Antibacterial 8-phenylamino-3-(pyrazol-4-yl)imidazo[1,2-a]pyrazine derivatives
Novel imidazopyrazine derivatives address the challenge of antibiotic-resistant Acinetobacter baumannii infections by offering effective treatment and prevention strategies.
Patent Information
- Application Number
- JP2022565598
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2021-03-19
- Filing Date
- 2021-04-27
- Publication Date
- 2025-11-17
- Estimated Expiration
- 2041-04-27
AI Technical Summary
There is a high demand for compounds effective against drug-susceptible and drug-resistant strains of Acinetobacter baumannii, a bacterium causing hospital-acquired infections with limited therapeutic options due to increasing antibiotic resistance.
Development of novel imidazopyrazine derivatives, such as compound of formula (I), synthesized through specific coupling and reaction processes, exhibiting antibacterial activity against Acinetobacter baumannii and other Gram-negative bacteria.
The imidazopyrazine derivatives effectively treat or prevent infections caused by Acinetobacter baumannii and other bacteria, providing therapeutic options for multidrug-resistant strains.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to novel imidazopyrazine derivatives that exhibit antibacterial properties. The present invention also relates to methods of using the 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] Acinetobacter baumannii is a Gram-negative, aerobic, non-fermenting bacterium that has been recognized in recent decades as a novel pathogen with very limited therapeutic options.
[0003] Acinetobacter baumannii is considered a serious threat by the US Centers for Disease Control and Prevention and currently causes the majority of hospital-acquired infections, belonging to the so-called "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species and Escherichia coli) that effectively "escape" the activity of antimicrobial agents.
[0004] Acinetobacter baumannii occurs most frequently in intensive care units and surgical wards, where widespread antibiotic use has allowed it to select for resistance to all known antimicrobial agents and can cause infections such as bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections.
[0005] Acinetobacter baumannii has a remarkable ability to upregulate and acquire resistance determinants and exhibits environmental persistence that allows its survival and spread in the hospital environment, making the organism a frequent cause of infectious disease outbreaks and an endemic healthcare-associated pathogen in that environment.
[0006] Due to increasing antibiotic resistance to most, if not all, available therapeutic options, multidrug-resistant (MDR) A. baumannii infections, especially those caused by carbapenem-resistant A. baumannii, are extremely difficult or even impossible to treat and are associated with increased morbidity and length of stay in intensive care units as well as high mortality.
[0007] According to the Antimicrobial Availability Task Force (AATF) of the Infectious Diseases Society of America (IDSA), Acinetobacter baumannii has been and remains considered "a prime example of the mismatch that exists between unmet medical need and the current antibiotic research and development pipeline." Thus, there is a high demand and need to identify compounds suitable for treating diseases and infections caused by Acinetobacter baumannii.
[0008] The present invention provides novel compounds that exhibit activity against drug-susceptible and drug-resistant strains of Acinetobacter baumannii. Summary of the Invention
[0009] In a first aspect, the present invention provides a compound of formula (I): [ka] (I) or a pharmaceutically acceptable salt thereof, wherein X and R 3 ~R 9 is as described herein.
[0010] In one aspect, the present invention provides a method for preparing a compound of formula (I) described herein, comprising: (i) Carboxylic acid IXa (wherein R 3 -R 9 is as defined herein) [ka] (IXa), Amine V (wherein R 1 and R 2 is as defined herein) [ka] (V) and reacting in the presence of a coupling reagent (such as HATU, TBTU, etc.) and a base (such as DIPEA, NEt3, etc.) to form a compound of formula (I) as described above; or (ii) Compound VIa [wherein R 1 ~R 4 , R 8 and R 9 is as defined herein and Z is halogen or triflate. [ka] (VIa), Compound VIIa (wherein R 5 ~R 7 is as defined herein, and Y is a boronic acid or boronic ester. [ka] VIIa, reacting in a solvent (e.g., dioxane, DMF, THF, etc.) in the presence of a transition metal catalyst (e.g., PdCl(dppf)-CHCl adduct, Pd(PPh) and a base (e.g., NEt, DIPEA, carbonate, KPO, NaOtBu, etc.) to form a compound of formula (I).
[0011] In a further aspect, the present invention provides a compound of formula (I) as described herein when prepared according to the process described herein.
[0012] In a further aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.
[0013] In a further aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.
[0014] In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use as an antibiotic.
[0015] In a further aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of hospital-acquired infections and resulting diseases.
[0016] In a further aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of infections and resulting diseases caused by Gram-negative bacteria.
[0017] In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species or Escherichia coli, or combinations thereof.
[0018] In a further aspect, the present invention provides a method 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, or combinations thereof, comprising administering to a mammal a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.
[0019] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, as an antibiotic.
[0020] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli, or combinations thereof.
[0021] In a further aspect, the present invention provides the use of a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament useful for the treatment or prevention of infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli, or a combination thereof. DETAILED DESCRIPTION OF THE INVENTION
[0022] definition It should be understood that any feature, integer, characteristic, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the invention is applicable to any other aspect, embodiment, or example described herein, except where inconsistent therewith. All features disclosed herein (including any accompanying claims, abstract, and drawings), and / or all steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The invention is not limited to the details of any of the foregoing embodiments. The invention extends to any novel or any novel combination of features disclosed herein (including any accompanying claims, abstract, and drawings), or any novel or any novel combination of steps of any method or process so disclosed.
[0023] The term "alkyl" refers to a monovalent or polyvalent, e.g., monovalent or divalent, straight-chain or branched, saturated hydrocarbon group of 1 to 6 carbon atoms, e.g., 1, 2, 3, 4, 5, or 6 carbon atoms ("C1-C6-alkyl"). In some embodiments, an alkyl group contains 1 to 3 carbon atoms, e.g., 1, 2, or 3 carbon atoms. Some non-limiting examples of alkyl include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, tert-butyl, and 2,2-dimethylpropyl. A particularly preferred, but non-limiting, example of alkyl is methyl.
[0024] The term "alkenyl" refers to a monovalent linear or branched hydrocarbon group of 2 to 6 carbon atoms having at least one double bond ("C2-C6-alkenyl"). In certain embodiments, an alkenyl has 2 to 4 carbon atoms having at least one double bond. Examples of alkenyl include ethenyl, propenyl, prop-2-enyl, isopropenyl, n-butenyl, and iso-butenyl. A particular alkenyl group is ethenyl.
[0025] The term "alkynyl" refers to a monovalent linear or branched hydrocarbon group of 2 to 6 carbon atoms having at least one triple bond ("C2-C6-alkynyl"). In certain embodiments, an alkynyl has 2 to 4 carbon atoms having at least one triple bond. Examples of alkynyl include ethynyl, propynyl, n-butynyl, or isobutynyl. A preferred alkenyl is propynyl.
[0026] The term "alkoxy" refers to an alkyl group, as defined above, attached to the parent molecular moiety through an oxygen atom. Unless otherwise specified, an alkoxy group contains 1 to 6 carbon atoms ("C1-C6-alkoxy"). In some preferred embodiments, an alkoxy group contains 1 to 4 carbon atoms. In still other embodiments, an 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 alkoxy is methoxy.
[0027] The term "halogen" or "halo" refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). Preferably, the term "halogen" or "halo" refers to fluoro (F), chloro (Cl), or bromo (Br). Particularly preferred, but non-limiting, examples of "halogen" or "halo" are fluoro (F) and chloro (Cl).
[0028] As used herein, the term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or bicyclic hydrocarbon group of 3 to 12 ring carbon atoms ("C3-C 12"-cycloalkyl" refers to a cycloalkyl moiety consisting of two saturated carbocyclic rings having two common carbon atoms, i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms, and a spirocyclic moiety, i.e., the two rings are joined through one common ring atom. Preferably, the cycloalkyl group is a saturated monocyclic hydrocarbon group of 3 to 6 ring carbon atoms, e.g., 3, 4, 5, or 6 carbon atoms. Some non-limiting examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.
[0029] The term "aminoalkoxy" refers to an alkoxy group in which at least one of the hydrogen atoms of the alkoxy group has been replaced with an amino group. Preferably, "aminoalkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkoxy group have been replaced with an amino group. A preferred, but non-limiting example of an aminoalkoxy is aminomethoxy.
[0030] The term "aminoalkyl" refers to an alkyl group in which at least one of the alkyl group's hydrogen atoms has been replaced with an amino group. Preferably, "aminoalkyl" refers to an alkyl group in which one, two, or three of the alkyl group's hydrogen atoms have been replaced with amino groups. A preferred, but non-limiting example of an aminoalkyl is aminomethyl.
[0031] The terms "heterocycloalkyl" and "heterocyclyl" are used interchangeably and refer to a saturated or partially unsaturated monocyclic or bicyclic, preferably monocyclic, ring system of 3 to 20 ring atoms, preferably 3 to 15 ring atoms, more preferably 3 to 10 ring atoms, and most preferably 3 to 6 ring atoms, in which 1, 2, or 3 of the ring atoms are heteroatoms selected from N, O, and S, and the remaining ring atoms are carbon ("C-C 19-heterocyclyl"). Preferably, 1 to 2 of the ring atoms are selected from N and O, and the remaining ring atoms are carbon. "Bicyclic heterocyclyl" refers to a heterocyclic moiety consisting of two rings having two ring atoms in common, i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms, and a spirocyclic moiety, i.e., the two rings are joined through one common ring atom. Some non-limiting examples of monocyclic heterocyclyl groups include azetidin-3-yl, azetidin-2-yl, oxetan-3-yl, oxetan-2-yl, 2-oxopyrrolidin-1-yl, 2-oxopyrrolidin-3-yl, 5-oxopyrrolidin-2-yl, 5-oxopyrrolidin-3-yl, 2-oxo-1-piperidyl, 2-oxo-3-piperidyl, 2-oxo-4-piperidyl, 6-oxo-2-piperidyl, 6-oxo-3-piperidyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, morpholino, morpholin-2-yl, and morpholin-3-yl.
[0032] The term "aryl" refers to a group having a total of 6 to 14 ring members ("C6-C 14 -aryl"), preferably a monocyclic, bicyclic, or tricyclic carbocyclic ring system having 6 to 12 ring members, more preferably 6 to 10 ring members, wherein at least one ring of the system is aromatic. Some non-limiting examples of aryl include phenyl and 9H-fluorenyl (e.g., 9H-fluoren-9-yl). A particularly preferred, but non-limiting example of aryl is phenyl.
[0033] 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, and more preferably 5 to 10 ring members, wherein at least one ring of the system is aromatic and at least one ring of 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 5 to 10-membered heteroaryl containing 1 to 2 heteroatoms independently selected from O and N. Some non-limiting examples of heteroaryl include 2-pyridyl, 3-pyridyl, 4-pyridyl, indol-1-yl, 1H-indol-2-yl, 1H-indol-3-yl, 1H-indol-4-yl, 1H-indol-5-yl, 1H-indol-6-yl, 1H-indol-7-yl, 1,2-benzoxazol-3-yl, 1,2-benzoxazol-4-yl, 1,2-benzoxazol-5-yl, 1,2-benzoxazol-6-yl, 1,2-benzoxazol-7-yl, 1H-indazol-3-yl, 1H-ind ...H-indazol-5-yl, 1H-indazol-6-yl, 1H-indazol-7-yl, 1H-indazol-3-yl, 1H-indazol-4-yl, 1H-indazol-5-yl, 1H-indazol-6-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol-7-yl, 1H-indazol- Indazol-4-yl, 1H-indazol-5-yl, 1H-indazol-6-yl, 1H-indazol-7-yl, pyrazol-1-yl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, imidazol-1-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, 1H-imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazolyl, pyrazolyl, pyridazinyl, pyrimidinyl, isoxazolyl and oxadiazolyl.
[0034] The term "hydroxy" refers to the group --OH.
[0035] The term "amino" refers to the group --NH.sub.2.
[0036] The term "cyano" refers to a -CN (nitrile) group.
[0037] The term "carboxy" refers to the group --COOH.
[0038] The term "guanidine" means [ka] Refers to the base.
[0039] The term "carbamoyl" refers to the group -C(O)NH2.
[0040] The term "carbonyl" refers to the group -C(O)-.
[0041] The term "alkoxycarbonyl" refers to a -C(O)-O-alkyl group (ie, an alkyl ester).
[0042] 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 fluoro. 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 fluoro. Particularly preferred, but non-limiting examples of haloalkyl are trifluoromethyl and trifluoroethyl.
[0043] The term "haloalkenyl" refers to an alkenyl group in which at least one of the hydrogen atoms of the alkenyl group has been replaced with a halogen atom, preferably fluoro. Preferably, "haloalkenyl" refers to an alkenyl group in which one, two, or three hydrogen atoms of the alkenyl group have been replaced with a halogen atom, most preferably fluoro. Particularly preferred, but non-limiting examples of haloalkenyl are 2-chloroallyl and 2-chloro-1-methyl-allyl.
[0044] 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 fluoro. 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. A particularly preferred, but non-limiting example of a haloalkoxy is trifluoromethoxy (-OCF).
[0045] The term "cyanoalkyl" refers to an alkyl group in which at least one of the alkyl group's hydrogen atoms has been replaced with a cyano group. Preferably, "cyanoalkyl" refers to an alkyl group in which one, two, or three of the alkyl group's hydrogen atoms have been replaced with a cyano group. A particularly preferred, but non-limiting, example of a cyanoalkyl is cyanomethyl.
[0046] The term "cycloalkylalkyl" refers to an alkyl group in which at least one of the alkyl group's hydrogen atoms is replaced by a cycloalkyl group. Preferably, "cycloalkylalkyl" refers to an alkyl group in which one, two, or three, most preferably one, hydrogen atom of the alkyl group is replaced by a cycloalkyl group. Particularly preferred, but non-limiting, examples of cycloalkylalkyl are cyclopropylmethyl and cyclobutylmethyl.
[0047] The term "alkyldiyl," as used herein, refers to a saturated, straight- or branched-chain divalent hydrocarbon radical of about 1 to 6 carbon atoms (C1 to C6). Examples of alkyldiyl groups include, but are not limited to, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), and the like. Alkyldiyl groups are sometimes referred to as "alkylene" groups.
[0048] The term "hydroxyalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by a hydroxy group. Preferably, "hydroxyalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms, most preferably one hydrogen atom, of the alkyl group is replaced by a hydroxy group. Preferred, but non-limiting, examples of hydroxyalkyl are hydroxymethyl and hydroxyethyl (e.g., 2-hydroxyethyl). A particularly preferred, but non-limiting, example of hydroxyalkyl is hydroxymethyl.
[0049] The term "hydroxyheterocyclyl" refers to a heterocyclyl group in which at least one of the hydrogen atoms of the heterocyclyl group has been replaced by a hydroxy group. Preferably, "hydroxyheterocyclyl" refers to a heterocyclyl group in which one, two, or three hydrogen atoms, most preferably one hydrogen atom, of the heterocyclyl group has been replaced by a hydroxy group. A particularly preferred, but non-limiting example of a hydroxyheterocyclyl is 4-hydroxypyrrolidin-2-yl.
[0050] The term "arylalkyl" refers to an alkyl group in which at least one of the alkyl group's hydrogen atoms has been replaced by an aryl group. Preferably, "arylalkyl" refers to an alkyl group in which one, two, or three, and most preferably one, hydrogen atom of the alkyl group has been replaced by an aryl group. Particularly preferred, but non-limiting, examples of arylalkyl are benzyl, phenylethyl (especially 2-phenylethyl), and phenylpropyl (especially 3-phenylpropyl).
[0051] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of the 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, phosphoric acid, especially hydrochloric acid, and organic acids such as acetic acid, 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, N-acetylcysteine, etc. In addition, these salts can be prepared by adding an inorganic or organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyimine resins, etc. Particular pharmaceutically acceptable salts of compounds of formula (I) are hydrochloride, fumarate, lactate (especially derived from L-(+)-lactic acid), tartrate (especially derived from L-(+)-tartaric acid), and trifluoroacetate.
[0052] The term "protecting group" (PG) refers to a group that selectively blocks a reactive site in a polyfunctional compound so that a chemical reaction, in the relevant conventional sense of synthetic chemistry, can be selectively carried out at an otherwise unprotected reactive site. The protecting group can be removed at an appropriate time. Exemplary protecting groups are amino-protecting groups, carboxy-protecting groups, or hydroxy-protecting groups. Particular protecting groups are tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc), and benzyl (Bn). Further particular protecting groups are tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). An even more particular protecting group is tert-butoxycarbonyl (Boc). Exemplary protecting groups and their use in organic synthesis are described, for example, in Protective Groups in Organic Chemistry, T.W. Greene and P.G.M. Hutts, 5th Edition, 2014, John Wiley & Sons, NY.
[0053] The compounds of formula (I) may contain several asymmetric centers and may exist as optically pure enantiomers, mixtures of enantiomers, e.g. racemates, optically pure diastereoisomers, mixtures of diastereoisomers, diastereomeric racemates or mixtures of diastereomeric racemates. According to the Cahn-Ingold-Prelog rules, the asymmetric carbon atom may be of the "R" or "S" configuration.
[0054] The term "treatment," as used herein, includes: (1) suppressing the symptom, disorder, or condition (e.g., in the case of maintenance treatment, arresting, reducing, or delaying the onset or recurrence of at least one clinical symptom or subclinical disease thereof); and / or (2) alleviating the condition (i.e., causing regression of the symptom, disorder, or condition, or at least one of its clinical symptoms or subclinical symptoms). The benefit to the patient to be treated is either statistically significant or at least discernible to the patient or physician. However, it will be understood that when a patient is administered a medication to treat a disease, the outcome may not necessarily be effective treatment.
[0055] The term "prophylaxis" as used herein includes preventing or delaying the appearance of clinical symptoms of a condition, disorder or condition that develops in a mammal, particularly in a human suffering from or susceptible to the condition, disorder or condition, but who has not yet experienced or exhibited clinical or asymptomatic symptoms of the condition, disorder or condition.
[0056] The term "mammal," as used herein, includes both humans and non-humans, including, but not limited to, humans, non-human primates, canines, felines, murines, bovines, equines, and porcines. In particularly preferred embodiments, the term "mammal" refers to humans.
[0057] The term "nosocomial infection" refers to a hospital-acquired infection (HAI), which is an infection acquired in a hospital or other health care facility. To emphasize both hospital and non-hospital settings, it is sometimes called a healthcare-associated infection (HAI or HCAI). Such infections may be acquired in hospitals, nursing homes, rehabilitation facilities, outpatient clinics, or other clinical settings. Compounds of the Invention
[0058] In a first aspect, the present invention provides a compound of formula (I): [ka] (I) (In the formula, (a) X is [ka] where: (i)R 1 and R 2 together with the N atom to which they are attached, form an optionally substituted C1-C 19 - forming a heterocyclic ring; or (ii)R 1 teeth, (i) Hydrogen; (ii) optionally substituted C1-C6-alkyl; (iii) optionally substituted C2-C6-alkenyl; (iv) optionally substituted C2-C6-alkynyl; (v) optionally substituted C1-C6-alkoxy; (vi) optionally substituted C1-C 19 -heterocyclyl; and (vii) optionally substituted C3-C 12 -cycloalkyl; R 2 is hydrogen or C1-C6 alkyl, or (b) X is [ka] where: R 1a teeth, (i) optionally substituted C1-C6-alkyl; (ii) optionally substituted C2-C6-alkenyl; (iii) optionally substituted C2-C6-alkynyl; (iv) optionally substituted C1-C 19 -heterocyclyl; and (v) optionally substituted C3-C 12 -cycloalkyl; R2a is C1-C6-alkyl; R 3 , R 4 , R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen, and C1-C6-alkyl; R 5 is halogen, cyano, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl, optionally substituted C1-C6-alkyl, C1-C6-alkyl-S- and groups [ka] selected from the group consisting of: R 6 and R 7 are independently hydrogen, halogen, cyano, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl, optionally substituted C1-C6-alkyl, C1-C6-alkyl-S- and groups [ka] selected from the group consisting of: L 1 is selected from the group consisting of carbonyl, a covalent bond, and C1-C6-alkyldiyl; A is an optionally substituted C3-C 12 -cycloalkyl, optionally substituted C1-C 19 -heterocyclyl, optionally substituted C6-C 14 -aryl, and optionally substituted C1-C 13 -heteroaryl), or a pharmaceutically acceptable salt thereof.
