (181 mg, 222 μmol) were added, and the reaction mixture was carried out under an argon atmosphere for 80°C. o The mixture was stirred in 1C for 12 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under vacuum. The residue was purified by column chromatography to obtain N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidine-2-amine (430 mg). MS [M+H] + :318.2.

[0185] Intermediate F4 2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidine Step 1: 2-Methoxy-4-(trifluoromethyl)pyrimidine A solution of 2-chloro-4-(trifluoromethyl)pyrimidine (1.5 g, 8.22 mmol) in anhydrous MeOH (3 mL) was mixed with sodium methoxide (3.29 mL, 16.4 mmol), and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with brine and extracted with DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum to obtain 2-methoxy-4-(trifluoromethyl)pyrimidine (1.4 g). MS [M+H] + :179.0.

[0186] Step 2: 5-Bromo-2-methoxy-4-(trifluoromethyl)pyrimidine To a solution of 2-methoxy-4-(trifluoromethyl)pyrimidine (1.5 g, 8.42 mmol) in AcOH (40 mL), potassium acetate (2.48 g, 25.3 mmol) and bromine (1.35 g, 434 μL, 8.42 mmol) were added, and the reaction mixture was prepared at 80°C. o The mixture was stirred in 1C for 2 hours. The reaction mixture was cooled to room temperature, washed with brine, and extracted in ethyl acetate. The organic layer was dried over anhydrous sodium 2SO4 and concentrated under vacuum. The residue was purified by column chromatography to obtain 5-bromo-2-methoxy-4-(trifluoromethyl)pyrimidine (1 g). MS [M+H] + :257.0.

[0187] Step 3: 2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidine To a solution of 5-bromo-2-methoxy-4-(trifluoromethyl)pyrimidine (300 mg, 1.17 mmol) in dioxane (10 mL), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (326 mg, 1.28 mmol), potassium acetate (229 mg, 2.33 mmol), and 1,1-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (95.3 mg, 117 μmol) were added, and the reaction mixture was incubated under an argon atmosphere for 80°C. o The mixture was stirred in 1C for 12 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under vacuum. The residue was purified by column chromatography to obtain 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidine (256 mg). MS [M+H] + :305.1.

[0188] Intermediate F5 4-Chloro-2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine To a solution of 5-bromo-4-chloro-2-methoxypyridine (1100 mg, 5.0 mmol) in DMSO (10 mL), bis(pinacolato)diborone (1270 mg, 5.0 mmol), Pd(dppf)Cl2 (413 mg, 0.5 mmol), and potassium acetate (980 mg, 10 mmol) were added. The resulting mixture was then degassed with nitrogen for 5 minutes and stirred at 80°C for 4.0 hours.

[0189] After cooling to room temperature, the mixture was poured into water (100 mL), and the aqueous solution was extracted with dimethyl ammonium compound (100 mL x 2). The organic layers were combined, washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a red oily substance. This was purified by flash chromatography to obtain 4-chloro-2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine as a grayish-white solid (400 mg). MS [M+H] + :270.2

[0190] The following intermediates were prepared in the same manner as intermediate F5. [Table 5] Intermediate O1 tert-butyl 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoate

[0191] Step 1: tert-butyl 2-chloro-4-[[1-methyl-5-(2,5,6-trifluoro-3-pyridyl)imidazole-2-carbonyl]amino]benzoate Under N2 protection, a mixture of tert-butyl 4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoate (2.4 g, 5.79 mmol), 2,3,6-trifluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.5 g, 5.79 mmol), Na2CO3 (1.84 g, 17.37 mmol), and 1,1'-bis(di-tert-butylphosphino)ferrocenepalladium dichloride (377.41 mg, 0.579 mmol) in a 25 mL microwave tube was heated at 100°C for 2 hours. The mixture was then filtered and concentrated. The residue was purified by flash column to obtain tert-butyl 2-chloro-4-[[1-methyl-5-(2,5,6-trifluoro-3-pyridyl)imidazole-2-carbonyl]amino]benzoate (2.1 g) as a yellow solid. MS [M+H] + :467.2.

[0192] Step 2: tert-butyl 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoate 2.1 g, 4.5 mmol of tert-butyl 2-chloro-4-[[1-methyl-5-(2,5,6-trifluoro-3-pyridyl)imidazole-2-carbonyl]amino]benzoate was dissolved in 40 mL of MeOH at room temperature. Then, 20.02 g, 44.98 mmol of 2 M dimethylamine in methanol was added. The yellow solution was stirred at room temperature for 1 hour. The mixture was then filtered and dried under vacuum to obtain 1.3 g of tert-butyl 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoate as a yellow solid. MS [M+H] + :492.4.

[0193] The following intermediates were prepared in the same manner as intermediate O1. [Table 6]

[0194] Intermediate H1 2-Chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoic acid [ka] 1.3 g, 2.64 mmol of tert-butyl 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoate was dissolved in 20 mL of dichloromethane and 10 mL of TFA at room temperature. The solution was then stirred for 1 hour. The mixture was concentrated under vacuum to obtain 1 g of 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoic acid as a yellow solid. MS [M+H] + :436.2.

[0195] Intermediate I1 N-[3-chloro-4-(piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide tert-butyl 4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]piperazine-1-carboxylate (600 mg, 0.993 mmol) was dissolved in dichloromethane (9 mL) and TFA (5 mL) at room temperature. The solution was then stirred for 1 hour. The mixture was then concentrated under vacuum, and the residue was dissolved in DCM. The solution was basicized with NH3.H2O. The aqueous layer was extracted with DCM. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under vacuum to obtain N-[3-chloro-4-(piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carboxamide (450 mg). MS [M+H] + :504.1.

[0196] The following intermediates were prepared in the same manner as intermediate I1. [Table 7]

[0197] Intermediate J1 N-[3-chloro-4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide DMF (5 mL) contains N-[3-chloro-4-(piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide (400 mg, 0.794 mmol), 2-(dimethylamino)acetic acid (122.78 mg, 1.19 mmol), HATU (603.63 mg, 1.59 mmol), and DIPEA (30 A mixture of 7.77 mg and 2.38 mmol was stirred at room temperature for 3 hours. The mixture was then poured into water. The aqueous layer was extracted with DCM. The organic layer was concentrated to obtain the crude product N-[3-chloro-4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide. MS [M+H] + :589.3.

[0198] The following intermediates were prepared in the same manner as intermediate J1. [Table 8-1] [Table 8-2] [Table 8-3] [Table 8-4]

[0199] Intermediate K1 N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide Step 1: tert-butyl N-[6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]hexyl]carbamate A mixture of 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoic acid (400 mg, 0.918 mmol), tert-butyl N-(6-aminohexyl)carbamate (297.82 mg, 1.38 mmol), HATU (697.98 mg, 1.84 mmol), and DIPEA (355.88 mg, 2.75 mmol) in DMF (6 mL) was stirred at room temperature for 3 hours. The mixture was then poured into water. The aqueous layer was extracted with DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum to obtain the crude product tert-butyl N-[6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]hexyl]carbamate. MS [M+H] + :634.2.

[0200] Step 2: N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide tert-butyl N-[6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]hexyl]carbamate (500 mg, 0.788 mmol) was dissolved in dichloromethane (10 mL) and TFA (5 mL) at room temperature. The solution was then stirred for 1 hour. The mixture was concentrated and water was added. The mixture was basicized with DIPEA. The aqueous layer was extracted with DCM. The combined organic layers were washed with water, dried over anhydrous Na2SO4, and concentrated under vacuum to obtain the crude product N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carboxamide. MS [M+H] + :534.3.

[0201] Intermediate L1 N-[3-chloro-4-(4-piperidylcarbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide Step 1: tert-butyl 4-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]piperidine-1-carboxylate 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoic acid (intermediate H1, 240 mg, 0.551 mmol), 1-methylimidazole (158.24 mg, 153.63 μL, 1.93 mmol), and 4-aminopiperidine-1-carboxylic acid tert-butyl ester (132.35 mg, 0.661 mmol) were dissolved in acetonitrile (6 mL), and chloro-n,n,n',n'-tetramethylformamidinium hexafluorophosphate (185.42 mg, 0.661 mmol) was added all at once. The mixture was stirred at room temperature for 1 hour. The solvent was removed under vacuum. The residue was purified by flash chromatography to obtain the crude product tert-butyl 4-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]piperidine-1-carboxylate. MS [M+H] + :618.4.

[0202] Step 2: N-[3-chloro-4-(4-piperidylcarbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide tert-butyl 4-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]piperidine-1-carboxylate (320 mg, 0.518 mmol) was stirred at room temperature for 2 hours in dichloromethane (4 mL) and 1 mL of TFA. The solvent was removed under vacuum to obtain the crude product, which was used in the next step without purification. MS [M+H] + :518.1.

[0203] The following intermediates were prepared in the same manner as intermediate L1. [Table 9]

[0204] Intermediate L4 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperidine-4-carboxylic acid Step 1: Methyl 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperidine-4-carboxylate To a solution of 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoic acid (300 mg, 0.688 mmol) in N,N-dimethylformamide (3 mL), methyl isonipecoate (98.56 mg, 92.98 μL, 0.688 mmol), o-(7-aza-1h-benzotriazol-1-yl)-n,n,n',n'-tetramethyluronium hexafluorophosphate (392.61 mg, 1.03 mmol) and TEA (139.32 mg, 1.376 mmol) were added, and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water and filtered. The filtered cake was dried in vacuum to obtain methyl 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperidine-4-carboxylate (320 mg). MS [M+H] + :561.2