[0059] In one embodiment, the present invention provides a compound of formula (I) [ka] (I) (In the formula, (c) X is [ka] where: (iii)R 1 and R 2 together with the N atom to which they are attached, are optionally substituted C1-C 19 - forming a heterocyclic ring; or (iv)R 1 teeth, (viii) hydrogen; (ix) optionally substituted C1-C6-alkyl; (x) optionally substituted C2-C6-alkenyl; (xi) optionally substituted C2-C6-alkynyl; (xii) optionally substituted C1-C6-alkoxy; (xiii) optionally substituted C1-C 19 -heterocyclyl; and (xiv) optionally substituted C3-C 12 -cycloalkyl; R 2 is hydrogen or C1-C6 alkyl, or (d) X is [ka] where: R 1 teeth, (vi) optionally substituted C1-C6-alkyl; (vii) optionally substituted C2-C6-alkenyl; (viii) optionally substituted C2-C6-alkynyl; (ix) optionally substituted C1-C 19 -heterocyclyl; and (x) optionally substituted C3-C 12 -cycloalkyl; R 2 is C1-C6 alkyl; R 3 , R 4, R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 5 , R 6 and R 7 are independently hydrogen, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl, optionally substituted C1-C6-alkyl and groups [ka] independently selected from the group consisting of: L 1 is selected from the group consisting of carbonyl, a covalent bond, and C1-C6-alkyldiyl; A is an optionally substituted C3-C 12 -cycloalkyl, optionally substituted C1-C 19 -heterocyclyl, optionally substituted C6-C 14 -aryl, and optionally substituted C1-C 13 -heteroaryl), or a pharmaceutically acceptable salt thereof.
[0060] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: (a) X is [ka] where: (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, hydroxy and groups [ka] or (ii)R 1 but, (i) Hydrogen; (ii) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, halogen, cyano, hydroxy, and groups [ka] C1-C6-alkyl optionally substituted by one or more, preferably 1, 2, 3 or 4, substituents selected from the group consisting of: (iii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iv) C2-C6-alkynyl; (v) amino-C1-C6-alkoxy; and (vi) Group [ka] selected from the group consisting of: R 2 is hydrogen or C1-C6 alkyl, or (b) X is [ka] where: R 1a but, (i) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, halogen, cyano, hydroxy, and groups [ka] C1-C6-alkyl optionally substituted by one or more, preferably 1, 2, 3 or 4, substituents selected from the group consisting of: (ii)R10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iii) C2-C6-alkynyl; and (iv) group [ka] selected from the group consisting of: R 2a is C1-C6-alkyl; R 3 , R 4 , R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen, and C1-C6-alkyl; R 5 is halogen, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl, CF3, C1-C6-alkyl-S-, and groups [ka] wherein said C1-C6-alkyl is optionally substituted with one or more, preferably 1, 2, 3 or 4, substituents independently selected from the group consisting of C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkoxycarbonyl, hydroxy, halogen, (C1-C6-alkyl)2N-, C1-C6-alkyl-NH-, amino, carbamoyl, carboxy, cyano and CF3; R 6 and R 7 is hydrogen, halogen, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl, CF3, C1-C6-alkyl-S- and groups [ka] wherein said C-C-alkyl may be substituted with one or more, preferably 1, 2, 3 or 4, substituents independently selected from the group consisting of C-C-alkoxy, halo-C-C-alkoxy, C-C-alkoxycarbonyl, hydroxy, halogen, (C-C-alkyl)N-, C-C-alkyl-NH-, amino, carbamoyl, carboxy, cyano and CF3; R 10 are amino, C1-C6-alkyl-NH-, (C1-C6-alkyl)2N-, C2-C6-alkynyl, amino-C1-C6-alkyl-NH-, carbamoyl, guanidine, and C1-C 19 -heterocyclyl, wherein C-C 19 -heterocyclyl is optionally substituted by 1 or 2 substituents selected from hydroxy and cyano-C1-C6-alkyl; R 11 and R 12 Amino, hydroxy, hydroxy-C1-C 19 -heterocyclyl-C(O)- and hydroxy-C1-C 19 -heterocyclyl-C(O)-NH-; R 13 and R 14 are independently hydrogen, halogen, cyano, C1-C6-alkyl, amino, hydroxy, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, hydroxy-C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy, C6-C 14 -aryl-C1-C6-alkyl- and C3-C 12 -cycloalkyl-C1-C6-alkyl-; R 15 and R 16 is independently selected from the group consisting of hydrogen, amino, hydroxy, C1-C6-alkyl, and amino-C1-C6-alkyl; R 17is selected from the group consisting of hydrogen, halogen, amino, C1-C6-alkyl-NH- and (C1-C6-alkyl)2N-; R 18 and R 19 are independently selected from the group consisting of hydrogen, amino, hydroxy, and C1-C6-alkyl; L 1 is selected from the group consisting of carbonyl, a covalent bond and C1-C6-alkyldiyl; L 2 is selected from the group consisting of carbonyl, —C(O)—NH—, —NH—C(O)—, —NH—C(O)—NH—, —CH(NH)—C(O)—NH—, —NH—, and —O—; L 3 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—CH—; L 5 is selected from the group consisting of -CH2-C(O)-, -C(O)-CH2-, -CH2-NH-C(O)-, -NH-C(O)-CH2-, carbonyl, -NH-C(O)-, -C(O)-NH-, and -NH-C(O)-NH-; L 6 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; A, B, C and D are C3-C 12 -Cycloalkyl, C1-C 19 -heterocyclyl, C6-C 14 -aryl and C1-C 13 -heteroaryl; or a pharmaceutically acceptable salt thereof.
[0061] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: (a) X is [ka] where: (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, hydroxy and groups [ka] optionally substituted by one or more, preferably 1, 2, 3 or 4, substituents selected from the group consisting of: (ii)R 1 but, (i) Hydrogen; (ii) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, halogen, cyano, hydroxy and groups [ka] C1-C6-alkyl optionally substituted by one or more, preferably 1, 2, 3 or 4, substituents selected from the group consisting of: (iii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iv) C2-C6-alkynyl; (v) amino-C1-C6-alkoxy; and (vi) Group [ka] selected from the group consisting of: R 2 is hydrogen or C1-C6 alkyl, or (b) X is [ka] where: R1 but, (i) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, halogen, cyano, hydroxy and groups [ka] C1-C6-alkyl optionally substituted by one or more, preferably 1, 2, 3 or 4, substituents selected from the group consisting of: (ii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iii) C2-C6-alkynyl; and (iv) group [ka] selected from the group consisting of: R 2 is C1-C6 alkyl; R 3 , R 4 , R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen, and C1-C6-alkyl; R 5 , R 6 , and R 7 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl, CF3, and groups [ka] wherein said C-C-alkyl is optionally substituted with one or more, preferably one, two, three, or four, substituents independently selected from the group consisting of hydrogen, C-C-alkoxy, halo-C-C-alkoxy, C-C-alkoxycarbonyl, hydroxy, halogen, (C-C-alkyl)N—, C-C-alkyl-NH—, amino, carbamoyl, carboxy, cyano, and CF3; R 10 are amino, C1-C6-alkyl-NH-, (C1-C6-alkyl)2N-, C2-C6-alkynyl, amino-C1-C6-alkyl-NH-, carbamoyl, guanidine, and C1-C 19 -heterocyclyl, wherein C-C 19 -heterocyclyl is optionally substituted by 1 or 2 substituents selected from hydroxy and cyano-C1-C6-alkyl; R 11 and R 12 Amino, hydroxy, hydroxy-C1-C 19 -heterocyclyl-C(O)- and hydroxy-C1-C 19 -heterocyclyl-C(O)-NH-; R 13 and R 14 are independently hydrogen, halogen, cyano, C1-C6-alkyl, amino, hydroxy, amino-C1-C6-alkyl, cyano-C1-C6-alkyl, hydroxy-C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy, C6-C 14 -aryl-C1-C6-alkyl- and C3-C 12 -cycloalkyl-C1-C6-alkyl-; R 15 and R 16 is independently selected from the group consisting of hydrogen, amino, hydroxy and C1-C6-alkyl, and amino-C1-C6-alkyl; R 17 is selected from the group consisting of hydrogen, halogen, amino, C1-C6-alkyl-NH- and (C1-C6-alkyl)2N-; R 18 and R 19 are independently selected from the group consisting of hydrogen, amino, hydroxy, and C1-C6-alkyl; L 1 is selected from the group consisting of carbonyl, a covalent bond and C1-C6-alkyldiyl; L 2is selected from the group consisting of carbonyl, —C(O)—NH—, —NH—C(O)—, —NH—C(O)—NH—, —CH(NH)—C(O)—NH—, —NH—, and —O—; L 3 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—CH—; L 5 is selected from the group consisting of -CH2-C(O)-, -C(O)-CH2-, -CH2-NH-C(O)-, -NH-C(O)-CH2-, carbonyl, -NH-C(O)-, -C(O)-NH-, and -NH-C(O)-NH-; L 6 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; A, B, C and D are C3-C 12 -Cycloalkyl, C1-C 19 -heterocyclyl, C6-C 14 -aryl and C1-C 13 -heteroaryl; or a pharmaceutically acceptable salt thereof.
[0062] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) has the formula (II): [ka] (II) (In the formula, R 1 -R 9 is as defined herein) is a compound of
[0063] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) has the formula (III): [ka] (III) In the formula, R 1 -R 4 and R 6 -R 9 is as defined herein.
[0064] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) has the following formula (IV): [ka] (IV) (In the formula, R 1 -R 3 and R 6 is as defined herein) is a compound of
[0065] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, hydroxy and groups [ka] or (ii)R 1 but, (i) Hydrogen; (ii) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, cyano, hydroxy and groups [ka] C1-C6-alkyl optionally substituted by 1 to 2 substituents selected from the group consisting of: (iii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iv) C2-C6-alkynyl; (v) amino-C1-C6-alkoxy; and (vi) Group [ka] selected from the group consisting of: R 2 is hydrogen or C1-C6 alkyl, or a pharmaceutically acceptable salt thereof.
[0066] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, and groups [ka] or (ii)R 1 but, (i) Group [ka] C1-C6-alkyl substituted with one substituent selected from (ii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; R 2 is hydrogen, or a pharmaceutically acceptable salt thereof. In a particularly preferred embodiment, the present invention comprises: (i)R 1 and R 2 together with the N atom to which they are attached, form a C-C alkyl group selected from the group consisting of 1-piperidyl, 2,6-diazaspiro[3.3]heptan-2-yl, azetidin-1-yl, and piperazin-1-yl. 19 form a heterocyclic ring, wherein said C1-C 19 The heterocycle is R 17 -CH2-L 4 -, R 17 -CH(CH3)-L 4 -, R 17 -(CH2)3-L 4 -, amino, and groups [ka] or (ii)R 1 but, (i) Group [ka] ethyldiyl (-(CH2)2-) substituted with one substituent selected from: (ii)R 10 -(CH2)2-L 2 -(CH2)2-; (iii)R 10 -C(CH3)2-CH2-L 2 -(CH2)2-; (iv)R 10 -(CH2)2-L 2 -CH2-; and (v)R 10 -CH(CH3)-CH2-L 2 -(CH2)2-; R 2 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0067] In a preferred embodiment, the present invention provides R 3 is C1-C6-alkyl or halogen, or a pharmaceutically acceptable salt thereof.
[0068] In a particularly preferred embodiment, the present invention provides 3 is selected from the group consisting of methyl, ethyl, and chloro, or a pharmaceutically acceptable salt thereof.
[0069] In a preferred embodiment, the present invention provides R 4 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0070] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 5 is halogen, cyano, halo-C1-C6-alkyl, C1-C6-alkyl-S- or a group [ka] or a pharmaceutically acceptable salt thereof.
[0071] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 5 halo-C1-C6-alkyl or [ka] or a pharmaceutically acceptable salt thereof.
[0072] In a preferred embodiment, the present invention provides R 5 is halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.
[0073] In a particularly preferred embodiment, the present invention provides 5 is CF3 or CHF2, or a pharmaceutically acceptable salt thereof.
[0074] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 6 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl and groups [ka] wherein said C-C-alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C-C-alkoxy, halo-C-C-alkoxy, C-C-alkoxycarbonyl, hydroxy, halogen, (C-C-alkyl)N—, C-C-alkyl-NH—, amino, carbamoyl, carboxy, cyano and CF3, or a pharmaceutically acceptable salt thereof.
[0075] In a preferred embodiment, the present invention provides R 6 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl and groups [ka] wherein said C1-C6-alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C6-alkoxy, halogen, cyano and CF3, or a pharmaceutically acceptable salt thereof.
[0076] In a particularly preferred embodiment, the present invention provides 6 is hydrogen, methyl, ethyl, propyl, vinyl, prop-2-ynyl, halo-C2-C6-alkenyl and groups [ka] wherein said methyl, ethyl and propyl are optionally substituted with 1 to 2 substituents selected from the group consisting of methoxy, fluoro, cyano and CF3, or a pharmaceutically acceptable salt thereof.
[0077] In one embodiment, the present invention provides a compound comprising R 7 is hydrogen or C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.
[0078] In a preferred embodiment, the present invention provides R 7 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0079] In a preferred embodiment, the present invention provides R 8 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0080] In a preferred embodiment, the present invention provides R 9 is hydrogen or halogen, or a pharmaceutically acceptable salt thereof.
[0081] In a particularly preferred embodiment, the present invention provides 9 is hydrogen or fluoro; or a pharmaceutically acceptable salt thereof.
[0082] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 10is selected from the group consisting of amino, (C1-C6-alkyl)2N-, C2-C6-alkynyl, amino-C1-C6-alkyl-NH-, carbamoyl and guanidino, or a pharmaceutically acceptable salt thereof.
[0083] In a preferred embodiment, the present invention provides R 10 is amino, or a pharmaceutically acceptable salt thereof.
[0084] In a preferred embodiment, the present invention provides R 11 is hydroxy-C1-C 19 -heterocyclyl-C(O)- or a pharmaceutically acceptable salt thereof.
[0085] In a preferred embodiment, the present invention provides R 12 Amino and hydroxy-C1-C 19 -heterocyclyl-C(O)-NH- or a pharmaceutically acceptable salt thereof.
[0086] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 13 is hydrogen, halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, and C3-C 12 -cycloalkyl-C1-C6-alkyl- or a pharmaceutically acceptable salt thereof.
[0087] In a preferred embodiment, the present invention provides R 13 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0088] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 14is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.
[0089] In a preferred embodiment, the present invention provides R 14 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0090] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 15 is selected from the group consisting of hydrogen, amino and hydroxy, or a pharmaceutically acceptable salt thereof.
[0091] In a preferred embodiment, the present invention provides R 15 is hydrogen or amino, or a pharmaceutically acceptable salt thereof.
[0092] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 16 is hydrogen or C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.
[0093] In a preferred embodiment, the present invention provides R 16 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0094] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 17 is selected from the group consisting of hydrogen, amino and C1-C6-alkyl-NH-, or a pharmaceutically acceptable salt thereof.
[0095] In a preferred embodiment, the present invention provides R 17 is amino or C1-C6-alkyl-NH-, or a pharmaceutically acceptable salt thereof.
[0096] In a particularly preferred embodiment, the present invention provides 17 is amino or CH3NH-, or a pharmaceutically acceptable salt thereof.
[0097] In a preferred embodiment, the present invention provides R 18 is selected from the group consisting of hydrogen, amino and hydroxy, or a pharmaceutically acceptable salt thereof.
[0098] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 19 is hydrogen or C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.
[0099] In a preferred embodiment, the present invention provides R 19 is hydrogen, or a pharmaceutically acceptable salt thereof.
[0100] In a preferred embodiment, the present invention provides L 1 is selected from the group consisting of a covalent bond and C1-C6-alkyldiyl, or a pharmaceutically acceptable salt thereof.
[0101] In a particularly preferred embodiment, the present invention provides 1 is a covalent bond or —CH 2 —, or a pharmaceutically acceptable salt thereof.
[0102] In a preferred embodiment, the present invention provides L 2 is —NH—C(O)— or —O—, or a pharmaceutically acceptable salt thereof.
[0103] In a preferred embodiment, the present invention provides L 3is carbonyl or —C(O)—NH—, or a pharmaceutically acceptable salt thereof.
[0104] In a preferred embodiment, the present invention provides L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—, or a pharmaceutically acceptable salt thereof.
[0105] In a preferred embodiment, the present invention provides L 5 is carbonyl or -NH--C(O), or a pharmaceutically acceptable salt thereof.
[0106] In a preferred embodiment, the present invention provides L 6 is a covalent bond, or a pharmaceutically acceptable salt thereof.
[0107] In one embodiment, the present invention provides a method for treating a cancer comprising administering to a patient a cancer treatment ... 12 -Cycloalkyl, C1-C 19 -heterocyclyl and C1-C 13 -heteroaryl, or a pharmaceutically acceptable salt thereof.
[0108] In a preferred embodiment, the present invention provides a method for treating a cycloaliphatic disorder characterized in that A is C3-C 12 or a pharmaceutically acceptable salt thereof.
[0109] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is cyclopropyl or cyclobutyl.
[0110] In a preferred embodiment, the present invention provides a method for treating a cancer comprising administering to a patient a cancer treatment ... 19 -heterocyclyl or C3-C 12or a pharmaceutically acceptable salt thereof.
[0111] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, cyclopentyl, cyclobutyl, piperazin-1-yl, and 1-piperidyl.
[0112] In a preferred embodiment, the present invention provides a method for preparing a cycloaliphatic cyclohexyl group having a C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0113] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1-piperidyl, 3-piperidyl, cyclobutyl, and cyclopentyl.
[0114] In a preferred embodiment, the present invention provides a method for treating a cancer comprising administering to a patient a cancer-related disorder, in which D is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0115] In one embodiment, R 1a is amino-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.
[0116] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: (a) X is [ka] where: (i)R1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, hydroxy and groups [ka] or (ii)R 1 but, (i) Hydrogen; (ii) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, cyano, hydroxy and groups [ka] C1-C6-alkyl optionally substituted by 1 to 2 substituents selected from the group consisting of: (iii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iv) C2-C6-alkynyl; (v) amino-C1-C6-alkoxy; and (vi) Group [ka] selected from the group consisting of: R 2 is hydrogen or C1-C6 alkyl, or (b) X is [ka] where R 1a is amino-C1-C6-alkyl, and R 2a is C1-C6-alkyl; R 3is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 4 is hydrogen; R 5 is halogen, cyano, halo-C1-C6-alkyl, C1-C6-alkyl-S- or a group [ka] and; R 6 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl and groups [ka] wherein C-C-alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C-C-alkoxy, halo-C-C-alkoxy, C-C-alkoxycarbonyl, hydroxy, halogen, (C-C-alkyl)N—, C-C-alkyl-NH—, amino, carbamoyl, carboxy, cyano and CF3; R 7 is hydrogen or C1-C6 alkyl; R 8 is hydrogen; R 9 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 10 is selected from the group consisting of amino, (C1-C6-alkyl)2N-, C2-C6-alkynyl, amino-C1-C6-alkyl-NH-, carbamoyl, and guanidino; R 11 But hydroxy-C1-C 19 -heterocyclyl-C(O)-; R 12 but amino and hydroxy-C1-C 19 -heterocyclyl-C(O)-NH-; R 13is hydrogen, halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, and C3-C 12 -cycloalkyl-C1-C6-alkyl-; R 14 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 15 is selected from the group consisting of hydrogen, amino, and hydroxy; R 16 is hydrogen or C1-C6 alkyl; R 17 is selected from the group consisting of hydrogen, amino, and C1-C6-alkyl-NH-; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen or C1-C6 alkyl; L 1 is selected from the group consisting of carbonyl, a covalent bond, and C1-C6-alkyldiyl; L 2 is selected from the group consisting of -C(O)-NH-, -NH-C(O)-, -NH-C(O)-NH-, -CH(NH)-C(O)-NH-, -NH-, and -O-; L 3 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—CH—; L 5 is selected from the group consisting of -CH2-C(O)-, -C(O)-CH2-, -CH2-NH-C(O)-, -NH-C(O)-CH2-, carbonyl, -NH-C(O)-, -C(O)-NH-, and -NH-C(O)-NH-; L 6 is a covalent bond; A is C3-C 12 -Cycloalkyl, C1-C 19 -heterocyclyl, and C1-C13 - selected from the group consisting of heteroaryl; B is C1-C 19 -heterocyclyl or C3-C 12 -cycloalkyl; C is C1-C 19 -heterocyclyl or C3-C 12 -cycloalkyl; D is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0117] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, hydroxy and groups [ka] or (ii)R 1 but, (i) Hydrogen; (ii) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, cyano, hydroxy and groups [ka] C1-C6-alkyl optionally substituted by 1 to 2 substituents selected from the group consisting of: (iii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iv) C2-C6-alkynyl; (v) amino-C1-C6-alkoxy; and (vi) Group [ka] selected from the group consisting of: R 2 is hydrogen or C1-C6 alkyl; R 3 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 4 is hydrogen; R 5 halo-C1-C6-alkyl or [ka] and; R 6 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl and groups [ka] wherein C-C-alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C-C-alkoxy, halo-C-C-alkoxy, C-C-alkoxycarbonyl, hydroxy, halogen, (C-C-alkyl)N—, C-C-alkyl-NH—, amino, carbamoyl, carboxy, cyano and CF3; R 7 is hydrogen or C1-C6 alkyl; R 8 is hydrogen; R 9 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 10 is selected from the group consisting of amino, (C1-C6-alkyl)2N-, C2-C6-alkynyl, amino-C1-C6-alkyl-NH-, carbamoyl, and guanidino; R 11 But hydroxy-C1-C19 -heterocyclyl-C(O)-; R 12 but amino and hydroxy-C1-C 19 -heterocyclyl-C(O)-NH-; R 13 is hydrogen, halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, and C3-C 12 -cycloalkyl-C1-C6-alkyl-; R 14 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 15 is selected from the group consisting of hydrogen, amino, and hydroxy; R 16 is hydrogen or C1-C6 alkyl; R 17 is selected from the group consisting of hydrogen, amino, and C1-C6-alkyl-NH-; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen or C1-C6 alkyl; L 1 is selected from the group consisting of carbonyl, a covalent bond, and C1-C6-alkyldiyl; L 2 is selected from the group consisting of -C(O)-NH-, -NH-C(O)-, -NH-C(O)-NH-, -CH(NH)-C(O)-NH-, -NH-, and -O-; L 3 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—CH—; L 5is selected from the group consisting of -CH2-C(O)-, -C(O)-CH2-, -CH2-NH-C(O)-, -NH-C(O)-CH2-, carbonyl, -NH-C(O)-, -C(O)-NH-, and -NH-C(O)-NH-; L 6 is a covalent bond; A is C3-C 12 -Cycloalkyl, C1-C 19 -heterocyclyl, and C1-C 13 - selected from the group consisting of heteroaryl; B is C1-C 19 -heterocyclyl or C3-C 12 -cycloalkyl; C is C1-C 19 -heterocyclyl or C3-C 12 -cycloalkyl; D is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0118] In a preferred embodiment, the present invention provides (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, and groups [ka] or (ii)R 1 but, (i) Group [ka] C1-C6-alkyl substituted with one substituent selected from (ii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; R 2 is hydrogen; R 3 is C1-C6-alkyl or halogen; R 4 is hydrogen; R 5 is halo-C1-C6-alkyl; R 6 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl and groups [ka] wherein C1-C6-alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C6-alkoxy, halogen, cyano and CF3; R 7 is hydrogen; R 8 is hydrogen; R 9 is hydrogen or halogen; R 10 But in Amino: R 13 is hydrogen; R 14 is hydrogen; R 15 is hydrogen or amino; R 16 is hydrogen; R 17 is amino or C1-C6-alkyl-NH-; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 1is a covalent bond or -CH2-; L 2 is -NH-C(O)- or -O-; L 3 is carbonyl or -C(O)-NH-; L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—; L 5 is carbonyl or -NH-C(O)-; A is C3-C 12 -cycloalkyl; B is C1-C 19 -heterocyclyl or C3-C 12 -cycloalkyl; C is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0119] In a particularly preferred embodiment, the present invention comprises: (i)R 1 and R 2 together with the N atom to which they are attached, form a C-C alkyl group selected from the group consisting of 1-piperidyl, 2,6-diazaspiro[3.3]heptan-2-yl, azetidin-1-yl, and piperazin-1-yl. 19 form a heterocyclic ring, wherein said C1-C 19 The heterocycle is R 17 -CH2-L 4 -, R 17 -CH(CH3)-L 4 -, R 17 -(CH2)3-L 4 -, amino, and groups [ka] or (ii)R 1 but, (i) Group [ka] Ethyldiyl (-(CH2)2-) selected with one substituent selected from (ii)R 10 -(CH2)2-L 1 -(CH2)2-; (iii)R 10 -C(CH3)2-CH2-L 1 -(CH2)2-; (iv)R 10 -(CH2)2-L 1 -CH2-; and (v)R 10 -CH(CH3)-CH2-L 1 -(CH2)2-; and R 2 is hydrogen; R 3 is selected from the group consisting of methyl, ethyl, and chloro; R 4 is hydrogen; R 5 is CF3 or CHF2; R 6 is hydrogen, methyl, ethyl, propyl, vinyl, prop-2-ynyl, halo-C2-C6-alkenyl and groups [ka] wherein said methyl, ethyl and propyl are optionally substituted with 1 to 2 substituents selected from the group consisting of methoxy, fluoro, cyano and CF3; R 7 is hydrogen; R 8 is hydrogen; R 9 is hydrogen or fluoro; R 10 But in Amino: R 13 is hydrogen; R 14 is hydrogen; R 15 is hydrogen or amino; R 16 is hydrogen; R 17 is amino or CH3NH-; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 1 is a covalent bond or -CH2-; L 2 is -NH-C(O)- or -O-; L 3 is carbonyl or -C(O)-NH-; L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—; L 5 is carbonyl or -NH-C(O)-; A is cyclopropyl or cyclobutyl; B is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, cyclopentyl, cyclobutyl, piperazin-1-yl, and 1-piperidyl; and Provided herein is a compound of Formula (II), (III) or (IV) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1-piperidyl, 3-piperidyl, cyclobutyl and cyclopentyl.
[0120] In a particularly preferred embodiment, the group [ka] teeth, [ka] is selected from.
[0121] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is: N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (2S)-N-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide; [2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; 2-Amino-1-[4-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-(pyridin-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; [2-chloro-4-[difluoromethyl[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-3-[(3S)-pyrrolidin-3-yl]urea; 2-[4-[8-[4-[4-(3-aminocyclobutanecarbonyl)piperazine-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; N-[3-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-[4-[8-[3-chloro-4-[4-hydroxy-4-(methylaminomethyl)piperidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; 2-Ethyl-N-methyl-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(3-aminocyclobutanecarbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-(methoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl)-4-[[3-[1-(2,2-difluoroethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(methoxymethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-propyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-cyclopentyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide;hydrochloride N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-propan-2-yl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-methylbutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyclopropylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-ethyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1-(3,3,3-trifluoropropyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; (2S)-N-[2-[[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide; (2S)-N-[2-[[4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide; 4-[[3-[1-[[3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide; (2S)-N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]pyrrolidine-2-carboxamide; 2-Fluoro-6-methyl-N-prop-2-ynyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-Fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-prop-2-ynylbenzamide; 2-Fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methyl-N-prop-2-ynylbenzamide; 2-Fluoro-6-methyl-N-prop-2-ynyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-(3-aminopropyl)-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methylbenzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [4-(aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2S)-1-aminopropan-2-yl)-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [4-(aminomethyl)piperidin-1-yl]-[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylphenyl]methanone; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-6-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methylbenzamide; [4-(aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-Fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[3-(prop-2-ynylamino)propyl]benzamide; [2-fluoro-6-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]benzamide; [2-fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; [4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylphenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; [2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; 2-Fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methylphenyl]-piperazin-1-ylmethanone; 2-Fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methyl-N-[3-(prop-2-ynylamino)propyl]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methylbenzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]benzamide; 2-[4-[8-[3-fluoro-5-methyl-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-Amino-1-[4-[2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; [2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-(2,6-diazaspiro[3.3]heptan-2-yl)methanone; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(5-aminopentyl)-2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-[(2-methyl-1,3-thiazol-4-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride; N-[(2R)-1-aminopropan-2-yl]-2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-[(1-methylimidazol-2-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride; 2-Fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethylamino)-2-oxoethyl]-4-[[3-[1-but-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-chlorobenzamide formate; N-[(2R)-1-(4-aminopiperidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[(2R)-1-oxo-1-piperazin-1-ylpropan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[(2R)-1-[(3-aminocyclobutyl)amino]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[(2R)-1-oxo-1-[[(3R)-pyrrolidin-3-yl]amino]propan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[(2R)-1-[(3S)-3-aminopyrrolidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[(2R)-1-(2-aminoethylamino)-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[(2R)-1-oxo-1-[[(3S)-pyrrolidin-3-yl]amino]propan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[(2R)-1-[(3R)-3-aminopyrrolidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[(2R)-1-[2-(dimethylamino)ethylamino]-1-oxopropan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[(2R)-1-(3-aminoazetidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-[4-[8-[4-(3-aminoazetidine-1-carbonyl)-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; (3-aminoazetidin-1-yl)-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 2-[4-[8-[3-chloro-4-(2,6-diazaspiro[3.3]heptane-2-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; (4-aminopiperidin-1-yl)-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-aminopropan-2-yl)-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-aminopropan-2-yl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-(2,6-diazaspiro[3.3]heptan-2-yl)methanone; N,2-diethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N,2-diethylbenzamide; N,2-diethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; [2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; [2-chloro-4-[[3-[1-[(5-methyl-1H-pyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; [2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-prop-2-enylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-prop-2-ynylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; 2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 2-chloro-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2S)-1-(4-aminopiperidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[(2S)-1-oxo-1-[[(3S)-pyrrolidin-3-yl]amino]propan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; tert-Butyl N-[(2R)-2-[[2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]carbamate; tert-Butyl N-[(2R)-2-[[2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl]amino]propyl]carbamate; tert-Butyl N-[(2R)-2-[[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]propyl]carbamate; 2-Amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; 2-[4-[8-[4-[4-(2-aminoacetyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-(Azetidin-3-yl)-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; [2-chloro-4-[[3-[1-[(1-methylpyrazol-4-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; [2-chloro-4-[[3-[1-(pyridazin-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; N-[2-(4-aminopiperidin-1-yl]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(3-aminocyclobutyl)amino]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(2S)-1-oxo-1-piperazin-1-ylpropan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(3-aminoazetidin-1-yl]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]piperidine-4-carboxamide; (2S,4R)-N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-4-hydroxypyrrolidine-2-carboxamide; 1-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-3-[(3S)-pyrrolidin-3-yl]urea; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2,2,2-trifluoroacetic acid; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-[(2S)-2-aminopropoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; (2S,4R)-N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-4-hydroxypyrrolidine-2-carboxamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;2,2,2-trifluoroacetic acid; N-[2-[(2R)-2-aminopropoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]piperidine-4-carboxamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-[(6-methoxypyridazin-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; [2-chloro-4-[[3-[1-[(5-methylpyrimidin-2-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; [2-chloro-4-[[3-[1-[(4-methylpyrimidin-2-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; 2-chloro-N-(2-oxo-2-piperazin-1-ylethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-[(6-methylpyridazin-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[2-[2-(dimethylamino)ethylamino]-2-oxoethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (3-aminoazetidin-1-yl)-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 1-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-3-[(3R)-pyrrolidin-3-yl]urea; [2-chloro-4-[[3-[1-(pyrimidin-2-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]piperidine-4-carboxamide; 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-3-[(3R)-pyrrolidin-3-yl]urea; 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-3-[(3S)-pyrrolidin-3-yl]urea; (2S,4R)-N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-4-hydroxypyrrolidine-2-carboxamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (2S,4R)-N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-4-hydroxypyrrolidine-2-carboxamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride [2-chloro-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-[4-[8-[4-[4-(4-aminopiperidine-1-carbonyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; 2-[4-[8-[4-[4-[(3R)-3-aminopyrrolidine-1-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; 2-[4-[8-[4-[4-[(3S)-3-aminopyrrolidine-1-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; [2-chloro-4-[[3-[1-[(2-methylpyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; [2-chloro-4-[[3-[1-(pyrimidin-5-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; [2-chloro-4-[[3-[1-[(1-methylpyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; 2-Ethyl-N-[3-(prop-2-ynylamino)propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-[(1,5-dimethylpyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone formate; 2-[4-[8-[3-chloro-4-[4-[(2R)-pyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2S)-2-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2R)-2-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-(3-aminocyclobutanecarbonyl)piperazine-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; 2-[4-[8-[3-chloro-4-[4-[(3S)-pyrrolidine-3-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[3-chloro-4-[4-[(3R)-pyrrolidine-3-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(1S,3R)-3-aminocyclopentanecarbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; N-[3-(2-aminoethylcarbamoylamino)propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-[4-[8-[4-[4-[(1R,3S)-3-aminocyclopentanecarbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; N-[3-[[(2S)-2,6-diaminohexanoyl]amino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-Ethyl-N-[3-(prop-2-enylamino)propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2R)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; N-(4-aminocyclohexyl)-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; [4-[(2S,4R)-4-aminocypirrolidine-2-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; N-(2-aminoethoxy)-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-[4-[8-[4-(4-aminopiperidine-1-carbonyl)-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(3-ethoxypropyl)-2-ethylbenzamide; (2S)-2-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; (2R)-2-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; 2-[4-[8-[3-chloro-4-[4-[(2S)-pyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[3-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]propyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[3-(3-aminopropanoylamino)propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-(Azetidin-3-yl)-4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-[3-(4-aminobutanoylamino)propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(4-aminobutanoylamino)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethylcarbamoylamino)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-[4-[8-[3-ethyl-4-[4-hydroxy-4-(methylaminomethyl)piperidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; N-[2-(3-aminopropanoylamino)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-[[(2S)-2,6-diaminohexanoyl]amino]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethylcarbamoylamino)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-(3-ethoxypropyl)-2-ethyl-4-[[3-3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[2-[[(2S)-2,6-diaminohexanoyl]amino]ethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; [4-[(1R,2S)-2-aminocyclopropanecarbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; 2-[4-[8-[3-chloro-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(6-aminohexyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-(2-aminoethoxy)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-(2-aminoethyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-ethylbenzamide; 2-chloro-N-(cyanomethyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-but-3-yn-2-yl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[(1S,3R)-3-aminocyclopentyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(2-hydroxyethyl)benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-[(5-methyl-1,2-oxazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-[4-[8-[3-chloro-4-(3-hydroxyazetidine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(2R)-2-hydroxypropyl)benzamide; N-[(1R,3S)-3-aminocyclopentyl]-4-[2-chloro-4-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(2-methoxyethyl)benzamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(2S)-2-hydroxypropyl)benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(oxetan-3-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-[4-[8-[3-chloro-4-(3-hydroxy-3-methylazetidine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[3-chloro-4-[(3S)-3-hydroxypyrrolidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[3-chloro-4-[(3R)-3-hydroxypyrrolidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; [4-[(2R,4S)-4-aminocypirrolidine-2-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; N-(Azetidin-3-yl)-4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S)-3-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R)-3-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(cyanomethyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzamide; N-(4-aminocyclohexyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; 3-[4-[8-[4-[4-(3-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]propanenitrile formate; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; 2-[4-[8-[3-ethyl-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; 4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzamide; N-[2-(1-aminocyclopropyl)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-(3-aminocyclobutyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; [4-(3-aminoazetidine-1-carbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxy-2-methylpropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-hydroxybutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-pyrrolidin-1-ylethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-[2-(2-aminoethoxy)ethylcarbamoyl]-3-ethylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetic acid; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-cyclobutyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-chloroprop-2-enyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(3-chlorobut-3-en-2-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[(2,2-difluorocyclopropyl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(1-chloro-3-hydroxypropan-2-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[2-(chloromethyl)-3-hydroxy-2-methylpropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N,2-Diethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-methyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-Ethyl-N-methyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(2-aminoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; 2-chloro-N-methyl-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(4-aminopiperidine-1-carbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; 2-[4-[8-[4-[4-(3-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; N-(4-aminocyclohexyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; N-(3-aminocyclobutyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-(4-aminocyclohexyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-[(1S,3S)-3-Aminocyclopentyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; 3-amino-1-[4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; [4-[(2S,4S)-4-aminocypirrolidine-2-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; 4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; 4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; 2-Ethyl-N-methyl-4-[[3-[1-[2-(methylamino)ethyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(3-aminopropanoylamino)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(4-aminobutanoylamino)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyclobutylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[(3,3-difluorocyclobutyl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-hydroxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(oxolan-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[(3R)-1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[2-(dimethylamino)ethyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; Ethyl 2-[4-[8-[4-[2-(2-aminoethoxy)ethylcarbamoyl]-3-ethylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetate formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxy-3-methylbutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxypropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[(3S)-1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,3-dihydroxypropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,4-dihydroxybutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-morpholin-4-ylethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; (4-aminopiperidin-1-yl)-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-(5-aminopentyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; hydrochloride; [(3S)-3-aminopyrrolidin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[(3S)-3-methylpiperazin-1-yl]methanone; N-(2-aminoethyl)-2-chloro-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[(3R)-3-methylpiperazin-1-yl]methanone; [(3R)-3-aminopyrrolidin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[(2S)-2-methylpiperazin-1-yl]methanone; [4-[(3R)-3-aminopyrrolidine-1-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; [4-(3-aminocyclobutanecarbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; [4-[(3S)-3-aminopyrrolidine-1-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; N-(5-aminopentyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [4-(3-aminocyclobutanecarbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; (2S)-2-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; (2R)-2-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; 2-Ethyl-N-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(6-aminohexyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride; 4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; N-[3-(3-aminopropanoylamino)propyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride 4-[[3-[1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; [4-[(1R,3S)-3-aminocyclopentanecarbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; [4-[(1S,3R)-3-aminocyclopentanecarbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; 4-[[3-[1-(3-cyanopropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; N-[3-(4-aminobutanoylamino)propyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-chloro-N-[3-[[(2S)-2,6-diaminohexanoyl]amino]propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-propylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-methylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; 4-[[3-[1-(azetidin-3-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-chloro-N-methylbenzamide; hydrochloride; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-Ethyl-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(3-hydroxypiperidine-3-carbonyl)piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,5R)-5-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; [2-Ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone;hydrochloride; [2-Ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]methanone;hydrochloride; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 4-[[3-[1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-chloro-N-methylbenzamide; 2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 2-chloro-4-[[3-[1-(3-cyanopropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride N-(4-aminobutyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(2-aminoethyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide;hydrochloride; 2-[4-[8-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; (2S,4R)-N-[3-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]2-methylbenzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide formate; (2S,4R)-N-[3-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]cyclobutyl]-4-hydroxypyrrolidine-2-carboxamide; 2-chloro-N-[1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]azetidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(Aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone;hydrochloride; rac-(2R,4S)-N-[3-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]cyclopentyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4R)-N-[4-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]cyclohexyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4R)-N-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]2-methylbenzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide formate; 4-[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]-N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide formate; 2-chloro-N-[(3S)-pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(3R)-pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; Formic acid;2-[4-[8-[4-[4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-chloro-N-[1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperidin-4-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; Formic acid;2-[4-[8-[4-[4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(3-aminocyclobutyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(4-aminocyclohexyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[1-[rac-(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; N-(3-aminopropyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-(azetidin-3-ylmethyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-(azetidin-3-yl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 4-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]butan-1-one formate; 3-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone formate; 2-chloro-N,N-dimethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminocyclobutyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(4-aminocyclohexyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(azetidin-3-yl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[rac-(1R,3R)-3-aminocyclopentyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(azetidin-3-yl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; N-(azetidin-3-ylmethyl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 2-chloro-N-piperidin-4-yl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-piperidin-3-yl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; Formic acid;4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide; Formic acid;4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide; N-(3-aminopropyl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; 3-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one formate; 