[0205] Step 2: 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperidine-4-carboxylic acid The reaction mixture was stirred at room temperature for 2 hours in a solution of 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]isopiperidin-4-carboxylic acid (230 mg) in a mixed solvent of methanol (5 mL) and water (1 mL). The reaction mixture was acidified with acetic acid. The mixture was poured into water and filtered. The filtered cake was dried under vacuum to obtain 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]piperidine-4-carboxylic acid (230 mg). MS [M+H] + :547.2

[0206] Intermediate M1 N-[4-[[1-[3-(2-aminoethoxy)propanoyl]-4-piperidyl]carbamoyl]-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide 200 mg of tert-butyl N-[2-[3-[4-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]-1-piperidyl]-3-oxopropoxy]ethyl]carbamate was dissolved in 4 M HCl / 1,4-dioxane (5 mL) and stirred at room temperature for 2 hours. The solvent was removed under vacuum to obtain the crude product, which was purified by preparative HPLC. MS [M+H] + :633.2.

[0207] The following intermediates were prepared in the same manner as intermediate M1. [Table 10-1] [Table 10-2]

[0208] Example A1 N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(5-fluoro-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; formic acid [ka] Step 1: tert-butyl4-[2-[[4-[4-[2-[(3S)-1-tert-butoxycarbonylpyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]-3-chlorophenyl]carbamoyl]-3-methylimidazole-4-yl]-5-fluoroindole-1-carboxylate 1,4-Dioxane (10 mL) and water (1 mL) contain tert-butyl(3S)-3-[2-[4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazin-1-yl]-2-oxo-ethyl]pyrrolidine-1-carboxylate (400 mg, 627 μmol), tert-butyl5-fluoro-4-(4,4,5,5-teto A mixture of lamethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate (272 mg, 752 μmol), Na2CO3 (199 mg, 1.88 mmol), and 1,1'-bis(di-tert-butylphosphino)ferrocenepalladium dichloride (40.86 mg, 0.063 mmol) was heated in a 25 mL microwave tube at 110°C for 50 minutes under N2 protection. The mixture was then filtered, and the filtrate was concentrated. The residue was dissolved in DCM. The organic layer was washed with water, dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by flash column chromatography to obtain tert-butyl4-[2-[[4-[4-[2-[(3S)-1-tert-butoxycarbonylpyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]-3-chlorophenyl]carbamoyl]-3-methylimidazole-4-yl]-5-fluoroindole-1-carboxylate.

[0209] Step 2: N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(5-fluoro-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; formic acid A solution of tert-butyl 4-[2-[[4-[4-[2-[(3S)-1-tert-butoxycarbonylpyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]-3-chlorophenyl]carbamoyl]-3-methylimidazole-4-yl]-5-fluoroindole-1-carboxylate (400 mg, 0.505 mmol) in DCM (10 mL) and TFA (6 mL) was stirred at room temperature for 30 minutes. The solution was then concentrated and basicized with NH3.H2O. The aqueous layer was extracted with DCM. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under vacuum to obtain the crude product. The residue was purified by preparative HPLC to obtain N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(5-fluoro-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; formic acid (31 mg). MS [M+H] + :592.3.

[0210] The following intermediates were prepared in the same manner as in Example A1. [Table 11-1] [Table 11-2] [Table 11-3] [Table 11-4] [Table 11-5]

[0211] Example B1 N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; formic acid [ka] Step 1: tert-butyl N-[6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]hexyl]carbamate A mixture of 2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoic acid (400 mg, 0.918 mmol), tert-butyl N-(6-aminohexyl)carbamate (297.82 mg, 1.38 mmol), HATU (697.98 mg, 1.84 mmol), and DIPEA (355.88 mg, 2.75 mmol) in DMF (6 mL) was stirred at room temperature for 3 hours. The mixture was then poured into water. The aqueous layer was extracted with DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum to obtain the crude product tert-butyl N-[6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]hexyl]carbamate. MS [M+H] + :634.2.

[0212] Step 2: N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; formic acid tert-butyl N-[6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]amino]hexyl]carbamate (500 mg, 0.788 mmol) was dissolved in dichloromethane (10 mL) and TFA (5 mL) at room temperature. The solution was then stirred for 1 hour. The mixture was concentrated and water was added. The mixture was basicized with DIPEA. The aqueous layer was extracted with DCM. The combined organic layers were washed with water, dried over anhydrous Na2SO4, and concentrated under vacuum to obtain the crude product. The residue was purified by preparative HPLC to obtain N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carboxamide; formic acid. MS [M+H] + :534.3.