4-[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]-N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide formate; 4-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]butan-1-one; Formic acid;2-[4-[8-[4-[4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; Formic acid;2-[4-[8-[4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; Formic acid;2-[4-[8-[4-[4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; Formic acid;2-[4-[8-[4-[4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; Formic acid;2-[4-[8-[4-[4-(4-hydroxypiperidine-4-carbonyl)piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; Formic acid;2-[4-[8-[4-[4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(2-aminoethyl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide formate; (2S,4R)-N-[3-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; (2S,4R)-N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide formate; (2S,4R)-N-[2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide formate; (2S,4R)-N-[3-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide formate; (2S,4S)-4-Ethyl-N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide formate; [4-(3-Hydroxypiperidine-3-carbonyl)piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone;hydrochloride; (2S,4R)-N-[3-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide; [2-Methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,5R)-5-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone;hydrochloride; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide formate; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide formate; Formic acid;(2S,4R)-4-hydroxy-N-[3-[[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]pyrrolidine-2-carboxamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazin-1-yl]methanone formate; Formic acid;(2S,4R)-4-hydroxy-N-[2-[[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]pyrrolidine-2-carboxamide; (2S,4R)-N-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide formate; (2S,4S)-4-Ethyl-N-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide formate; (2S,4S)-N-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxy-4-methylpyrrolidine-2-carboxamide formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]methanone formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]methanone formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]methanone formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone formate; Formic acid;(2S,4R)-4-hydroxy-N-[3-[[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]pyrrolidine-2-carboxamide; Formic acid;(2S,4R)-4-hydroxy-N-[2-[[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]pyrrolidine-2-carboxamide; Formic acid;N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; Formic acid;N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; Formic acid;[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-Methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,4R)-4-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone;hydrochloride; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,4S)-4-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone;hydrochloride; Formic acid;N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; Formic acid;N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; Formic acid;[4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; Formic acid;[4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(2S,4R)-4-Hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone;hydrochloride; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-(4-(8-((4-(4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1R,3S)-3-(l2-Azanail)cyclopentane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)piperidine-4-carboxamide formate; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (S)-3-amino-N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)pyrrolidine-1-carboxamide formate; N-(2-((1R,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (S)-N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1R,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1R,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; cis-N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide formate; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide formate; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-(2,6-diazaspiro[3.3]heptan-2-yl)-2-oxo-ethyl]2-ethyl-benzamide formate; N-[2-(3-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-(3-methylpiperazin-1-yl)-2-oxo-ethyl]benzamide formate; N-[2-(6-amino-2-azaspiro[3.3]heptan-2-yl)-2-oxo-ethyl]4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-[3-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-[2-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-(3-Azaspiro[3.1.0]hexan-6-ylamino)-2-oxo-ethyl]4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-oxo-ethyl]2-ethyl-benzamide formate; N-(Azetidin-3-ylmethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; 2-Ethyl-N-(2-azaspiro[3.3]heptan-6-yl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(Azetidin-3-yl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone formate; (R)-3-amino-N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)pyrrolidine-1-carboxamide formate; ((3-aminopropyl)imino)(methyl)(2-methyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)-16-sulfanone; (4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone formate; (R)-3-amino-N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)pyrrolidine-1-carboxamide formate; N-[2-(Azetidin-3-ylmethylamino)-2-oxo-ethyl]4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-2-ylmethylamino)ethyl]benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-3-ylmethylamino)ethyl]benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(4-piperidylmethylamino)ethyl]benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-[(4-hydroxy-4-piperidyl)methylamino]-2-oxo-ethyl]benzamide formate; N-[2-(2,6-diazaspiro[3.3]heptan-2-yl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-[3-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-[2-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-(3-Azaspiro[3.1.0]hexan-6-ylamino)-2-oxo-ethyl]4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-(azetidin-2-ylmethylamino)-2-oxo-ethyl]4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(3-((1r,3r)-3-aminocyclobutane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(3-((1R,3S)-3-aminocyclopentane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(2-(3-aminopropanamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(4-aminobutanamido)ethyl]-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-[2-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-((1s,3s)-3-aminocyclobutyl)-4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(4-aminobutanamido)ethyl]-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1r,3r)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1R,3S)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-[2-(3-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-(3-methylpiperazin-1-yl)-2-oxo-ethyl]benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-[(3-hydroxyazetidin-3-yl)methylamino]-2-oxo-ethyl]benzamide formate; N-[2-(azetidin-3-ylmethylamino)-2-oxo-ethyl]4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-2-ylmethylamino)ethyl]benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-3-ylmethylamino)ethyl]benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(4-piperidylmethylamino)ethyl]benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-[(4-hydroxy-4-piperidyl)methylamino]-2-oxo-ethyl]benzamide formate; (2S,4R)—N-((1s,3R)-3-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)cyclobutyl)-4-hydroxypyrrolidine-2-carboxamide; N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)piperidine-4-carboxamide formate; N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)piperidine-4-carboxamide formate; (4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)(2,6-diazaspiro[3.4]octan-6-yl)methanone formate; (3-aminoazetidin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone formate; N-(Azetidin-3-ylmethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-amino-2-(chloromethyl)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)(1,6-diazaspiro[3.3]heptan-1-yl)methanone formate; (2-aminomethyl)-2-(chloromethyl)azetidin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone formate; (2,5-diazabicyclo[2.2.1]heptan-2-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone formate; N-(3-azabicyclo[3.1.0]hexan-6-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(piperidin-3-yl)benzamide formate; (4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)(1,6-diazaspiro[3.3]heptan-6-yl)methanone formate; N-(azetidin-3-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(3-aminopropanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; 4-amino-N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)piperidine-1-carboxamide formate; N-(2-(3-(3-aminopropyl)ureido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; 1-(4-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-2-(piperidin-4-yl)ethan-1-one formate; (4-(2-aminoethyl)piperazin-1-yl)(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone formate; 2-(4-(8-((3-chloro-4-(4-(2-(piperidin-4-yl)acetyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; 2-(4-(8-((4-(4-((1R,3R)-3-aminocyclopentane-1-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; (4-((1R,3R)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone formate; (4-((1S,3S)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone formate; (S)-3-amino-N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)pyrrolidine-1-carboxamide formate; (S)-3-amino-N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)pyrrolidine-1-carboxamide formate; 1-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-2-(piperidin-4-yl)ethan-1-one formate; 4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-N-((3-hydroxyazetidin-3-yl)methyl)piperazine-1-carboxamide formate; 4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-N-((3-hydroxyazetidin-3-yl)methyl)piperazine-1-carboxamide formate; N-(azetidin-3-yl)-4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carboxamide formate; 2-(4-(8-((4-(4-((1S,3S)-3-aminocyclopentane-1-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; (4-((1S,3S)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone formate; N-((1s,3s)-3-aminocyclobutyl)-4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carboxamide formate; N-((1s,3s)-3-aminocyclobutyl)-4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carboxamide formate; N-[2-[[(1R,3R)-3-aminocyclopentanecarbonyl]amino]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-(2-((1R,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; 4-((3-(1-((1-(cyanomethyl)-1H-pyrazol-3-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-methylbenzamide; 2-chloro-4-((3-(1-((1-(cyanomethyl)-1H-pyrazol-3-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-methylbenzamide; 2-chloro-4-((3-(1-(2-(dimethylamino)ethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-methylbenzamide formate; 4-((3-(1-(1-benzylpiperidin-4-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide formate; 4-((3-(1-((1-benzylpyrrolidin-3-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide formate; 4-((3-(1-(3-(4-(aminomethyl)phenyl)propyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide formate; 4-((3-(1-(3-(2-aminoethyl)benzyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide formate; N-[4-[N-(3-aminopropyl)-S-methyl-sulfonimidoyl]-3-methyl-phenyl]-3-[1-(cyclopropylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-amine formate; 2-[4-[8-[4-[N-(3-aminopropyl)-S-methyl-sulfonimidoyl]-3-methyl-anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(2-aminoethyl)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamidoformate; N-(azetidin-3-yl)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamidoformate; (S)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-N-(pyrrolidin-3-yl)acetamidoformate; (R)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-N-(pyrrolidin-3-yl)acetamidoformate; N-(2-aminoethyl)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamidoformate; N-(3-aminopropyl)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamidoformate; N-(azetidin-3-yl)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamidoformate; (S)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-N-(pyrrolidin-3-yl)acetamidoformate; N-(3-aminopropyl)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamidoformate; 2-(4-(8-((3-chloro-4-(4-(2-oxo-2-(piperazin-1-yl)ethyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; 2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-1-(piperazin-1-yl)ethan-1-one formate; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(3-aminopropoxy)ethyl)-2-ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(2-(2-aminoacetamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(3-aminopropoxy)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(2-(2-aminoethoxy)ethyl)-2-ethyl-4-((3-(1-(3-methylbut-2-en-1-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(6-aminohexyl]-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; (S)-N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 2-Ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)benzamide formate; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)benzamide formate; N-(2-(2-aminoacetamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)benzamide formate; N-(2-(2-aminoethoxy)ethyl)-2-ethyl-4-((3-(1-(2-trifluoromethoxy)ethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-((2-aminocyclopropyl)methyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; cis-N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (R)-N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (R)-N-(3-(2-aminopropanamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (S)—N-(3-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; (S)-N-(3-(2-aminopropanamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (4-(4-((3-(1-allyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)((2R,5S)-5-hydroxypyrrolidin-2-yl)methanone; N-(3-(3-aminopropanamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (R)-3-amino-N-(3-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)pyrrolidine-1-carboxamide; (R)-3-amino-N-(3-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-1-carboxamide formate; (R)-N-(3-(2-aminopropanamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (S)—N-(3-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)pyrrolidine-2-carboxamide; (S)-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(6-prolyl-2,6-diazaspiro[3.3]heptan-2-yl)methanone; (S)-2-(4-(8-((3-chloro-4-(6-prolyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (2S,4R)—N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)-4-hydroxypyrrolidine-2-carboxamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-((2-aminocyclopropyl)methyl)-2-ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-((2-aminocyclopropyl)methyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-[2-[(3-aminocyclobutyl)amino]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; (R)-N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(2-aminoethoxy)ethyl)-2-ethyl-4-((3-(1-(3,3,3-trifluoro-2-hydroxypropyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; 4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)benzamide formate; (4-(2-fluoro-6-methyl-4-((3-(1-(prop-2-yn-1-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)((2R,5S)-5-hydroxypyrrolidin-2-yl)methanone; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(1R)-1-methyl-2-oxo-2-piperazin-1-yl-ethyl]benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; (S)—N—((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; 2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)ethan-1-one; 2-amino-1-(6-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-2,6-diazaspiro[3.3]heptan-2-yl)ethan-1-one; (S)-N-[3-(2-aminopropanamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (1R,5S,6r)-N-((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-3-azabicyclo[3.1.0]hexane-6-carboxamide; (S)—N—((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(3-chloro-3-methylbutyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 2-amino-1-(6-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-2,6-diazaspiro[3.3]heptan-2-yl)ethan-1-one; 2-(4-(8-((3-chloro-4-(6-glycyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-[2-(3-aminocyclobutyl)amino-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)benzamide formate; (R)—N-(1-aminopropan-2-yl)-2-fluoro-6-methyl-4-((3-(1-(prop-2-yn-1-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; (S)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)propan-1-one; N-[(1R)-2-[(3S)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; (2S,4R)—N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)-4-hydroxypyrrolidine-2-carboxamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-[2-(dimethylamino)ethylamino]-2-oxo-ethyl]-2-ethyl-benzamide formate; N-((R)-1-((1s,3S)-3-aminocyclobutane-1-carboxamido)propan-2-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(3,3-difluorocyclobutyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-((2-aminocyclopropyl)methyl)-4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 2-ethyl-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)—N-(1-(2-aminoacetamido)propan-2-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; N-[(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-[(3-aminocyclobutyl)amino]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 2-(4-(8-((4-(4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazine-1-carbonyl)-3-fluoro-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; (R)-N-(3-(2-aminopropanamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[(1R)-1-methyl-2-oxo-2-piperazin-1-yl-ethyl]benzamide formate; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide formate; (R)-4-((3-(1-allyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(1-aminopropan-2-yl)-2-fluoro-6-methylbenzamide; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 2-(4-(8-((4-(4-(L-alanyl)piperazine-1-carbonyl)-3-fluoro-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; N-[(1R)-2-(3-aminocyclobutyl)amino-1-methyl-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; (2S,4R)—N—((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; (R)-3-amino-N-(3-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-1-carboxamide formate; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; (S)-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(6-propyl-2,6-diazaspiro[3.3]heptan-2-yl)methanone; (R)-N-(1-(2-aminoacetamido)propan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide formate; N-[(1R)-2-(4-amino-1-piperidyl)-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide formate; N-(2-(2-aminoacetamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylphenyl)methanone; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-[2-(dimethylamino)ethylamino]-2-oxo-ethyl]benzamide formate; (S)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; 2-(4-(8-((3-fluoro-4-(4-glycylpiperazine-1-carbonyl)-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; (R)-N-(2-(2-aminopropanamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-[(1R)-2-(4-amino-1-piperidyl)-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone; 2-(4-(8-((4-(4-((1s,3s)-3-aminocyclobutane-1-carbonyl)piperazine-1-carbonyl)-3-fluoro-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; N-((2-aminocyclopropyl)methyl)-4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (4-((1s,3s)-3-aminocyclobutane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylphenyl)methanone; N-(3-(3-aminopropanamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 2-(4-(8-((3-fluoro-5-methyl-4-(4-(piperidine-4-carbonyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; (R)—N-(1-aminopropan-2-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; (R)—N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)piperidine-4-carboxamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide formate; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone; 2-ethyl-N-(3-(2-(2,2,2-trifluoroacetamido)acetamido)propyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-((R)-1-((1s,3S)-3-aminocyclobutane-1-carboxamido)propan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide formate; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(1R)-1-methyl-2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (2S,4R)—N—((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; (4-(2-fluoro-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-6-methylbenzoyl)piperazin-1-yl)((2R,5S)-5-hydroxypyrrolidin-2-yl)methanone; 2-(4-(8-((3-fluoro-4-(4-((2R,5S)-5-hydroxypyrrolidine-2-carbonyl)piperazine-1-carbonyl)-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)benzamide formate; (S)-N-(2-(2-aminopropanamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (R)—N-(1-aminopropan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; (1R,5S,6r)-N-((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-3-azabicyclo[3.1.0]hexane-6-carboxamide formate; 2-(4-(8-((3-fluoro-4-(4-((2S,4R)-4-hydroxypyrrolidine-2-carbonyl)piperazine-1-carbonyl)-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; N-(R)-(1-((S)-2-aminopropanamido)propan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide formate; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[(1R)-2-(3-aminocyclobutyl)amino-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[(1R)-1-methyl-2-oxo-2-piperazin-1-yl-ethyl]benzamide formate; (2S,4R)—N-(3-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; N-[2-(2-aminoethylamino)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-[(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (4-((1r,3r)-3-aminocyclobutane-1-carbonyl)piperazin-1-yl)(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone; (R)—N-(1-aminopropan-2-yl)-2-fluoro-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-6-methylbenzamide; N-[(1R)-2-[(3S)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 2-Ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-(2-morpholinoethoxy)ethyl)benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[(1R)-1-methyl-2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide formate; N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)—N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)piperidine-4-carboxamide formate; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone; (4-((1r,3r)-3-aminocyclobutane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone; (2S,4R)—N—((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; 4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[(1R)-1-methyl-2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (R)-2-ethyl-N-(3-(2-(2,2,2-trifluoroacetamido)propanamido)propyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[2-[(3-aminocyclobutyl)amino]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-[2-(dimethylamino)ethylamino]-2-oxo-ethyl]-2-methylbenzamide formate; 2-Ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; (2S,4R)—N-(3-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; (4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypiperidin-4-yl)methanone; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; (S)-2-ethyl-N-(3-(2-(2,2,2-trifluoroacetamido)propanamido)propyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[2-(2-aminoethylamino)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide formate; N-[(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide formate; (S)—N-((R)-2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)pyrrolidine-2-carboxamide; (S)-(2-chloro-4-((3-(1-(difluoromethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(6-prolyl-2,6-diazaspiro[3.3]heptan-2-yl)methanone; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypiperidin-4-yl)methanone; N-[2-(2-aminoethylamino)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; (S)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (R)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)-3-methylbutan-1-one; (2S,4R)—N-((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide formate; (4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone formate; 2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; 2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)-3-methylbutan-1-one; (4-(4-((3-(1-allyl-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(2S,4R)-(4-hydroxypyrrolidin-2-yl)methanone; (S)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; N-((2-aminocyclopropyl)methyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (R)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (S)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-phenyl-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; (2S,4R)—N—((R)-2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; 2-Fluoro-6-methyl-N-[4-(prop-2-yn-1-ylamino)butyl]-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (2R)-2-amino-1-(4-(4-((3-(1-(but-3-yn-2-yl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one (mixture of epimers); (4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(2S,4R)-(4-hydroxypyrrolidin-2-yl)methanone; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(2S,4R)-(4-hydroxypyrrolidin-2-yl)methanone; (4-(4-((3-(1-(but-3-yn-2-yl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)((2R,4S)-4-hydroxypyrrolidin-2-yl)methanone (mixture of epimers); 2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; (S)—N-(3-(4-((3-(1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; N-[(1R)-2-(3-aminocyclobutyl)amino-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; (4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypiperidin-4-yl)methanone; 2-(3-(difluoromethyl)-4-(8-((3-ethyl-4-(4-(piperidine-4-carbonyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-1H-pyrazol-1-yl)acetonitrile; 2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; (S)-N-(3-(2-aminopropanamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(2S,4R)-(4-hydroxypyrrolidin-2-yl)methanone; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; 2-(4-(8-((4-(4-(D-valyl)piperazine-1-carbonyl)-3-ethylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(difluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypyrrolidin-2-yl)methanone; (2R)-2-amino-1-(4-(4-((3-(1-(but-3-yn-2-yl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)-3-methylbutan-1-one (mixture of epimers); 2-(4-(8-((4-(4-((1r,3r)-3-aminocyclobutane-1-carbonyl)piperazine-1-carbonyl)-3-ethylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(difluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)piperazin-1-yl)methanone; N-(3-(2-aminoacetamido)propyl]-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[(1R)-1-methyl-2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide formate; N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-[3-[(3-aminocyclobutanecarbonyl)amino]propyl]-4-[[3-[1-(3-aminocyclobutanecarbonyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (2-fluoro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(piperazin-1-yl)methanone trihydrochloride; (4-((1S,3R)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)2-fluorophenyl)methanone dihydrochloride; 2-(4-(8-((4-(4-((1S,3R)-3-aminocyclopentane-1-carbonyl)piperazine-1-carbonyl)-3-fluorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile dihydrochloride; (4-((1S,3R)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(cyclopropylmethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)2-fluorophenyl)methanone dihydrochloride; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzamide dihydrochloride; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzamide dihydrochloride; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(cyclopropylmethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzamide dihydrochloride; 2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzoyl)piperazin-1-yl)ethan-1-one dihydrochloride; 2-(4-(8-((3-fluoro-4-(4-glycylpiperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile dihydrochloride; 2-amino-1-(4-(4-((3-(1-(cyclopropylmethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzoyl)piperazin-1-yl)ethan-1-one dihydrochloride; N-(2-((2-((2-aminoethyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(2-((2-((azetidin-3-ylamino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (S)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)benzamide formate; (R)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)benzamide formate; N-(2-((2-((3-aminopropyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(2-((2-((2-aminoethyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; N-(2-((2-((azetidin-3-ylamino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (S)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)benzamide formate; (R)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)benzamide formate; N-(2-((2-((3-aminopropyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide formate; (1S,5R)-6-[[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]-1-methyl-imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]-N!-[(3R,4R)-4-hydroxypyrrolidin-3-yl]-3-azabicyclo[3.1.0]hexane-3-carboxamide; Formic acid N-(6-aminohexyl)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide hydrochloride; N-((1-(azetidin-3-ylmethyl)pyrrolidin-3-yl)methyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide bis(2,2,2-trifluoroacetate); N-((1-(azetidin-3-ylmethyl)piperidin-4-yl)methyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide 2,2,2-trifluoroacetate; 2-(Azetidin-3-ylmethyl-[5-[[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]pentyl]amino]acetic acid;Formic acid N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-cyano-1-(cyanomethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-cyano-1-(2,2-difluoroethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-methylsulfanyl-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; formic acid; and
[0122] N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-chloro-1-(cyanomethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is: N-[2-(2-aminoethoxy)ethyl]-2-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-(methoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methylbenzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-(2,6-diazaspiro[3.3]heptan-2-yl)methanone; 2-[4-[8-[3-chloro-4-(2,6-diazaspiro[3.3]heptane-2-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; [2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-[4-[(2S)-2-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2R)-2-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(1S,3R)-3-aminocyclopentanecarbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; 2-[4-[8-[3-chloro-4-[4-[(2S)-pyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-cyclobutyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide formate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; [4-[(3R)-3-aminopyrrolidine-1-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-propylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide formate; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]methanone formate; 2-(4-(8-((4-(4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate; N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1R,3S)-3-(l2-Azanail)cyclopentane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)piperidine-4-carboxamide formate; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (S)-3-amino-N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)pyrrolidine-1-carboxamide formate; N-(2-((1R,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; (S)-N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1R,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; N-(2-((1R,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; cis-N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide formate; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide formate; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate; and N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide formate.