[0213] Example C1 N-[3-chloro-4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; formic acid [ka] DMF (5 mL) contains N-[3-chloro-4-(piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide (400 mg, 0.794 mmol), 2-(dimethylamino)acetic acid (122.78 mg, 1.19 mmol), HATU (603.63 mg, 1.59 mmol), and DIPEA (307.77 mg, 2 A mixture of 0.38 mmol was stirred at room temperature for 3 hours. The mixture was then poured into water. The aqueous layer was extracted by DCM. The organic layer was concentrated, and the residue was purified by preparative HPLC to obtain N-[3-chloro-4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; formic acid. MS [M+H] + :589.3.

[0214] The following intermediates were prepared in the same manner as in Example C1. [Table 12]

[0215] Example D1 [2-[4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperazine-1-yl]-2-oxoethyl]-trimethylammonium; formate [ka] At room temperature, a mixture of N-[3-chloro-4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carboxamide (200 mg, 0.340 mmol), iodomethane (481.94 mg, 3.4 mM), and DIPEA (438.82 mg, 3.4 mmol) in acetonitrile (5 mL) was stirred for 3 hours. The mixture was then concentrated, and the residue was purified by preparative HPLC to obtain [2-[4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]piperazine-1-yl]-2-oxoethyl]-trimethylammonium; formic acid. MS [M+H] + :603.3.

[0216] The following intermediates were prepared in the same manner as in Example D1. [Table 13-1] [Table 13-2] [Table 13-3]

[0217] Example E1 N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methylimidazole-2-carboxamide; formate [ka] Step 1: tert-butyl 4-[4-[2-chloro-4-[[1-methyl-5-(2,5,6-trifluoro-3-pyridyl)imidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate In a 25 mL microwave vial, tert-butyl 4-[4-[4-[(5-bromo-1-methylimidazole-2-carbonyl)amino]-2-chlorobenzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate (500 mg, 784 μmol), 2,3,6-trifluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (223 mg, 861 μmol), Na2CO3 (249 mg, 2.35 mmol), and 1,1'-bis(di-tert-butylphosphin)ferrocenepalladium dichloride (46.7 mg, 78.4 μmol) were added in dioxane (10 mL) / water (1 mL). The vial was sealed and heated in a microwave under N2 at 100 °C for 2 hours. The crude reaction mixture was concentrated under vacuum. The crude substance was purified by flash chromatography to obtain tert-butyl4-[4-[2-chloro-4-[[1-methyl-5-(2,5,6trifluoro-3-pyridyl)imidazole-2-carbonyl]amino]benzoyl] [M-boc] piperazine-1-carbonyl piperidine-1-carboxylate (275 mg) was obtained. + :590.2.

[0218] Step 2: tert-butyl4-[4-[2-chloro-4-[[5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate In a 100 mL round-bottom flask, tert-butyl 4-[4-[2-chloro-4-[[1-methyl-5-(2,5,6-trifluoro-3-pyridyl)imidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate (91 mg, 132 μmol) was combined with MeOH (5 mL) to obtain a pale brown solution. Methaneamine (659 μl, 1.32 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour. The crude reaction mixture was concentrated under vacuum. The reaction mixture was used directly in the next step to obtain tert-butyl 4-[4-[2-chloro-4-[[5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate (92.5 mg). MS [M+H] + :701.6.

[0219] Step 3: N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methylimidazole-2-carboxamide; formate In a 100 mL round-bottom flask, tert-butyl 4-[4-[2-chloro-4-[[5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methyl-imidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate (92.45 mg, 132 μmol) was combined with THF (4 mL) to obtain a pale brown solution. HCl (in water) (1.1 ml, 13.2 mmol) was added. The reaction mixture was stirred at room temperature for 30 minutes. The crude reaction mixture was concentrated under vacuum. The crude substance was purified by preparative HPLC to obtain N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methylimidazole-2-carboxamide formate (19 mg). MS [M+H] + :601.3.

[0220] The following intermediates were prepared in the same manner as in Example E1. [Table 14]

[0221] Example F1 N-[3-chloro-4-[4-(4-hydroxypiperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; formic acid [ka] In a 100 mL round-bottom flask, tert-butyl 4-[4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]-4-hydroxy-piperidine-1-carboxylate (110 mg, 150 μmol) was combined with THF (3 mL) to obtain a pale brown solution. HCl (in water) (1.25 ml, 15 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour. The crude reaction mixture was concentrated under vacuum. The crude substance was purified by preparative HPLC to obtain N-[3-chloro-4-[4-(4-hydroxypiperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; formic acid (25 mg). MS [M+H] + :631.1.

[0222] The following intermediates were prepared in the same manner as in Example F1. [Table 15-1] [Table 15-2] [Table 15-3]

[0223] Assay procedure Antimicrobial susceptibility testing: Determination of the 90% growth inhibitory concentration (IC90) The in vitro antibacterial activity of the compound was determined according to the following procedure: The assay quantitatively measured the in vitro activity of the compound against Acinetobacter baumannii ATCC17961 using 10-point Iso-Sensitest broth medium.

[0224] The stock compound in DMSO was progressively diluted twofold in a 384-well microtiter plate (e.g., in the range of final concentrations from 50 to 0.097 μM), and 49 μl of bacterial suspension in Iso-Sensitest medium was inoculated to a final volume of 50 μl / well, resulting in approximately 5 x 10⁴ (5) The final cell concentration was set to CFU / ml. Microtiter plates were incubated at 35±2°C.

[0225] Bacterial cell growth was determined by measuring optical density at λ=600nm every 20 minutes over a 16-hour period. Growth inhibition was calculated during the logarithmic growth of bacterial cells, and the concentrations that inhibited growth by 50% (IC50) and 90% (IC90) were determined.

[0226] Table 1 shows the 90% growth inhibitory concentration (IC90) of the compound of the present invention obtained in micromoles per liter against the Acinetobacter baumannii ATCC17961 strain.

[0227] The specific compound of the present invention exhibits an IC90 (Acinetobacter baumannii ATCC17961) ≤ 25 μmol / L.

[0228] A more specific compound of the present invention exhibits an IC90 (Acinetobacter baumannii ATCC17961) ≤ 5 μmol / L.

[0229] The most specific compound of the present invention exhibits an IC90 (Acinetobacter baumannii ATCC17961) ≤ 1 μmol / L. [Table 16]

[0230] Example 1 The compound of formula (I) can be used as an active ingredient in a manner known to itself to manufacture tablets of the following composition: per tablet Active ingredient 200mg Microcrystalline cellulose 155mg Corn starch 25mg Talc 25mg Hydroxypropyl methylcellulose 20 mg 425mg

[0231] Example 2 The compound of formula (I) can be used as an active ingredient in a manner known to itself to produce capsules of the following composition. per capsule Active ingredient: 100.0 mg Corn starch 20.0 mg Lactose 95.0 mg Talc 4.5mg Magnesium stearate 0.5 mg 220.0 mg

[0232] Example 3 The compound of formula (I) can be used in known ways as an active ingredient for the preparation of intravenous solutions of the following compositions. Active ingredient 100mg Lactic acid 90% 100mg Add an appropriate amount of NaOH or HCl to adjust the pH to 4.0. To adjust the osmotic pressure to 290 mOsm / kg, add an appropriate amount of sodium chloride or glucose. Prepare by adding 100 ml of sterile water for injection (WFI).

[0233] Example 4 The compound of formula (I) can be used in known ways as an active ingredient for the preparation of intravenous solutions of the following compositions. Active ingredient 100mg Hydroxypropyl-beta-cyclodextrin 10g Add an appropriate amount of NaOH or HCl to adjust the pH to 7.4. To adjust the osmotic pressure to 290 mOsm / kg, add an appropriate amount of sodium chloride or glucose. Make 100ml of water for injection (WFI)

Claims

1. Equation (I) 【Chemistry 1】 (In the formula, R １ teeth, (i) base 【Chemistry 2】 (ii) group 【Transformation 3】 and (iii) group 【Chemistry 4】 Selected from, R ２ is selected from hydrogen, halogen, cyano, C １ to C ６ alkyl, C １ to C ６ alkoxy, halo-C １ to C ６ alkyl, and halo-C １ to C ６ alkoxy, and is selected from R ３ C １ ~C ６ Alkyl and Halo-C １ ~C ６ Selected from alkyl groups, R ４ , R ５ , and R ６ These are, independently, hydrogen, halogen, cyano, hydroxyl, and C. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkoxy, amino, C １ ~C ６ Alkyl-NH- and (C １ ~C ６ Alkyl) ２ Selected from N-, R ７ is hydroxy-C １ ~C ６ Alkyl, amino-C １ ~C ６ Alkyl, C １ ~C ６ Alkyl-NH-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkyl-, amino-C １ ~C ６ Alkoxy-C １ ~C ６ Alkyl, C １ ~C ６ Alkyl-NH-C １ ~C ６ Alkoxy-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkoxy-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkoxy-C １ ~C ６ Alkyl and group 【Transformation 5】 Selected from, R ８ is hydroxy-C １ -C ６ alkyl, amino-C １ -C ６ alkyl, C １ -C ６ alkyl-NH-C １ -C ６ alkyl-, (C １ -C ６ alkyl) ２ N-C １ -C ６ alkyl-, (C １ -C ６ alkyl) ３ N ＋ -C １ -C ６ alkyl, amino-C １ -C ６ alkoxy-C １ -C ６ alkyl, C １ -C ６ alkyl-NH-C １ -C ６ alkoxy-C １ -C ６ alkyl-, (C １ -C ６ alkyl) ２ N-C １ -C ６ alkoxy-C １ -C ６ alkyl-, (C １ -C ６ alkyl) ３ N ＋ -C １ -C ６ alkoxy-C １ -C ６ alkyl, and the group 【Transformation 6】 Selected from, R ９ and R １１ These are, independently, hydrogen and C １ ~C ６ Selected from alkyl groups, R １０ is hydrogen, C １ ~C ６ Alkyl, hydroxy-C １ ~C ６ Alkyl, amino-C １ ~C ６ Alkyl-, C １ ~C ６ Alkyl-NH-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkyl-, and (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Selected from alkyl-, R １２ , R １３ , R １４ , R １５ , R １６ , and R １７ These are, independently, hydrogen, halogen, cyano, hydroxyl, amino, and C. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkoxy, hydroxy-C １ ~C ６ Alkyl, amino-C １ ~C ６ Alkyl, C １ ~C ６ Alkyl-NH-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkyl-, and (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Selected from alkyl-, A is a 5- to 14-membered heteroaryl compound. B and C are independently 3- to 14-membered heterocycloalkyl and C ３ ~C １０ Selected from cycloalkyl groups, X １ , X ２ , and Y are independently selected from N and CH, m, n, p, and q are each independently either 0 or 1. L １ and L ２ These are, independently, carbonyl, -C(O)-C １ ~C ６ Alkyl, -C １ ~C ６ Selected from alkyl-C(O)-, -NH-C(O)-, and -C(O)-NH-, However, A is not a pyrazole. Compounds thereof, or pharmaceutically acceptable salts thereof.