[0123] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R13 is hydrogen, halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, and C3-C 12 -cycloalkyl-C1-C6-alkyl-; R 14 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; L 1 is selected from the group consisting of carbonyl, a covalent bond and C1-C6-alkyldiyl; A is C3-C 12 -Cycloalkyl, C1-C 19 -heterocyclyl, and C1-C 13 -heteroaryl, or a pharmaceutically acceptable salt thereof.
[0124] In a preferred embodiment, the present invention provides R 13 and R 14 are both hydrogen; L 1 is a covalent bond or -CH2-; and A is C3-C 12
[0013] Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R is -cycloalkyl. In a particularly preferred embodiment, the present invention comprises: R 13 and R 14 are both hydrogen; L 1 is a covalent bond or -CH2-; and Provided herein are compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein A is cyclopropyl or cyclobutyl.
[0125] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R 5 halo-C1-C6-alkyl or [ka] and; R 13 is hydrogen, halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, and C3-C 12 -cycloalkyl-C1-C6-alkyl-; R 14 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; L 1 is selected from the group consisting of carbonyl, a covalent bond and C1-C6-alkyldiyl; A is C3-C 12 -Cycloalkyl, C1-C 19 -heterocyclyl, and C1-C 13 -heteroaryl, or a pharmaceutically acceptable salt thereof.
[0126] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R 6 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl and groups [ka] wherein C-C-alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C-C-alkoxy, halo-C-C-alkoxy, C-C-alkoxycarbonyl, hydroxy, halogen, (C-C-alkyl)N—, C-C-alkyl-NH—, amino, carbamoyl, carboxy, cyano and CF3; R 13 is hydrogen, halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, and C3-C 12 -cycloalkyl-C1-C6-alkyl-; R 14 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; L 1is selected from the group consisting of carbonyl, a covalent bond, and C1-C6-alkyldiyl; A is C3-C 12 -Cycloalkyl, C1-C 19 -heterocyclyl, and C1-C 13 -heteroaryl, or a pharmaceutically acceptable salt thereof.
[0127] In a preferred embodiment, the present invention provides R 6 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkenyl and groups [ka] wherein C1-C6-alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C6-alkoxy, halogen, cyano and CF3; R 13 and R 14 are both hydrogen; L 1 is a covalent bond or -CH2-; and A is C3-C 12
[0013] Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R is -cycloalkyl.
[0128] In a particularly preferred embodiment, the present invention comprises: R 6 is hydrogen, methyl, ethyl, propyl, vinyl, prop-2-ynyl, halo-C2-C6-alkenyl and groups [ka] wherein said methyl, ethyl and propyl are optionally substituted with 1 to 2 substituents selected from the group consisting of methoxy, fluoro, cyano and CF3; R 13 and R 14are both hydrogen; L 1 is a covalent bond or -CH2-; and Provided herein are compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein A is cyclopropyl or cyclobutyl.
[0129] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R 15 is selected from the group consisting of hydrogen, amino, and hydroxy; R 16 is hydrogen or C1-C6 alkyl; L 3 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; B is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0130] In a preferred embodiment, the present invention provides R 15 is hydrogen or amino; R 16 is hydrogen; L 3 is carbonyl or —C(O)—NH—; and B is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof. In a particularly preferred embodiment, the present invention comprises: R 15 is hydrogen or amino; R 16 is hydrogen; L 3 is carbonyl or —C(O)—NH—; and Provided herein is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein B is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, cyclopentyl, cyclobutyl, piperazin-1-yl, and 1-piperidyl. In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen or C1-C6 alkyl; L 5 is selected from the group consisting of —CH—C(O)—, —C(O)—CH—, —CH—NH—C(O)—, —NH—C(O)—CH—, carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—NH—; and C is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0131] In a preferred embodiment, the present invention provides R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 5 is carbonyl or -NH-C(O)-, and C is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof. In a particularly preferred embodiment, the present invention comprises: R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 5 is carbonyl or -NH-C(O)-, and Provided herein is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein C is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1-piperidyl, 3-piperidyl, cyclobutyl, and cyclopentyl.
[0132] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R 11 But hydroxy-C1-C 19 -heterocyclyl-C(O)-; R 12 but amino and hydroxy-C1-C 19 -heterocyclyl-C(O)-NH-; L 6 is a covalent bond; D is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R 10 is selected from the group consisting of amino, (C1-C6-alkyl)2N-, C2-C6-alkynyl; amino-C1-C6-alkyl-NH-, carbamoyl, and guanidino; and L 2 is selected from the group consisting of —C(O)—NH—, —NH—C(O)—, —NH—C(O)—NH—, —CH(NH2)—C(O)—NH—, —NH—, and —O—, or a pharmaceutically acceptable salt thereof.
[0133] In a preferred embodiment, the present invention provides R 10 But in Amino: L 2 is —NH—C(O)— or —O—, or a pharmaceutically acceptable salt thereof.
[0134] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: R 17 is selected from the group consisting of hydrogen, amino, and C1-C6-alkyl-NH-; L 4 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—CH—, or a pharmaceutically acceptable salt thereof.
[0135] In a preferred embodiment, the present invention provides R 17 is amino or C1-C6-alkyl-NH-; and L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—, or a pharmaceutically acceptable salt thereof.
[0136] In a particularly preferred embodiment, the present invention comprises: R 17 is amino or CH3NH-; L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—, or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: (a) X is [ka] where: (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, hydroxy and groups [ka] or (ii)R 1 but, (i) Hydrogen; (ii) C2-C6-alkenyl-NH-, C1-C6-alkoxy, C1-C6-alkoxycarbonyl-NH-, C2-C6-alkynyl-NH-, amino, cyano, hydroxy and groups [ka] C1-C6-alkyl optionally substituted by 1 to 2 substituents selected from the group consisting of: (iii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; (iv) C2-C6-alkynyl; (v) amino-C1-C6-alkoxy; and (vi) Group [ka] selected from the group consisting of: R 2 is hydrogen or C1-C6 alkyl, or X is, [ka] where R 1a is amino-C1-C6-alkyl, and R 2a is C1-C6-alkyl; R 3 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R 4 is hydrogen; R 7 is hydrogen or C1-C6 alkyl; R 8 is hydrogen; R 9 is selected from the group consisting of hydrogen, halogen and C1-C6-alkyl; R10 is selected from the group consisting of amino, (C1-C6-alkyl)2N-, C2-C6-alkynyl, amino-C1-C6-alkyl-NH-, carbamoyl, and guanidino; R 11 But hydroxy-C1-C 19- heterocyclyl-C(O)-; R 12 but amino and hydroxy-C1-C 19 -heterocyclyl-C(O)-NH-; R 15 is selected from the group consisting of hydrogen, amino, and hydroxy; R 16 is hydrogen or C1-C6 alkyl; R 17 is selected from the group consisting of hydrogen, amino, and C1-C6-alkyl-NH-; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen or C1-C6 alkyl; L 2 is selected from the group consisting of -C(O)-NH-, -NH-C(O)-, -NH-C(O)-NH-, -CH(NH)-C(O)-NH-, -NH-, and -O-; L 3 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—CH—; L 5 is selected from the group consisting of -CH2-C(O)-, -C(O)-CH2-, -CH2-NH-C(O)-, -NH-C(O)-CH2-, carbonyl, -NH-C(O)-, -C(O)-NH-, and -NH-C(O)-NH-; L 6 is a covalent bond; B is C1-C 19 -heterocyclyl or C3-C12 -cycloalkyl; C is C1-C 19 -heterocyclyl or C3-C 12 -cycloalkyl; D is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof. In a preferred embodiment, the present invention provides (i)R 1 and R 2 together with the N atom to which they are attached, C1-C 19 - forms a heterocycle, where C1-C 19 -heterocycle is R 17 -C1-C6-Alkyl-L 4 -, amino, and groups [ka] or (ii)R 1 but, (i) Group [ka] C1-C6-alkyl substituted with one substituent selected from (ii)R 10 -C1-C6-Alkyl-L 2 -C1-C6-alkyl-; and R 2 is hydrogen; R 3 is C1-C6-alkyl or halogen; R 4 is hydrogen; R 7 is hydrogen; R 8 is hydrogen; R 9 is hydrogen or halogen; R10 But in Amino: R 15 is hydrogen or amino; R 16 is hydrogen; R 17 is amino or C1-C6-alkyl-NH-; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 2 is -NH-C(O)- or -O-; L 3 is carbonyl or -C(O)-NH-; L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—; L 5 is carbonyl or -NH-C(O)-; B is C1-C 19 -heterocyclyl or C3-C 12 -cycloalkyl; C is C1-C 19 -heterocyclyl or C3-C 12 or a pharmaceutically acceptable salt thereof.
[0137] In a particularly preferred embodiment, the present invention comprises: (i)R 1 and R 2 together with the N atom to which they are attached, form a C-C alkyl group selected from the group consisting of 1-piperidyl, 2,6-diazaspiro[3.3]heptan-2-yl, azetidin-1-yl, and piperazin-1-yl. 19 form a heterocyclic ring, wherein said C1-C 19 The heterocycle is R 17 -CH2-L 4 -, R 17 -CH(CH3)-L 4 -, R 17 -(CH2)3-L4 -, amino, and groups [ka] or (ii)R 1 but, (i) Group [ka] ethyldiyl (-(CH2)2-) substituted with one substituent selected from: (ii)R 10 -(CH2)2-L 1 -(CH2)2-; (iii)R 10 -C(CH3)2-CH2-L 1 -(CH2)2-; (iv)R 10 -(CH2)2-L 1 -CH2-; and (v)R 10 -CH(CH3)-CH2-L 1 -(CH2)2-; and R 2 is hydrogen; R 3 is selected from the group consisting of methyl, ethyl, and chloro; R 4 is hydrogen; R 7 is hydrogen; R 8 is hydrogen; R 9 is hydrogen or fluoro; R 10 But in Amino: R 15 is hydrogen or amino; R 16 is hydrogen; R 17 is amino or CH3NH-; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 2 is -NH-C(O)- or -O-; L 3 is carbonyl or -C(O)-NH-; L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—; L 5 is carbonyl or -NH-C(O)-; B is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, cyclopentyl, cyclobutyl, piperazin-1-yl, and 1-piperidyl; and Provided herein is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein C is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1-piperidyl, 3-piperidyl, cyclobutyl, and cyclopentyl.
[0138] In one embodiment, the present invention provides a pharmaceutically acceptable salt of a compound of formula (I) described herein, particularly a pharmaceutically acceptable salt selected from hydrochloride, fumarate, lactate (particularly derived from L-(+)-lactic acid), tartrate (particularly derived from L-(+)-tartaric acid), and trifluoroacetate. In a further particular embodiment, the present invention provides a compound of formula (I) described herein (i.e., as the "free base" or "free acid," respectively).
[0139] In some embodiments, compounds of formula (I) are isotopically labeled by replacing one or more atoms therein with atoms having a different atomic mass or mass number. Such isotopically labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of the present disclosure. Exemplary isotopes that can be incorporated into compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, e.g., 2 H, 3 H, 11C. 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 Certain isotopically labeled compounds of formula (I), for example, those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotope tritium, i.e., 3 H and carbon-14, i.e., 14 C are particularly useful for this purpose given their ease of incorporation and ready means of detection. For example, compounds of formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99% of a given isotope.
[0140] Heavier isotopes, such as deuterium, i.e. 2 Substitutions such as H may result in greater metabolic stability and may confer certain therapeutic advantages, for example, by increasing in vivo half-life or requiring lower dosages.
[0141] 11 C. 18 F, 15 O and 13 Substitution with positron emitting isotopes, such as N, can be useful in positron emission tomography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art, or by processes analogous to those described in the Examples set forth below, substituting appropriate isotopically labeled reagents for previously employed non-isotopically labeled reagents. Manufacturing Process
[0142] The preparation of the compounds of Formula I of the present invention can be carried out 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 carry out the reactions and purification of the resulting products are known to those skilled in the art. The substituents and indices used in the following method descriptions have the meanings previously indicated 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. Suitable reaction conditions for the individual reaction steps are known to those skilled in the art. For literature-described reaction conditions affecting the reactions described, see, for example, Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock, John Wiley & Sons, New York, NY, 1999. The present inventors have found it convenient to carry out the reactions in the presence or absence of a solvent. There are no particular limitations on the nature of the solvent used, provided it does not adversely affect the reaction or the reagents involved and is capable of dissolving the reagents to at least some extent. The reactions described can occur over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reactions described at temperatures ranging from -78°C to reflux. The time required for the reaction can also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents. However, a period of 0.5 hours to several days will usually be sufficient to obtain the intermediates and compounds described. The reaction sequence is not limited to that shown in the schemes, but the order of the reaction steps can be freely changed depending on the starting materials and their respective reactivities. The starting materials are commercially available or can be prepared by methods similar to those shown below, methods described in the references or examples cited herein, or methods known in the art. Scheme 1: [ka]
[0143] a) 8-Chloro-3-iodoimidazo[1,2-a]pyrazine II is commercially available and can be conveniently reacted with aniline derivative III under acidic or basic conditions in a suitable solvent in the presence or absence of a transition metal catalyst (depending on the nature and therefore reactivity of the selected aniline derivative III), depending on the reagent selected to access imidazo-pyrazine derivative IV. When R=alkyl, the ester functionality can be cleaved under appropriate acidic or basic conditions to access acid derivative III.
[0144] b) Acid or ester derivatives III can be conveniently reacted with amines V (primary, secondary, or further protected bisamines) in the presence of a coupling reagent (such as HATU, TBTU), in the presence of a solvent (such as DMF, dioxane, and THF), and in the presence of a base (such as DIPEA and triethylamine) to access imidazopyridazines VI. These compounds can be intermediates utilized in subsequent Suzuki reactions, but if amine VI is a selected, further protected bisamine, the protecting group can be cleaved under appropriate conditions and the free amine functionality further derivatized to form an amide or urea.
[0145] c) Imidazopyrazine VI can be conveniently subjected to a transition metal catalyzed Suzuki reaction with boronic acids or esters VII (typical metal source: Pd, etc.) in solvents such as dioxane, DMF, and THF in the presence of bases such as NEt, DIPEA, and carbonates to give imidazopyrazine derivatives I. These can be final compounds, but further transformations at the pyrazole ring system or at the amide moiety provide access to the final imidazopyrazine derivatives I.
[0146] d) 8-Chloro-3-iodoimidazo[1,2-a]pyrazine I is commercially available and can be conveniently subjected to transition metal catalyzed Suzuki reaction with boronic acids or esters VII (typical metal source: Pd, etc.) in solvents such as dioxane, DMF, and THF in the presence of bases such as NEt, DIPEA, and carbonates to give imidazopyrazine derivatives VIII.
[0147] e) The imidazopyrazine derivative VIII can be conveniently reacted with the aniline derivative III under acidic or basic conditions in a suitable solvent in the presence or absence of a transition metal catalyst (depending on the nature and therefore the reactivity of the selected aniline derivative III), depending on the reagent selected to access the imidazopyrazine derivative IV. When R=alkyl, the ester functionality can be cleaved under appropriate acidic or basic conditions to access the acid derivative IX.
[0148] f) The acid or ester derivatives IX can be conveniently reacted with amines V (primary, secondary, or further protected bisamines) in the presence of a coupling reagent (such as HATU, TBTU), in the presence of a solvent (such as DMF, dioxane, and THF), and in the presence of a base (such as DIPEA and triethylamine) to access the imidazopyridazines I. These may be the final compounds, but further transformations at the pyrazole ring system allow access to the final imidazopyrazine derivatives I. Alternatively, if the amine VI is a selected, further protected bisamine, the protecting group can be cleaved under appropriate conditions, and the free amine functionality can be further derivatized to form an amide or urea as the final imidazopyrazine derivatives I.
[0149] The following substructure [ka] Compounds having the formula: can be synthesized as shown in Scheme 2: [ka]
[0150] a) Intermediates of type VIII can be reacted with intermediates of type Xa as described in Scheme 1, condition a. These can then be followed by other potentially necessary steps as described in Scheme 1, such as deprotection. In this context, R 6 In the case of =H, an appropriate protecting group for this position may be used. When starting from VIIIa, a transition metal catalyzed reaction is preferred for the first step.
[0151] b) Intermediates of type VIII can be converted to intermediates of type VIIIa by heating with aqueous ammonia in a suitable solvent in a sealed apparatus.
[0152] Intermediates Xa and Xb can be synthesized as shown in Scheme 3: [ka]
[0153] a) 4-Fluoronitrobenzene can be reacted with the corresponding sulfide or sulfide salt in a suitable solvent, usually at elevated temperature.
[0154] b) The resulting thioether can then be converted to the corresponding sulfoximine by reaction with ammonium carbamate and iodobenzene diacetate in a suitable solvent, usually at or slightly below room temperature.
[0155] c) The resulting sulfoximine can then be alkylated using the corresponding alkyl halide in the presence of a suitable base in a suitable solvent, usually at elevated temperature.
[0156] d) The nitro group still present can be reduced to the corresponding aniline in a number of ways. One possibility is reaction with sodium borohydride in the presence of nickel(II) chloride in a suitable solvent.
[0157] In one aspect, the present invention provides a process for preparing a compound of formula (I) described herein, comprising: (i) Carboxylic acid IXa [wherein R 3 -R 7 is as defined herein] [ka] (IXa), Amine V [wherein R 1 and R 2 is as defined herein] [ka] (V) and reacting in the presence of a coupling reagent (such as HATU, TBTU, etc.) and a base (such as DIPEA, NEt3, etc.) to form a compound of formula (I) as described above; or (ii) Compound VIa [wherein R 1 ~R 4 , R 8 and R 9 is as defined herein and Z is halogen or triflate. [ka] (VIa), Compound VIIa [wherein, R 5 ~R 7 is as defined herein, and Y is a boronic acid or boronic ester. [ka] reacting with VIIa, reacting in a solvent (e.g., dioxane, DMF, THF, etc.) in the presence of a transition metal catalyst (e.g., PdCl(dppf)-CHCl adduct, Pd(PPh) and a base (e.g., NEt, DIPEA, carbonate, KPO, NaOtBu, etc.) to form a compound of formula (I).
[0158] In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, when prepared according to the methods disclosed herein.
[0159] Uses of the Compounds of the Invention As shown in the experimental section, the compounds of formula (I) and their pharmaceutically acceptable salts possess valuable pharmacological properties for the treatment or prevention of infections and resultant diseases caused by pathogens, particularly bacteria, more particularly Acinetobacter species, and most particularly Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections.
[0160] The compounds of formula (I) and their pharmaceutically acceptable salts exhibit activity as antibiotics, particularly as antibiotics against Acinetobacter species, more particularly as antibiotics against Acinetobacter baumannii, and most particularly as pathogen-specific antibiotics against Acinetobacter baumannii.
[0161] The compounds of formula (I) and their pharmaceutically acceptable salts can be used as antibiotics, i.e., as suitable antibacterial pharmaceutical ingredients in the treatment and prevention of bacterial infections, in particular bacterial infections caused by Acinetobacter species, more particularly bacterial infections caused by Acinetobacter baumannii.
[0162] The compounds of the present invention can be used, alone or in combination with other drugs, for the treatment or prevention of infections and resultant diseases caused by pathogens, particularly bacteria, more particularly Acinetobacter species, most particularly Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections and wound infections.
[0163] In one aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.
[0164] In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use as an antibiotic.
[0165] In a further aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of hospital-acquired infections and resulting diseases.
[0166] In certain embodiments, the nosocomial infection and resulting disease is selected from bacteremia, pneumonia, meningitis, urinary tract infections and wound infections, or a combination thereof.
[0167] In a further aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of infections and resulting diseases caused by Gram-negative bacteria.
[0168] In certain embodiments, said infections and resulting diseases caused by Gram-negative bacteria are selected from bacteremia, pneumonia, meningitis, urinary tract infections and wound infections, or combinations thereof.
[0169] In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species or Escherichia coli, or combinations thereof.
[0170] In a further aspect, the present invention provides a method 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, or combinations thereof, comprising administering to a mammal a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.
[0171] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, as an antibiotic.
[0172] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli, or combinations thereof.
[0173] In a further aspect, the present invention provides the use of a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament useful for the treatment or prevention of infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli, or a combination thereof.
[0174] 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, or a combination thereof, is selected from bacteremia, pneumonia, meningitis, urinary tract infections, and wound infections, or a combination thereof.
[0175] In a further aspect, the present invention provides a pharmaceutically acceptable salt thereof as defined above for use in the treatment or prevention of infections and resulting diseases caused by pathogens, in particular bacteria, more particularly Acinetobacter species, most particularly Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections and wound infections.
[0176] In a further aspect, the present invention provides a method for the treatment or prevention of infections and resulting diseases, particularly bacteremia, pneumonia, meningitis, urinary tract infections and wound infections caused by pathogens, particularly bacteria, more particularly Acinetobacter species, most particularly Acinetobacter baumannii, which method comprises administering to a mammal a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof.
[0177] In a further aspect, the present invention provides the use of a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of infections and resulting diseases caused by pathogens, in particular bacteria, more particularly Acinetobacter species, most particularly Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections and wound infections.
[0178] In a further aspect, the present invention provides the use of a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of infections and resulting diseases caused by pathogens, particularly bacteria, more particularly Acinetobacter species, most particularly Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections and wound infections. Such a medicament comprises a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof.
[0179] Pharmaceutical Compositions and Administration In one aspect, 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 834-837.
[0180] In a further aspect, 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, in particular bacteria, more particularly Acinetobacter species, most particularly Acinetobacter baumannii, in particular bacteremia, pneumonia, meningitis, urinary tract infections and wound infections.
[0181] The compounds of formula (I) and their pharmaceutically acceptable salts can be used as medicines (e.g., in the form of pharmaceutical preparations). Pharmaceutical preparations can be administered to the body orally (e.g., in the form of tablets, coated tablets, sugar-coated tablets, hard and soft gelatin capsules, liquids, emulsions, or suspensions), nasally (e.g., in the form of nasal sprays), or rectally (e.g., in the form of suppositories). However, administration can also be carried out parenterally, for example, intramuscularly or intravenously (e.g., in the form of injections or infusions).
[0182] The compound of formula (I) and its pharmaceutically acceptable salts can be processed with pharmaceutically inert inorganic or organic additives for the preparation of tablets, coated tablets, dragees, and hard gelatin capsules. Lactose, corn starch or its derivatives, talc, stearic acid or its salts, etc. can be used as such additives for tablets, dragees, and hard gelatin capsules.
[0183] Suitable excipients for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semisolid substances, and liquid polyols.
[0184] Suitable additives for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar, glucose etc.
[0185] Suitable excipients for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils and the like.
[0186] Suitable excipients for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols etc.
[0187] In addition, pharmaceutical preparations may contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavoring agents, salts for varying osmotic pressure, buffers, masking agents, or antioxidants, and may also contain other therapeutically valuable substances.
[0188] The dosage can vary widely and will of course be adapted to the individual requirements of each particular case.Generally, for oral administration, a daily dosage of about 0.1 mg to 20 mg / kg body weight, preferably about 0.5 mg to 4 mg / kg body weight (for example, about 300 mg / person) will be appropriate, preferably divided into 1 to 3 individual dosages, for example, of the same amount.However, it is clear that the upper limit given herein can be exceeded in indicated cases.
[0189] Co-administration of Compounds of Formula (I) with Other Drugs The compound of Formula (I) or its salt, or the compounds disclosed herein or their pharmaceutically acceptable salts, can be used alone or in combination with other drugs for treatment. For example, the second drug in a combined pharmaceutical formulation or administration regimen may have complementary activity to the compound of Formula (I) so that they do not adversely affect each other. The compounds may be administered together in a single pharmaceutical composition or separately. In one embodiment, the compound or its pharmaceutically acceptable salt can be co-administered with an antibiotic, particularly 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, or a combination thereof.
[0190] The term "co-administering" refers to simultaneous administration or any manner of separate, consecutive administration of the compound of formula (I) or its salt, or the compound disclosed herein or its pharmaceutically acceptable salt, and one or more additional active pharmaceutical ingredients, including antibiotic preparations.If administration is not simultaneous, the compounds are administered close to each other in time.In addition, it is not important whether the compounds are administered in the same dosage form, for example, one compound may be administered intravenously and another compound may be administered orally.
[0191] Typically, drugs with antibacterial activity may be co-administered. Specific examples of such drugs are carbapenems (meropenem), fluoroquinolones (ciprofloxacin), aminoglycosides (amikacin), tetracyclines (tigecycline), colistin, sulbactam, sulbactam plus durrobactam, cefiderocol (fetroja), macrocyclic peptides, and macrolides (erythromycin), as exemplified, for example, in WO2017072062, WO2019185572, and WO2019206853.
[0192] In one aspect, the present invention provides a pharmaceutical composition described herein further comprising an additional therapeutic agent.
[0193] In one aspect, the present invention provides a pharmaceutical combination comprising a compound of Formula (I) described herein and an additional therapeutic agent.
[0194] In one embodiment, the additional therapeutic agent is an antibiotic agent.
[0195] In one embodiment, the additional therapeutic agent is an antibiotic agent useful for the treatment or prevention of infection and resulting disease caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, or Escherichia coli, or a combination thereof.
[0196] In one embodiment, the additional therapeutic agent is an antibiotic agent selected from a carbapenem (meropenem), a fluoroquinolone (ciprofloxacin), an aminoglycoside (amikacin), a tetracycline (tigecycline), colistin, sulbactam, sulbactam plus durrobactam, cefiderocol (fetroja), a macrocyclic peptide, and a macrolide (erythromycin), as exemplified in WO2017072062, WO2019185572, and WO2019206853. [Example]
[0197] The present invention will be more fully understood by reference to the following examples, which should not, however, be construed as limiting the scope of the claims to the examples.
[0198] Where preparations are obtained as mixtures of enantiomers, the pure enantiomers can be separated by the methods described herein or by methods known to those skilled in the art, such as chiral chromatography (e.g., chiral SFC) or crystallization.
[0199] Unless otherwise stated, all reactions and intermediates were prepared under an argon atmosphere.
[0200] Example 1 N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide [ka]
[0201] Step 1: Methyl 2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoate
[0202] A mixture of 8-chloro-3-iodoimidazo[1,2-a]pyrazine (18 g, 64.4 mmol) and methyl 4-amino-2-ethylbenzoate (13.3 g, 74.1 mmol) in acetonitrile (140 mL) and acetic acid (14.7 g, 14 mL) was heated to 85 °C. After cooling to room temperature, the precipitate was filtered off, washed with acetonitrile / methanol 1:1, and dried to give the title compound as off-white crystals (28.6 g, 62.4 mmol, 97%). MS (m / e): 423.1 (M+H).
[0203] Step 2: 2-Ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]hydrochloride
[0204] Methyl 2-ethyl-4-((3-iodoimidazo[1,2-a]pyrazin-8-yl)amino)benzoate (1.48 g, 3.23 mmol) and LiOH . A mixture of HO (677 mg, 16.1 mmol) in THF (30 mL), water (15 mL), and MeOH (15 mL) was heated to 60 °C and stirred overnight. The reaction mixture was concentrated in vacuo and poured into 30 mL of 1 M HCl. The precipitate was filtered through sintered glass, washed with water, and dried under high vacuum for 2 h to give the title compound as a white solid (1.421 g, 3.2 mmol, 99%). MS (m / e): 409.1 (M+H).
[0205] Step 3: tert-Butyl N-[2-[2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]ethoxy]ethyl]carbamate
[0206] A mixture of 2-ethyl-4-((3-iodoimidazo[1,2-a]pyrazin-8-yl)amino)benzoic acid hydrochloride (1.421 g, 3.2 mmol), TBTU (1.22 g, 3.68 mmol), tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (816 mg, 3.99 mmol), and triethylamine (1.62 g, 2.23 mL, 16 mmol) in DMF (20 mL) was stirred at room temperature overnight. The reaction mixture was poured into 150 mL of water and extracted with ethyl acetate (2 × 100 mL). The crude material was adsorbed onto Isolute and purified by flash column chromatography (silica gel, 80 g, 0% to 100% ethyl acetate in heptane). Evaporation of product-containing fractions gave the title compound (1.561 g, 2.63 mmol, 82.2%). MS(m / e):595.4(M+H).
[0207] Step 4: tert-Butyl N-[2-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate
[0208] A mixture of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)-1H-pyrazole (29 mg, 105 μmol), tert-butyl N-[2-[2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]ethoxy]ethyl]carbamate (41.6 mg, 70 μmol), NaCO (14.8 mg, 140 μmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane adduct (5.72 mg, 7 μmol) in dioxane (1 mL) / water (100 μL) was stirred overnight at 110° C. The reaction mixture was poured into 4 mL of water, extracted with ethyl acetate (2 × 5 mL), and concentrated. The title compound was used in the next step without further purification. MS (m / e): 617.4 (M+H).
[0209] Step 5: N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0210] tert-Butyl N-[2-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate (crude) was dissolved in DCM (2 mL), treated with excess HCl in dioxane (525 μL, 4N), and stirred at room temperature overnight. The mixture was evaporated, dissolved in DMF, and purified by reverse-phase column chromatography eluting with a gradient formed from acetonitrile / water / trimethylamine. Evaporation of product-containing fractions afforded the title compound (5.2 mg, 14% over two steps). MS (m / e): 517.4 (M+H).
[0211] Example 2 N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide [ka]
[0212] Step 1: tert-Butyl N-[2-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate
[0213] Using a procedure similar to that described for the synthesis of tert-butyl N-[2-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate (Example 1, Step 4), the title compound was prepared from tert-butyl N-[2-[2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]ethoxy]ethyl]carbamate and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid as a pale yellow oil. MS (m / e): 603.3 (M+H).
[0214] Step 2: tert-Butyl N-[2-[2-[[2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate
[0215] A mixture of tert-butyl N-[2-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate (40.1 mg, 56.5 μmol), potassium carbonate (19.5 mg, 141 μmol), and 4-(bromomethyl)pyrimidine hydrobromide (21.5 mg, 84.7 μmol) in DMF (2 mL) was stirred overnight at room temperature and heated to 70 °C. After cooling, the mixture was poured into water (15 mL) and extracted with ethyl acetate (2 × 15 mL). The combined organic layers were dried over MgSO and evaporated. The crude title compound was used in the next step without further purification. MS (m / e): 695.3 (M+H).
[0216] Step 3: N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0217] A mixture of tert-butyl N-[2-[2-[[2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate and TFA (0.15 mL) in DCM (2 mL) was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was purified by reverse-phase column chromatography eluting with a gradient formed from acetonitrile / water / trimethylamine, and the product-containing fractions were evaporated to give the title compound (5.2 mg, 15% over two steps). MS (m / e): 595.2 (M+H).
[0218] Example 3 (2S)-N-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide [ka]
[0219] Step 1: Methyl 2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoate
[0220] Using a procedure similar to that described for the synthesis of tert-butyl N-[2-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate (Example 1, Step 4), the title compound was prepared from methyl 2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoate and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid as a pale red solid. MS (m / e): 433.3 (M+H).
[0221] Step 2: 2-Ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid, hydrochloride
[0222] The title compound was prepared from methyl 2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoate as a pale gray solid using a procedure similar to that described for the synthesis of 2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid (Example 1, Step 2). MS (m / e): 417.2 (M+H).
[0223] Step 3: tert-Butyl N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]carbamate
[0224] A mixture of 2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoic acid hydrochloride (1.343 g, 2.97 mmol) was dissolved in DMF (15.3 mL). N-Ethyl-N-isopropylpropan-2-amine (1.92 g, 2.52 mL, 14.8 mmol), tert-butyl (2-aminoethyl)carbamate CAS [57260-73-8] (570 mg, 3.56 mmol), and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl-1,1,3,3-tetramethylisouronium hexafluorophosphate (V) (HATU) (2.26 g, 5.93 mmol) were added, and the yellow solution was stirred at room temperature for 1 h. The solvent was evaporated, and the crude material was purified by flash chromatography (silica gel, 100 g, 0% to 100% Purification by DCM / MeOH / NH4OH (90 / 10 / 1) was performed. The product-containing fractions were evaporated to give the title compound as a brown solid (2.324 g, 70% purity), which was used in the next step without further purification. MS (m / e): 559.4 (M+H).
[0225] Step 4: N-(2-aminoethyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0226] The title compound was prepared from tert-butyl N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl)]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]carbamate in a manner similar to that described for the synthesis of N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide (Example 2, Step 3). MS (m / e): 459.3 (M+H).
[0227] Step 5: tert-Butyl (2S)-2-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethylcarbamoyl]pyrrolidine-1-carboxylate;
[0228] A mixture of N-(2-aminoethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide (660 mg, 1.44 mmol) was dissolved in DMF (9 mL). N-ethyl-N-isopropylpropan-2-amine (930 mg, 1.22 mL, 7.2 mmol), (tert-butoxycarbonyl)-L-proline CAS [15761-39-4] (372 mg, 1.73 mmol), and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate (V) (HATU) (1.09 g, 2.88 mmol) was added, and the yellow solution was stirred at room temperature for 1.5 hours. The solvent was evaporated and the crude material was purified by flash chromatography (silica gel, 100 g, 0% to 100% DCM / MeOH / NH4OH (90 / 10 / 1)). Evaporation of product-containing fractions afforded the title compound as a white foam (1 g, 96% purity), which was used in the next step without further purification. MS (m / e): 656.4 (M+H).
[0229] Step 6: tert-Butyl (2S)-2-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]ethylcarbamoyl]pyrrolidine-1-carboxylate
[0230] Analogously to the alkylation procedure described for the synthesis of tert-butyl N-[2-[2-[[2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate (Example 2, Step 2), the title compound was prepared from tert-butyl (2S)-2-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethylcarbamoyl]pyrrolidine-1-carboxylate and 2-bromoacetonitrile [CAS#590-17-0]. MS (m / e): 695.5 (M+H).
[0231] Step 7: (2S)-N-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide
[0232] The title compound was synthesized from tert-butyl (2S)-2-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]ethylcarbamoyl]pyrrolidine-1-carboxylate and TFA using a deprotection procedure similar to that described for the synthesis of N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide (Example 2, Step 3). MS (m / e): 594.6 (M+H).
[0233] Example 4 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide [ka]
[0234] Step 1: 8-chloro-3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazine
[0235] A mixture of 8-chloro-3-iodoimidazo[1,2-a]pyrazine (3 g, 10.7 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)-1H-pyrazole (3.38 g, 12.9 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane adduct (877 mg, 1.07 mmol) and NaCO (2.28 g, 21.5 mmol) in dioxane (107 mL) / water (10.7 mL) was stirred at 105 °C for 5 h. The crude material was absorbed onto Isolute HM-N, dried, and purified by flash chromatography to give 8-chloro-3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazine as an off-white solid (1.76 g, 6.12 mmol, 57% yield). MS (m / e): 288.2 (M+H).
[0236] Step 2: Methyl 2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoate
[0237] A mixture of methyl 4-amino-2-fluoro-6-methylbenzoate (856 mg, 4.67 mmol) and 8-chloro-3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazine (1.583 g, 4.68 mmol) in acetonitrile (16 mL) and acetic acid (1.6 mL) was stirred at 120° C. for 4.5 hours. The mixture was cooled to ambient temperature. The crude material was absorbed onto Isolute HM-N, dried, and purified by flash chromatography to give methyl 2-fluoro-6-methyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoate (1.833 g, 3.88 mmol, 83.1% yield) as an off-white solid. MS(m / e):435.2(M+H).
[0238] Step 3: 2-Fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid
[0239] A mixture of methyl 2-fluoro-6-methyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoate (1.83 g, 4.21 mmol) in water (20 mL), MeOH (5 mL), and KOH (5 M aqueous solution) (3 mL, 15 mmol) was stirred at 70 °C for 3.5 h. The organic solvent was removed in vacuo. The solution was diluted with water, and an aqueous solution of acetic acid (901 mg, 859 μL, 15 mmol) was added dropwise with stirring at 40 °C. The white suspension was cooled to ambient temperature, filtered off, and the white crystals were washed with water (2 × 15 mL, 5 °C) and dried under vacuum to give 2-fluoro-6-methyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoic acid (1.685 g, 3.65 mmol, 86.6% yield) as white crystals. MS (m / e): 419.3 (MH).
[0240] Step 4: 2-Fluoro-6-methyl-N-prop-2-ynyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide (Example 43)
[0241] The title compound was prepared from 2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid and prop-2-yn-1-amine similarly to the amide coupling procedure described for the synthesis of Example 1, Step 3. MS (m / e): 458.2 (M+H).
[0242] Step 5: 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide
[0243] Analogously to the alkylation procedure described for the synthesis of Example 2, Step 2, the title compound was prepared from 2-fluoro-6-methyl-N-prop-2-ynyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide and 2-bromoacetonitrile. MS (m / e): 497.2 (MH).
[0244] Example 5 [2-Ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone [ka]
[0245] Step 1: tert-Butyl 4-[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]piperazine-1-carboxylate
[0246] The title compound was prepared from 2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid, hydrochloride, and tert-butyl piperazine-1-carboxylate in a manner similar to that described for Example 1, Step 3. MS (m / e): 577.4 (M+H).
[0247] Step 2: [2-Ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]phenyl]-piperazin-1-yl)methanone hydrochloride The title compound was prepared by a procedure similar to that described for Example 1, Step 5, from tert-butyl 4-[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]piperazine-1-carboxylate
[0248] and prepared from tert-butyl piperazine-1-carboxylate via Boc group cleavage with HCl.
[0249] Step 3: tert-Butyl 4-[4-[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate
[0250] The title compound was prepared from [2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]phenyl]-piperazin-1-yl-methanone, hydrochloride, and 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid in a manner similar to that described in Example 1, Step 3. MS (m / e): 588.6 (M+H).