2. R １ but, (i) base 【Transformation 7】 (ii) group 【Transformation 8】 and (iii) group 【Chemistry 9】 Selected from, R ７ However, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkyl-, and group 【Chemistry 10】 Selected from, R ８ However, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkoxy-C １ ~C ６ Alkyl and group 【Chemistry 11】 Selected from, R ９ and R １１ However, both are hydrogen, R １０ However, Amino-C １ ~C ６ Alkyl and (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Selected from alkyl-, R １２ However, hydrogen, hydroxy, amino-C １ ~C ６ Alkyl and (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Selected from alkyl-, R １３ , R １４ , R １６ , and R １７ However, each independently, hydrogen and C １ ~C ６ Selected from alkyl groups, R １５ However, it is hydroxyl, B is a 3- to 14-membered heterocycloalkyl and C ３ ~C １０ Selected from cycloalkyl groups, C is a 3- to 14-membered heterocycloalkyl group. L １ However, carbonyl, -C １ ~C ６ Selected from alkyl-C(O)-, -NH-C(O)-, and -C(O)-NH-, L ２ However, it is selected from carbonyl and -C(O)-NH-, X １ and X ２ However, each is independently selected from N and CH, Y is N, m and n are both 1, p and q are both 0, or p and q are both 1. A compound of formula (I) as described in claim 1, or a pharmaceutically acceptable salt thereof.

3. R １ However, 【Chemistry 12】 And, R ７ However, 【Chemistry 13】 And, R １２ However, it is hydrogen or hydroxyl, R １３ and R １４ However, both are hydrogen, B is a 3- to 14-membered heterocycloalkyl, L １ However, carbonyl or -C １ ~C ６ It is alkyl-C(O)-, X １ And Y are both N, m and n are both 1. A compound of formula (I) as described in claim 2, or a pharmaceutically acceptable salt thereof.

4. R １ However, 【Chemistry 14】 And, R ７ However, 【Chemistry 15】 And, R １２ However, it is hydrogen or hydroxyl, R １３ and R １４ However, both are hydrogen, B is piperidine or pyrrolidine, L １ However, carbonyl or -CH ２ -C(O)-, X １ And Y are both N, m and n are both 1. A compound of formula (I) as described in claim 3, or a pharmaceutically acceptable salt thereof.

5. R ２ However, halogen or C １ ~C ６ A compound of formula (I) according to any one of claims 1 to 4, which is alkyl, or a pharmaceutically acceptable salt thereof.

6. R ２ A compound of formula (I) according to claim 5, or a pharmaceutically acceptable salt thereof, wherein is a halogen.

7. R ２ A compound of formula (I) according to claim 6, or a pharmaceutically acceptable salt thereof, wherein is chloro.

8. R ３ However, C １ ~C ６ A compound of formula (I) according to any one of claims 1 to 7, which is alkyl, or a pharmaceutically acceptable salt thereof.

9. R ３ A compound of formula (I) according to claim 8, or a pharmaceutically acceptable salt thereof, wherein is methyl.

10. R ４ However, hydrogen, halogen, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkyl-NH-, (C １ ~C ６ Alkyl) ２ N- and Halo-C １ ~C ６ Selected from alkyl groups, R ５ However, hydrogen, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halogens, and (C １ ~C ６ Alkyl) ２ Selected from N-, R ６ However, it is hydrogen or halogen. A compound of formula (I) according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof.

11. R ４ However, halogen, (C １ ~C ６ Alkyl) ２ N- and Halo-C １ ~C ６ Selected from alkyl groups, R ５ However, hydrogen, halogens and C １ ~C ６ Selected from alkoxy, R ６ However, it is hydrogen or halogen. A compound of formula (I) according to claim 10, or a pharmaceutically acceptable salt thereof.