[0251] Step 4: tert-Butyl 4-[4-[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate
[0252] Analogously to the procedure described in Example 1, Step 4, the title compound was prepared from tert-butyl 4-[4-[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid. MS (m / e): 696.7 (M+H).
[0253] Step 5: tert-Butyl 4-[4-[2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate
[0254] The title compound was prepared from tert-butyl 4-[4-[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate and 3-bromoprop-1-yne in a similar manner to the procedure described in Example 2, Step 2. MS (m / e): 734.6 (M+H).
[0255] Step 6: [2-Ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone
[0256] Similarly to the procedure described for Example 2, Step 3, the title compound was prepared from tert-butyl 4-[4-[2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carbonyl]piperidine-1-carboxylate via TFA cleavage of the Boc group. MS (m / e): 634.4 (M+H).
[0257] Example 6 2-Amino-1-[4-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone [ka]
[0258] Step 1: Methyl 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoate
[0259] The title compound was prepared from 8-chloro-3-iodoimidazo[1,2-a]pyrazine and methyl 4-amino-2-chloro-benzoate in a manner similar to that described in Example 1, Step 1. MS (m / e): 429.2 (M+H).
[0260] Step 2: Methyl 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoate
[0261] The title compound was prepared from methyl 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoate and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid in a manner similar to that described in Example 1, Step 4. MS (m / e): 437.2 (M+H).
[0262] Step 3: 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid
[0263] The title compound was prepared from methyl 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoate by a procedure similar to that described in Example 1, Step 2. MS (m / e): 423.1 (M+H).
[0264] Step 4: tert-Butyl 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate
[0265] The title compound was prepared from 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid and tert-butyl piperazine-1-carboxylate in a manner similar to that described for Example 1, Step 3. MS (m / e): 591.2 (M+H).
[0266] Step 5: [2-Chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-yl-methanone
[0267] The title compound was prepared from tert-butyl 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate in a manner similar to that described for Example 1, Step 5. MS (m / e): 491.2 (M+H).
[0268] Step 6: tert-Butyl N-[2-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]-2-oxoethyl]carbamate
[0269] The title compound was prepared from [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-yl-methanone and (tert-butoxycarbonyl)glycine CAS [4530-20-5] in a manner similar to that described for Example 5, Step 3. MS (m / e): 648.4 (M+H).
[0270] Step 7: tert-Butyl N-[2-[4-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]-2-oxo-ethyl]carbamate
[0271] Analogously to the procedure described in Example 2, Step 2, the title compound was prepared from tert-butyl N-[2-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]-2-oxo-ethyl]carbamate and 1,1-difluoro-2-iodo-ethane. MS (m / e): 712.5 (M+H).
[0272] Step 8: The title compound was prepared from tert-butyl N-[2-[4-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]-2-oxo-ethyl]carbamate in a manner similar to that described for Example 2, Step 3. MS (m / e): 612.3 (M+H).
[0273] Example 7 N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-(pyridin-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide hydrochloride [ka]
[0274] Step 1: Step 1: tert-Butyl N-[3-(tert-butoxycarbonylamino)propyl-N-[4-[tert-butoxycarbonyl-[3-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]propyl]amino]butyl]carbamate
[0275] Analogously to the procedure described for Example 1, Step 3, the title compound was prepared from 2-ethyl-4-((3-iodoimidazo[1,2-a]pyrazin-8-yl)amino)benzoic acid hydrochloride and tert-butyl(3-aminopropyl)(4-((tert-butoxycarbonyl)(3-((tert-butoxycarbonyl)amino)propyl)amino)butyl)carbamate. MS (m / e): 893.8 (M+H).
[0276] Step 2: tert-Butyl N-[3-(tert-butoxycarbonylamino)propyl]-N-[4-[tert-butoxycarbonyl-[3-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]propyl]amino]butyl]carbamate
[0277] Analogously to the procedure described for Example 1, step 4, the title compound was prepared from tert-butyl N-[3-(tert-butoxycarbonylamino)propyl]-N-[4-[tert-butoxycarbonyl-[3-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino)benzoyl]amino]propyl]amino]butyl]carbamate and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid. MS (m / e): 899.8 (MH).
[0278] Step 3: tert-Butyl N-[3-(tert-butoxycarbonylamino)propyl]-N-[4-[tert-butoxycarbonyl-[3-[[2-ethyl-4-[[3-[1-(3-pyridylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]propyl]amino]butyl]carbamate
[0279] Similarly to the procedure described for Example 2, Step 2, the title compound was prepared from tert-butyl N-[3-(tert-butoxycarbonylamino)propyl-N-{4-tert-butoxycarbonyl-[3-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]amino]butyl]carbamate and 3-(chloromethyl)pyridine hydrochloride. MS (m / e): 992.8 (M+H).
[0280] Step 4: N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-(pyridin-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide hydrochloride
[0281] The title compound was prepared from tert-butyl N-[3-(tert-butoxycarbonylamino)propyl-N-[4-tert-butoxycarbonyl-[3-[[2-ethyl-4-[[3-[1-(3-pyridylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]amino]butyl]carbamate in a manner similar to that described for Example 1, Step 5. MS (m / e): 692.4 (M+H).
[0282] Example 8 N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate [ka]
[0283] Step 1: Ethyl 2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetate
[0284] The title compound was prepared from 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid and glycine ethyl ester hydrochloride in a manner similar to that described for Example 1, Step 3. MS (m / e): 508.3 (M+H).
[0285] Step 2: 2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetic acid
[0286] To a solution of ethyl 2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetate (3.5 g, 6.89 mmol) in THF (20 mL) / methanol (20 mL) was added aqueous sodium hydroxide (40.0 mL, 40 mmol) and stirred at 20 °C for 3 h. The mixture was concentrated, and the aqueous layer was washed with ethyl acetate (30 mL) and then adjusted to pH 1-2 with 3N HCl. The precipitate was filtered and dried to give the title compound as an off-white solid (3.2 g, 6.67 mmol, 96.8%). MS (m / e): 480.1 (M+H).
[0287] Step 3: tert-Butyl N-[2-[[2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetyl]amino]ethyl]carbamate
[0288] The title compound was prepared from 2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetic acid and N-BOC-ethylenediamine in a manner similar to that described for Example 5, Step 3. MS (m / e): 622.1 (M+H).
[0289] Step 4: tert-Butyl N-[2-[[2-[[2-chloro-4-[[3-[1-(2-fluoroethyl)-[3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetyl]amino]ethyl]carbamate
[0290] Similarly to the procedure described for Example 2, Step 2, the title compound was prepared from tert-butyl N-[2-[[2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetyl]amino]ethyl]carbamate and 1-bromo-2-fluoroethane. MS (m / e): 668.3 (M+H).
[0291] Step 5: N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate
[0292] Similarly to the procedure described for Example 2, Step 3, the title compound was prepared from tert-butyl N-[2-[[2-[[2-chloro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]acetyl]amino]ethyl]carbamate and TFA. MS (m / e): 568.1 (M+H).
[0293] Example 9 [2-Chloro-4-[difluoromethyl[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone [ka]
[0294] Step 1: tert-Butyl 4-[2-chloro-4-[difluoromethyl-[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate
[0295] A mixture of tert-butyl 4-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carboxylate (Example 6, Step 4) (200 mg, 338 μmol), sodium bicarbonate [CAS#144-55-8] (85.3 mg, 1.02 mmol), and methyl 2-chloro-2,2-difluoroacetate [CAS#1514-87-0] (97.8 mg, 677 μmol) in DMF (3 mL) was heated in a microwave at 120° C. for 10 minutes. The crude reaction mixture was purified by reverse-phase flash chromatography eluting with a gradient formed from acetonitrile and water. Evaporation of product-containing fractions gave the title compound (52 mg, 16%). MS (m / e): 641.3 (M+H).
[0296] Step 2: [2-Chloro-4-[difluoromethyl[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone
[0297] Analogously to the procedure described for Example 2, Step 3, the title compound was prepared from tert-butyl 4-[2-chloro-4-[difluoromethyl-[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate via TFA cleavage of the Boc group. MS (m / e): 541.3 (M+H).
[0298] Example 10 2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide [ka]
[0299] Step 1: 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-N-methyl-benzamide
[0300] A mixture of 8-chloro-3-iodoimidazo[1,2-a]pyrazine (2 g, 7.16 mmol) and 4-amino-2-chloro-N-methylbenzamide [CAS#926203-17-0] (1.32 g, 7.16 mmol) in acetonitrile (13 mL) and glacial acetic acid (1.3 mL) was heated in a microwave at 120 °C for 30 minutes. The reaction mixture was diluted with acetonitrile, filtered, and the precipitate was washed with acetonitrile (25 mL). The solid was suspended in acetonitrile / water, frozen to -78 °C, and lyophilized to give the title compound as a yellow solid (2.83 g, 87%). MS (m / e): 428.1 (M+H).
[0301] Step 2: 2-Chloro-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0302] The title compound was prepared from 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]N-methyl-benzamide and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid in a manner similar to that described in Example 1, Step 4. MS (m / e): 428.1 (M+H).
[0303] Step 3: 2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide
[0304] The title compound was prepared from 2-chloro-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[[1,2-a]pyrazin-8-yl]amino]benzamide and methyl 2-chloro-2,2-difluoroacetate in a manner similar to that described for Example 2, Step 2. MS (m / e): 468.3 (M+H).
[0305] Example 11 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-3-[(3S)-pyrrolidin-3-yl]urea [ka]
[0306] Step 1: tert-Butyl N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-4-piperidyl]carbamate
[0307] The title compound was prepared from 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid and tert-butyl piperazine-1-carboxylate in a manner similar to that described for Example 1, Step 3. MS (m / e): 605.4 (M+H).
[0308] Step 2: (4-Amino-1-piperidyl)-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone
[0309] Analogously to the procedure described in Example 1, Step 5, the title compound was prepared from tert-butyl N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-4-piperidyl]carbamate via Boc deprotection with HCl. MS (m / e): 505.4 (M+H).
[0310] Step 3: tert-Butyl 3-[[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-4-piperidyl]carbamoylamino]pyrrolidine-1-carboxylate
[0311] A mixture of (4-aminopiperidin-1-yl)(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone (0.15 g, 297 μmol), N-ethyl-N-isopropylpropan-2-amine (192 mg, 253 μl, 1.49 mmol), and triphosgene CAS [32315-10-9] (35.3 mg, 119 μmol) was suspended in DCM (5.99 mL) and stirred at 0° C. for 1 hour. A solution of tert-butyl (S)-3-aminopyrrolidine-1-carboxylate [CAS #147081-44-5] (166 mg, 891 μmol) in DCM (2.39 mL) was added, and the reaction mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with DCM. The combined organic layers were dried over MgSO, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 20 g, 0% to 100% DCM / MeOH / NHOH (90 / 10 / 1)). The compound was purified a second time to give, after evaporation of the product-containing fractions, the title compound (0.1 g, 48%) as a colorless gum. MS (m / e): 717.5 (M+H).
[0312] Step 4: tert-Butyl 3-[[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-4-piperidyl]carbamoylamino]pyrrolidine-1-carboxylate
[0313] The title compound was prepared from tert-butyl 3-[[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-4-piperidyl]carbamoylamino]pyrrolidine-1-carboxylate and 2-bromoacetonitrile [CAS#590-17-0] in a similar manner to the procedure described in Example 2, Step 2. MS (m / e): 756.7 (M+H).
[0314] Step 5: 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-3-[(3S)-pyrrolidin-3-yl]urea
[0315] Analogously to the procedure described in Example 2, Step 3, the title compound was prepared from tert-butyl 3-[[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-4-piperidyl]carbamoylamino]pyrrolidine-1-carboxylate via Boc deprotection with TFA. MS (m / e): 656.5 (M+H).
[0316] Example 12 2-[4-[8-[4-[4-(3-aminocyclobutanecarbonyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate [ka]
[0317] Step 1: tert-Butyl 4-[2-chloro-4-[[3-[1-(cyanomethyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate
[0318] The title compound was prepared from tert-butyl 4-[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]piperazine-1-carboxylate and 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile in a manner similar to that described in Example 1, Step 4. MS (m / e): 630.2 (M+H).
[0319] Step 2: 2-[4-[8-[3-chloro-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile
[0320] Analogously to the procedure described in Example 2, Step 3, the title compound was prepared from tert-butyl 4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate via Boc deprotection with TFA. MS (m / e): 530.1 (M+H).
[0321] Step 3: tert-Butyl N-[3-[4-[2-chloro-4-[[3-[1-(cyanomethyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carbonyl]cyclobutyl]carbamate
[0322] Similarly to the procedure described for Example 5, Step 3, the title compound was prepared from 2-[4-[8-[3-chloro-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile and 3-(tert-butoxycarbonylamino)cyclobutanecarboxylic acid. MS (m / e): 727.3 (M+H).
[0323] Step 4: 2-[4-[8-[4-[4-(3-aminocyclobutanecarbonyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate
[0324] Analogously to the procedure described in Example 2, Step 3, the title compound was prepared from tert-butyl N-[3-[4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carbonyl]cyclobutyl]carbamate via Boc deprotection with TFA. MS (m / e): 627.0 (M+H).
[0325] Example 13 N-[3-[[(2S)-2-Amino-3-carbamimidamidopropanoyl]amino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate [ka]
[0326] Step 1: tert-Butyl N-[3-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]propyl]carbamate
[0327] The title compound was prepared from 2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid, hydrochloride, and N-BOC-1,3-diaminopropane in a manner similar to that described for Example 1, Step 3. MS (m / e): 565.2 (M+H).
[0328] Step 2: tert-Butyl N-[3-[[2-ethyl-4-[[3-[1-[(4-methoxyphenyl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]carbamate
[0329] Analogously to the procedure described in Example 1, Step 4, the title compound was prepared from tert-butyl N-[3-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]propyl]carbamate and 1-[(4-methoxyphenyl)methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyrazole. MS (m / e): 693.4 (M+H).
[0330] Step 3: N-(3-aminopropyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0331] To a solution of tert-butyl N-[3-[[2-ethyl-4-[[3-[1-[(4-methoxyphenyl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]carbamate (680.0 mg, 0.980 mmol) in trifluoroacetic acid (5.0 mL, 64.9 mmol) was added trifluoromethanesulfonic acid (1.47 g, 9.82 mmol). The reaction was stirred at 80 °C for 2 hours. The reaction mixture was concentrated and adjusted to pH = 7 with triethylamine. The residue was purified by preparative HPLC. The product-containing fractions were lyophilized to afford the title compound as a white solid (400 mg, 0.850 mmol, 86.3% yield). MS (m / e): 473.2 (M+H).
[0332] Step 4: tert-Butyl N-[(1S)-2-[3-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propylamino]-1-(guanidinomethyl)-2-oxo-ethyl]carbamate
[0333] Similarly to the procedure described for Example 5, Step 3, the title compound was prepared from N-(3-aminopropyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide and (2S)-2-(tert-butoxycarbonylamino)-3-guanidino-propanoic acid. MS (m / e): 701.2 (M+H).
[0334] Step 5: N-[3-[[(2S)-2-Amino-3-carbamimidamidopropanoyl]amino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide formate
[0335] Analogously to the procedure described for Example 2, step 3, the title compound was prepared from tert-butyl N-[(1S)-2-[3-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propylamino]-1-(guanidinomethyl)-2-oxo-ethyl]carbamate via Boc deprotection with TFA. MS (m / e): 601.3 (M+H).
[0336] Example 14 2-[4-[8-[3-chloro-4-[4-hydroxy-4-(methylaminomethyl)piperidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate [ka]
[0337] Step 1: 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid
[0338] To a solution of methyl 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoate (25.0 g, 58.33 mmol) (Example 6, Step 1) in THF (125 mL) / methanol (125 mL) was added aqueous sodium hydroxide (125.0 mL, 250 mmol) and stirred at 60° C. for 12 h. The cooled reaction mixture was adjusted to pH=1-2 with 3N HCl, filtered, and evaporated to give the crude title compound as a white solid (25 g). MS (m / e): 414.8 (M+H).
[0339] Step 2: 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid
[0340] The title compound was prepared from 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid and 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile in a manner similar to that described in Example 1, Step 4. MS (m / e): 462.1 (M+H).
[0341] Step 3: 2-[4-[8-[3-chloro-4-[4-hydroxy-4-(methylaminomethyl)piperidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile
[0342] Similarly to the procedure described for Example 1, Step 3, the title compound was prepared from 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoic acid and tert-butyl N-[(4-hydroxy-4-piperidyl)methyl]-N-methyl-carbamate. MS (m / e): 688.3 (M+H).
[0343] Step 4: 2-[4-[8-[3-chloro-4-[4-hydroxy-4-(methylaminomethyl)piperidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile formate
[0344] To a solution of tert-butyl N-[[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-4-hydroxy-4-piperidyl]methyl]-N-methyl-carbamate (25.0 mg, 0.040 mmol) in DCM (4.9 mL) was added 2,6-lutidine (0.01 mL, 0.070 mmol) and trimethylsilyl trifluoromethanesulfonate (20.19 mg, 0.090 mmol) at 0 °C, and the mixture was stirred at 25 °C for 0.5 h. The reaction mixture was diluted with NH · The pH was adjusted to 7 with HO (aq) and evaporated. The residue was purified by preparative HPLC to give, after evaporation of the product-containing fractions, the title compound as an off-white solid acid (12.8 mg, 55.6%). MS (m / e): 588.1 (M+H).
[0345] Example 15 2-Ethyl-N-methyl-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide [ka]
[0346] Step 1: 2-Ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-N-methyl-benzamide
[0347] The title compound was prepared from 2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid, hydrochloride (Example 1, Step 2) and methylamine as an off-white solid, similar to the procedure described for the synthesis of Example 1, Step 3. MS (m / e): 422.1 (M+H).
[0348] Step 2: 2-Ethyl-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0349] Similarly to the procedure described in Example 1, Step 4, the title compound was prepared from 2-chloro-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid [CAS#1202054-12-3] as a brown solid. MS (m / e): 430.3 (M+H).
[0350] Step 3: 2-Ethyl-N-methyl-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0351] A mixture of 2-ethyl-N-methyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide (50 mg, 116 μmol), (1H-pyrazol-3-yl)methanol [CAS#23585-49-1] (13.7 mg, 140 μmol), tributylphosphine [CAS#998-40-3] (70.7 mg, 86 μL, 349 μmol), and ADDP [CAS#10465-81-3] (88.1 mg, 349 μmol) in DMF (1 mL) was stirred at room temperature for 1 h. The mixture was extracted with ethyl acetate and water (pH 8-9). The organic layer was dried over magnesium sulfate, and the solvent was evaporated. The crude material was purified by flash chromatography (silica gel, 20 g, 0% to 50% DCM / MeOH / NH4OH (95 / 5 / 1)). The mixed fraction (50 mg) was purified by reverse phase under basic conditions to give the title compound as a white solid (20 mg, 34%). MS (m / e): 510.4 (M+H).
[0352] Example 16 N-[2-(2-aminoethoxy)ethyl]-2-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide [ka]
[0353] Step 1: 4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoic acid
[0354] The title compound was prepared from 3-chloro-3-iodoimidazo[1,2-a]pyrazine and 4-amino-2-methylbenzoic acid as a white solid in a manner similar to that described in Example 1, Step 1. MS (m / e): 395.1 (M+H).
[0355] Step 2: tert-Butyl N-[2-[2-[[4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoyl]amino]ethoxy]ethyl]carbamate
[0356] The title compound was prepared from 4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoic acid and tert-butyl (2-(2-aminoethoxy)ethyl)carbamate in a manner similar to that described for Example 1, Step 3. MS (m / e): 581.3 (M+H).
[0357] Step 3: tert-Butyl N-[2-[2-[[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate
[0358] Analogously to the procedure described in Example 1, Step 4, the title compound was prepared from tert-butyl N-[2-[2-[[4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoyl]amino]ethoxy]ethyl]carbamate and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid. MS (m / e): 589.4 (M+H).