12. R ４ However, fluoro(methyl) ２ N-, and CF ３ Selected from, R ５ However, selected from hydrogen, fluoro and methoxy, R ６ However, it is hydrogen or fluoro. A compound of formula (I) according to claim 11, or a pharmaceutically acceptable salt thereof.

13. A compound of formula (I) according to any one of claims 1 to 12, wherein A is a 6- to 14-membered heteroaryl compound, or a pharmaceutically acceptable salt thereof.

14. A compound of formula (I) according to claim 13, or a pharmaceutically acceptable salt thereof, wherein A is a 6- to 9-membered heteroaryl compound.

15. A compound of formula (I) according to claim 11, or a pharmaceutically acceptable salt thereof, wherein A is selected from pyridyl, indolyl, indazolyl, pyrimidinyl, and 2,3-dihydro-1,4-benzodioxynyl.

16. A is a compound of formula (I) according to claim 12, or a pharmaceutically acceptable salt thereof, wherein A is selected from pyridyl, indolyl, and indazolyl.

17. R １ but, (i) base 【Chemistry 16】 (ii) group 【Chemistry 17】 and (iii) group [Chemistry 18] Selected from, R ２ However, halogen or C １ ~C ６ It is alkyl, R ３ However, C １ ~C ６ It is alkyl, R ４ However, hydrogen, halogen, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkyl-NH-, (C １ ~C ６ Alkyl) ２ N- and Halo-C １ ~C ６ Selected from alkyl groups, R ５ However, hydrogen, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halogens, and (C １ ~C ６ Alkyl) ２ Selected from N-, R ６ However, it is hydrogen or halogen, R ７ However, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkyl-, and group 【Chemistry 19】 Selected from, R ８ However, (C １ ~C ６ Alkyl) ２ N-C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkyl-, (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Alkoxy-C １ ~C ６ Alkyl and group 【Chemistry 20】 Selected from, R ９ and R １１ However, both are hydrogen, R １０ However, Amino-C １ ~C ６ Alkyl and (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Selected from alkyl-, R １２ However, hydrogen, hydroxy, amino-C １ ~C ６ Alkyl and (C １ ~C ６ Alkyl) ３ N ＋ -C １ ~C ６ Selected from alkyl-, R １３ , R １４ , R １６ , and R １７ However, each independently, hydrogen and C １ ~C ６ Selected from alkyl groups, R １５ However, it is hydroxyl, A is a 6- to 9-membered heteroaryl compound. B is a 3- to 14-membered heterocycloalkyl and C ３ ~C １０ Selected from cycloalkyl groups, C is a 3- to 14-membered heterocycloalkyl group. L １ However, carbonyl, -C １ ~C ６ Selected from alkyl-C(O)-, -NH-C(O)-, and -C(O)-NH-, L ２ However, it is selected from carbonyl and -C(O)-NH-, X １ and X ２ However, each is independently selected from N and CH, Y is N, m and n are both 1, p and q are both 0, or p and q are both 1. A compound of formula (I) as described in claim 1, or a pharmaceutically acceptable salt thereof.

18. R １ However, 【Chemistry 21】 And, R ２ However, it is a halogen, R ３ However, C １ ~C ６ It is alkyl; R ４ However, halogen, (C １ ~C ６ Alkyl) ２ N- and Halo-C １ ~C ６ Selected from alkyl groups, R ５ However, hydrogen, halogens and C １ ~C ６ Selected from alkoxy, R ６ However, it is hydrogen or halogen, R ７ However, 【Chemistry 22】 And, R １２ However, it is hydrogen or hydroxyl, R １３ and R １４ However, both are hydrogen, A is a 6- to 9-membered heteroaryl compound. B is a 3- to 14-membered heterocycloalkyl, L １ However, carbonyl or -C １ ~C ６ It is alkyl-C(O)-, X １ And Y are both N, m and n are both 1. A compound of formula (I) according to claim 17, or a pharmaceutically acceptable salt thereof.

19. R １ However, 【Chemistry 23】 And, R ２ However, it is Chlor, R ３ However, it is methyl, R ４ However, fluoro(methyl) ２ N-, and CF ３ Selected from, R ５ However, selected from hydrogen, fluoro and methoxy, R ６ However, it is hydrogen or fluoro, R ７ However, 【Chemistry 24】 And, R １２ However, it is hydrogen or hydroxyl, R １３ and R １４ However, both are hydrogen, A is selected from pyridyl, indolyl, and indazolyl. B is piperidine or pyrrolidine, L １ However, carbonyl or -CH ２ -C(O)-, X １ And Y are both N, m and n are both 1. A compound of formula (I) according to claim 18, or a pharmaceutically acceptable salt thereof.

20. The compound of formula (I) above, N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(5-fluoro-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(6-fluoro-3-methyl-1H-indazole-5-yl)-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-1-methyl-5-[3-(trifluoromethyl)-1H-indazole-5-yl]imidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(7-methoxy-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(2,6-dichloro-3-pyridyl)-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(2,6-dimethoxy-3-pyridyl)-1-methylimidazole-2-carboxamide; 5-(5-chloro-2-methoxy-4-pyridyl)-N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[2-(dimethylamino)-4-(trifluoromethyl)pyrimidine-5-yl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2-methoxy-4-(trifluoromethyl)pyrimidine-5-yl]-1-methylimidazole-2-carboxamide; 5-(5-chloro-1H-indole-4-yl)-N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(1H-indole-4-yl)-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methyl-5-(1-methylindole-4-yl)imidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; 5-(4-chloro-6-methoxy-3-pyridyl)-N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[4-[4-[(1R,5S)-3-azabicyclo[3.1.0]hexane-6-carbonyl]piperazine-1-carbonyl]-3-chlorophenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2-(difluoromethyl)-6-methoxy-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-methylimidazole-2-carboxamide; N-[4-(6-aminohexylcarbamoyl)-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[4-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]-3-methylphenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[[3-[[2-(dimethylamino)acetyl]amino]cyclobutyl]carbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[[2-(dimethylamino)acetyl]amino]piperidine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; [2-[4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperazine-1-yl]-2-oxoethyl]trimethylammonium; [2-[4-[4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]-2-methyl-benzoyl]piperazine-1-yl]-2-oxo-ethyl]-trimethyl-ammonium; 6-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]amino]hexyl-trimethylammonium; N-[3-chloro-4-[4-(1,1-dimethylpiperidine-1-ium-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(1,1-dimethylpyrrolidine-1-ium-3-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[(2S,4R)-4-hydroxy-1,1-dimethyl-pyrrolidine-1-ium-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-(1,1-dimethylpiperidine-1-ium-4-yl)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; [2-[[3-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]amino]cyclobutyl]amino]-2-oxo-ethyl]-trimethylammonium; [2-[[1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]-4-piperidyl]amino]-2-oxo-ethyl]-trimethylammonium; 2-[3-[4-[[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]amino]-1-piperidyl]-3-oxopropoxy]ethyl-trimethyl-ammonium; [3-[4-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]piperazine-1-carbonyl]cyclobutyl]methyl-trimethyl-ammonium; N-[3-chloro-4-[[1-[(2S,4R)-4-hydroxy-1,1-dimethylpyrrolidine-1-ium-2-carbonyl]-4-piperidyl]carbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]-N-(1,1-dimethylpyrrolidine-1-ium-3-yl)piperidine-4-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[2,5-difluoro-6-(methylamino)-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2-fluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2-methyl-3-pyridyl]-1-methylimidazole-2-carboxamide; 5-[2-chloro-6-(dimethylamino)-3-pyridyl]-N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(4-hydroxypiperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-(4-hydroxy-4-piperidyl)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(pyrroridine-3-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-(4-piperidyl)acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[4-[4-[3-(aminomethyl)cyclobutanecarbonyl]piperazine-1-carbonyl]-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[4-[[1-[3-(2-aminoethoxy)propanoyl]-4-piperidyl]carbamoyl]-3-chlorophenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[[1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]-4-piperidyl]carbamoyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; and 1-[2-chloro-4-[[5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carbonyl]amino]benzoyl]-N-pyrrolidine-3-ylpiperidine-4-carboxamide A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the above.

21. The compound of formula (I) above, N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-(5-fluoro-1H-indole-4-yl)-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-1-methyl-5-[3-(trifluoromethyl)-1H-indazole-5-yl]imidazole-2-carboxamide; N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]phenyl]-5-[6-methoxy-2-(trifluoromethyl)-3-pyridyl]-1-methylimidazole-2-carboxamide; N-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide; and N-[3-chloro-4-[4-[2-[(3S)-pyrrolidine-3-yl]acetyl]piperazine-1-carbonyl]phenyl]-5-[6-(dimethylamino)-2,5-difluoro-3-pyridyl]-1-methylimidazole-2-carboxamide A compound of formula (I) according to claim 20, or a pharmaceutically acceptable salt thereof, selected from the above.

22. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

23. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof, and a therapeutically inactive carrier.

24. A pharmaceutical composition for use as an antibiotic, comprising a compound of formula (I) according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof.

25. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of hospital-acquired infections and resulting diseases.

26. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of infections caused by Gram-negative bacteria and resulting diseases.

27. The pharmaceutical composition according to claim 26, wherein the Gram-negative bacteria are selected from Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli (E. coli).

28. The pharmaceutical composition according to claim 27, wherein the Gram-negative bacterium is Acinetobacter baumannii.

29. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of infections and resulting diseases caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, Escherichia coli (E. coli), or combinations thereof.

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