[0359] Step 4: N-[2-(2-aminoethoxy)ethyl]-2-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide
[0360] Analogously to the procedure described in Example 1, Step 5, the title compound was prepared from tert-butyl N-[2-[2-[[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethoxy]ethyl]carbamate and 3-bromoprop-1-yne, followed by acidic Boc deprotection. MS (m / e): 527.5 (M+H).
[0361] Example 17 [4-(3-Aminocyclobutanecarbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate [ka]
[0362] Step 1: tert-Butyl 4-[4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoyl]piperazine-1-carboxylate
[0363] The title compound was prepared from 4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoic acid (Example 16, Step 1) and Boc-piperazine in a similar manner to the procedure described in Example 1, Step 3. MS (m / e): 563.0 (M+H).
[0364] Step 2: tert-Butyl 4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate
[0365] The title compound was prepared from tert-butyl 4-[4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoyl]piperazine-1-carboxylate and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid in a manner similar to that described in Example 1, Step 4. MS (m / e): 571.3 (M+H).
[0366] Step 3: [2-Methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-yl-methanone
[0367] The title compound was prepared from tert-butyl 4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxylate by acidic Boc deprotection similar to the procedure described for Example 1, Step 5. MS (m / e): 471.3 (M+H).
[0368] Step 4: tert-Butyl N-[2-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]-2-oxoethyl]carbamate
[0369] The title compound was prepared from [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-yl-methanone and (tert-butoxycarbonyl)glycine in a manner similar to that described for Example 5, Step 3. MS (m / e): 628.5 (M+H).
[0370] Step 5: [4-(3-Aminocyclobutanecarbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone formate
[0371] Analogously to the procedure described for Example 1, step 5, the title compound was prepared from tert-butyl N-[2-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]-2-oxo-ethyl]carbamate by acidic Boc deprotection. MS (m / e): 528.4 (M+H).
[0372] Example 18 N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide [ka]
[0373] Step 1: tert-Butyl N-[2-[2-[[4-[[3-[3-(difluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]ethoxy]ethyl]carbamate
[0374] Analogously to the procedure described in Example 1, Step 4, the title compound was prepared from tert-butyl N-[2-[2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]ethoxy]ethyl]carbamate (Example 1, Step 3) and 3-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. MS (m / e): 585.4 (M+H).
[0375] Step 2: tert-Butyl N-[2-[2-[[4-[[3-[1-(cyanomethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]ethoxy]ethyl]carbamate
[0376] The title compound was prepared from tert-butyl N-[2-[2-[[4-[[3-[3-(difluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]ethoxy]ethyl]carbamate and 2-bromoacetonitrile [CAS#590-17-0] in a manner similar to that described for Example 2, Step 2. MS (m / e): 624.4 (M+H).
[0377] Step 3: N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide
[0378] The title compound was prepared from tert-butyl N-[2-[2-[[4-[[3-[1-(cyanomethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]ethoxy]ethyl]carbamate by acidic Boc deprotection similar to the procedure described for Example 1, step 5. MS (m / e): 524.4 (M+H).
[0379] Example 19 2-[4-[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]piperazin-1-yl]ethyl-trimethylazanium formate [ka]
[0380] Step 1: 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzoic acid
[0381] The title compound was prepared from 4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]-2-methyl-benzoic acid (Example 16, Step 1) and (3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid in a similar manner to the procedure described in Example 1, Step 4. MS (m / e): 442.0 (M+H).
[0382] Step 2: 2-[4-[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]piperazin-1-yl]ethyl-trimethylazanium formate
[0383] The title compound was prepared from 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzoic acid and trimethyl(2-piperazin-1-ylethyl)ammonium chloride in a manner similar to that described for Example 1, Step 3. MS (m / e): 595.2 (M+H).
[0384] Example 20 N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-(methoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide [ka]
[0385] Step 1: 4-Bromo-3-(difluoromethyl)-1-(methoxymethyl)pyrazole
[0386] To a solution of 4-bromo-3-(difluoromethyl)-1H-pyrazole (250 mg, 1.27 mmol, CAS 1451392-65-6) and potassium carbonate (351 mg, 2.54 mmol) in DMF (8 mL) was added iodo(methoxy)methane (262 mg, 129 μL, 1.52 mmol) and stirred overnight at 22 °C under argon. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (2 × 50 mL). The organic layers were combined, adsorbed onto Isolute, and purified by flash chromatography (silica gel, 12 g, 0% to 60% TBME) to afford, after evaporation of the product-containing fractions, the title compound as a colorless liquid (142 mg, 46%). MS (m / e): 243.0 (M+H).
[0387] Step 2: 3-(Difluoromethyl)-1-(methoxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole
[0388] 4-Bromo-3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazole (142 mg, 589 μmol) was dissolved in dry THF (15 mL) under argon. The mixture was cooled to −78°C. N-butyllithium (442 μL, 707 μmol) was added dropwise, and the mixture was stirred at −78°C for 40 minutes. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (164 mg, 180 μL, 884 μmol) was added dropwise. After completion of the reaction, the mixture was poured into saturated NH₄Cl (25 mL) and extracted with ethyl acetate (2 × 15 mL). The crude material was adsorbed onto Isolute and purified by flash column chromatography (silica gel, SiliCycle 10 g cartridge (40–63 μm), 0%–100% MTBE in heptane). The two regioisomers, 3-(difluoromethyl)-1-(methoxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 3-(difluoromethyl)-1-(methoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (72.7 mg, 21%), were formed and used in the subsequent step without further purification. MS (m / e): 289.3 (M+H).
[0389] Step 3: tert-Butyl N-[2-[2-[[4-[[3-[3-(difluoromethyl)-1-(methoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]ethoxy]ethyl]carbamate
[0390] Analogously to the procedure described in Example 1, Step 4, the title compound was prepared from tert-butyl N-[2-[2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]ethoxy]ethyl]carbamate (Example 1, Step 3) and 3-(difluoromethyl)-1-(methoxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (regioisomeric mixture from Example 20, Step 2). MS (m / e): 629.3 (M+H).
[0391] Step 4: 2-[4-[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]piperazin-1-yl]ethyl-trimethylazanium formate
[0392] Analogously to the procedure described for Example 1, step 5, the title compound was prepared from tert-butyl N-[2-[2-[[4-[[3-[3-(difluoromethyl)-1-(methoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]ethoxy]ethyl]carbamate by acidic Boc deprotection. MS (m / e): 529.3 (M+H).
[0393] The following examples were synthesized similarly to the procedures described above. The reaction sequences and starting materials are recorded in Table 1. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16 Table 1-17 Table 1-18 Table 1-19 Table 1-20 Table 1-21 Table 1-22 Table 1-23 Table 1-24 Table 1-25 Table 1-26 Table 1-27 Table 1-28 Table 1-29 Table 1-30 Table 1-31 Table 1-32 Table 1-33 Table 1-34 Table 1-35 Table 1-36 Table 1-37 Table 1-38 Table 1-39 Table 1-40 Table 1-41 Table 1-42 Table 1-43 Table 1-44 Table 1-45 Table 1-46 Table 1-47 Table 1-48 Table 1-49 Table 1-50 Table 1-51 Table 1-52 Table 1-53 Table 1-54 Table 1-55 Table 1-56 Table 1-57 Table 1-58 Table 1-59 Table 1-60 Table 1-61 Table 1-62 Table 1-63 Table 1-64 Table 1-65 Table 1-66 Table 1-67 Table 1-68 Table 1-69 Table 1-70 Table 1-71 Table 1-72 Table 1-73 Table 1-74 Table 1-75 Table 1-76 Table 1-77 Table 1-78 Table 1-79 Table 1-80 Table 1-81 Table 1-82 Table 1-83 Table 1-84 Table 1-85 Table 1-86 Table 1-87 Table 1-88 Table 1-89
Table 1-90
Table 1-100
Table 1-110
Table 1-120
[0394] Example 481 2-(4-(8-((4-(4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate [ka]
[0395] Step 1: tert-Butyl (1R,5S,6r)-6-(4-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carbonyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate
[0396] The title compound was prepared from [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-yl-methanone (Example 6, Step 5) and (1R,5S,6r)-3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid CAS [927679-54-7] in a manner similar to that described in Example 3, Step 5. MS (m / e): 700.4 (M+H).
[0397] Step 2: tert-Butyl (1R,5S,6r)-6-(4-(2-chloro-4-((3-(1-(cyanomethyl)-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carbonyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate
[0398] To a microwave vial was added tert-butyl (1R,5S,6r)-6-(4-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carbonyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (40 mg, 57.1 μmol), 2-bromoacetonitrile CAS[590-17-0] (13.7 mg, 114 μmol), and sodium bicarbonate CAS[144-55-8] (14.4 mg, 171 μmol) in DMF (0.5 ml). The vial was capped and heated in a microwave at 120° C. for 15 minutes. The crude reaction mixture was purified by preparative HPLC. The relevant fractions were combined, frozen at -78°C, and then lyophilized overnight to remove the solvent, affording the title compound as a white lyophilized solid (33 mg, 42.4 μmol, 74.2% yield). MS (m / e): 739.4 (M+H).
[0399] Step 3: 2-(4-(8-((4-(4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile formate
[0400] tert-Butyl (1R,5S,6r)-6-(4-(2-chloro-4-((3-(1-(cyanomethyl)-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carbonyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (33 mg, 44.6 μmol) was combined with DCM (2 ml) to give a colorless solution. TFA CAS[76-05-1] (102 mg, 68.8 μl, 893 μmol) was added and the reaction mixture was stirred at 20 °C overnight. The reaction mixture was quenched by the addition of DCM / MeOH / NH3 (95 / 5 / 1) until the pH was basic. The solvent was then completely evaporated. The crude product was purified by preparative HPLC (1% to 100% acetonitrile in water (+0.1% The product was purified by HCl (HCOOH). The relevant fractions were combined, frozen at -78 °C, and then lyophilized overnight to remove the solvent, affording the title compound as a white lyophilized solid (26 mg, 32.6 μmol, 73.1% yield). MS (m / e): 683.4 (M+HCOO)-.
[0401] Example 482 N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate [ka]
[0402] Step 1: tert-Butyl (3-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)carbamate
[0403] The title compound was prepared from 2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]benzoic acid, hydrochloride (Example 3, Step 2) and tert-butyl (3-aminopropyl)carbamate CAS [75178-96-0] using an amide coupling procedure similar to that described for the synthesis of tert-butyl N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]carbamate (Example 3, Step 3). MS (m / e): 573.3 (M+H).
[0404] Step 2: N-(3-aminopropyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide
[0405] tert-Butyl (3-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)carbamate (1.596 g, 2.79 mmol) was combined with MeOH (30 ml) to give a brown solution. Hydrochloric acid solution (4 M in dioxane) CAS[7647-01-0] (6.97 ml, 27.9 mmol) was added, and the reaction mixture was stirred at 20 °C overnight. The brown solution was neutralized with triethylamine CAS[121-44-8] (3.38 g, 4.66 ml, 33.4 mmol). The crude solution was purified by reverse-phase flash chromatography (C18 RediSep Gold, 5% to 100% acetonitrile in water (+0.1% aqueous NH4OH)). The relevant fractions were combined, frozen at -78°C, and then lyophilized overnight to remove the solvent, affording the title compound as a light brown lyophilized solid (1015 mg, 2.08 mmol, 74.8% yield). MS (m / e): 471.3 (M−H)−.
[0406] Step 3: tert-Butyl ((1s,3s)-3-((3-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)carbamoyl)cyclobutyl)carbamate
[0407] Similarly to the procedure described for Example 3, step 5, the title compound was prepared from N-(3-aminopropyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide and (1s,3s)-3-((tert-butoxycarbonyl)amino)cyclobutane-1-carboxylic acid [1008773-79-2]. MS (m / e): 668.5 (M+H). Step 4: tert-Butyl ((1s,3s)-3-((3-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)2-ethylbenzamido)propyl)carbamoyl)cyclobutyl)carbamate
[0408] Similarly to the procedure described for Example 481, Step 2, the title compound was obtained as tert-butyl ((1s,3s)-3-((3-(2-ethyl-4-((3-(3-(trifluoromethyl))-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)carbamoyl)cyclobutyl)carbamate MS (m / e): 707.6(MH)-.
[0409] Step 5: N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide formate
[0410] Similarly to the procedure described for Example 481, Step 3, the title compound was obtained as tert-butyl ((1s,3s)-3-((3-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)2-ethylbenzamido)propyl)carbamoyl)cyclobutyl)carbamate MS (m / e): 653.5 (M+HCOO)-.
[0411] The following examples were synthesized similarly to the procedures described above. The reaction sequences and starting materials are recorded in Table 2. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6]
[0412] Example 499 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide formate [ka]
[0413] Step 1: 2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]acetate
[0414] To a solution of 2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoic acid (Example 1, Step 2) (3 g, 7.35 mmol), glycine ethyl ester hydrochloride (2.05 g, 14.7 mmol), and N,N-diisopropylethylamine (5.12 mL, 29.4 mmol) in DMF (30 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (4.19 g, 11.02 mmol). The reaction was stirred at 20 °C for 16 h. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated to give the title compound as a yellow solid (4 g, 8.11 mmol, 110.33% yield). MS (m / e): 494.2 (M+H).
[0415] Step 2: 2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]acetic acid
[0416] To a solution of ethyl 2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]acetate (4 g, 8.11 mmol) in THF (30 mL) / methanol (30 mL) was added aqueous lithium hydroxide (30 mL, 30 mmol). The reaction was stirred at 20 °C for 0.33 h. The reaction mixture was adjusted to pH = 3 with 3 N HCl solution. A large amount of solid formed, which was filtered and collected. The filter cake was dried to give the title compound as an off-white solid (3.7 g, 7.95 mmol, 98.08%). MS (m / e): 466.2 (M+H).
[0417] Step 3: 4-Iodo-3-(trifluoromethyl)-1H-pyrazole
[0418] To a solution of 3-(trifluoromethyl)pyrazole (74 g, 543.8 mmol) in aqueous sulfuric acid (160 mL, 543.8 mmol) was added N-iodosuccinimide (146.81 g, 652.56 mmol) at 0 °C, and the mixture was stirred for 10 min. The mixture was heated to 20 °C and stirred for 1 h. Water (2 L) was added to the mixture, and the mixture was stirred at 20 °C for 12 h. The reaction mixture was filtered. The filter cake was dissolved in EtOAc (1.5 L) and washed with saturated NaSO (1 L). The organic layer was washed with brine (1 L), dried over NaSO, filtered, and concentrated. The residue was purified by column chromatography (SiO, PE:EtOAc = 3:1) to give the title compound as a white solid (125.6 g, 479.44 mmol, 88.17% yield). MS (m / e): 262.9 (M+H).
[0419] Step 4: 2-[4-iodo-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile
[0420] To a mixture of 4-iodo-3-(trifluoromethyl)-1H-pyrazole (30 g, 114.52 mmol) in acetone (600 mL) was added potassium carbonate (18.99 g, 137.42 mmol) and 2-bromoacetonitrile (16.48 g, 137.42 mmol) at -60 °C. The mixture was stirred at 20 °C for 4 hours. The mixture was poured into water (200 mL). The aqueous phase was extracted with EtOAc (200 mL × 2). The combined organic layers were washed with brine (300 mL), dried over NaSO, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether = 20 / 1) to give the title compound (30 g, 99.66 mmol, 87.03% yield) as a colorless oil. MS (m / e): 334.9 (M+H).
[0421] Step 5: 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile
[0422] To a solution of 2-[4-iodo-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile (10 g, 33.22 mmol) in DMF (100 mL) was added 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (4.07 g, 4.98 mmol), potassium acetate (9.78 g, 99.66 mmol), and bis(pinacolato)diboron (12.65 g, 49.83 mmol) under N2, and the reaction was then stirred at 80 °C for 16 h. The reaction mixture was poured into water (400 mL) and extracted with EtOAc (200 mL x 3). The combined organic phase was washed with brine (200 mL x 3), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography eluted with PE: EtOAc = 20: 1 to 5: 1 to give the title compound as a yellow oil (8.6 g, 28.56 mmol, yield 85.98%, purity 60%).
[0423] Step 6: 2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]acetic acid
[0424] To a solution of 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile (4.31 g, 8.6 mmol) and 2-[[2-ethyl-4-[(3-iodoimidazo[1,2-a]pyrazin-8-yl)amino]benzoyl]amino]acetic acid (2 g, 4.3 mmol) in DMSO (20 mL) was added 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (350.78 mg, 0.430 mmol) and sodium carbonate (1 g, 9.46 mmol). The reaction was stirred at 80 °C under N for 12 hours. The reaction mixture was diluted with water (50 mL) and the pH was adjusted to 4 with formic acid. EtOAc (100 mL) was added, and the mixture was stirred and filtered. The filtrate was extracted with EtOAc (50 mL). The organic layer was washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated. The residue was diluted with water (50 mL) and adjusted to pH = 10 with DIPEA. It was then extracted with EtOAc (100 mL). The aqueous layer was adjusted to pH = 4 with formic acid and filtered. The filter cake was dried to give the title compound as a brown solid (900 mg, 1.76 mmol, 40.86%). MS (m / e): 513.2 (M+H).
[0425] Step 7: tert-...
Claims
1. Formula (I) 【Chemistry 1】 (In the formula, (a) X is 【Chemistry 2】 where: (i) R 1 and R 2 together with the N atom to which they are attached, may be substituted C 1 -C 19 - forming a heterocyclic ring; or (ii) R 1 teeth, (i) hydrogen; (ii) optionally substituted C 1 -C 6 - alkyl; (iii) optionally substituted C 2 -C 6 -alkenyl; (iv) optionally substituted C 2 -C 6 -alkynyl; (v) optionally substituted C 1 -C 6 -alkoxy; (vi) optionally substituted C 1 -C 19 -heterocyclyl; and (vii) optionally substituted C 3 -C 12 -cycloalkyl; selected from the group consisting of: R 2 is hydrogen or C 1 -C 6 alkyl or (b) X is 【Transformation 3】 where: R 1a teeth, (i) optionally substituted C 1 -C 6 - alkyl; (ii) optionally substituted C 2 -C 6 -alkenyl; (iii) optionally substituted C 2 -C 6 -alkynyl; (iv) optionally substituted C 1 -C 19 -heterocyclyl; and (v) optionally substituted C 3 -C 12 -cycloalkyl; selected from the group consisting of: R 2a is C 1 -C 6 - alkyl; R 3 , R 4 , R 8 and R 9 are independently hydrogen, halogen and C 1 -C 6 - selected from the group consisting of alkyl; R 5 is halogen, cyano, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkenyl, optionally substituted C 1 -C 6 -Alkyl, C 1 -C 6 -alkyl-S- and groups 【Chemistry 4】 selected from the group consisting of: R 6 and R 7 are independently hydrogen, halogen, cyano, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkenyl, optionally substituted C 1 -C 6 -Alkyl, C 1 -C 6 -alkyl-S- and groups 【Transformation 5】 selected from the group consisting of: L 1 is a carbonyl, a covalent bond and C 1 -C 6 - selected from the group consisting of alkyldiyl; A is optionally substituted C 3 -C 12 -cycloalkyl, optionally substituted C 1 -C 19 -heterocyclyl, optionally substituted C 6 -C 14 -aryl, and optionally substituted C 1 -C 13 -heteroaryl) or a pharmaceutically acceptable salt thereof.
2. The compound of formula (I) is represented by formula (II): 【Transformation 6】 (In the formula, (i) R 1 and R 2 together with the N atom to which they are attached form a C 1 -C 19 -heterocycle, wherein said C 1 -C 19 -heterocycle is selected from the group R 17 -C 1 -C 6 -alkyl-L 4 -, amino, hydroxy and the group 【Transformation 7】 or (ii) R 1 is (i) hydrogen; (ii) C 2 -C 6 -alkenyl-NH—, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxycarbonyl-NH—, C 2 -C 6 -alkynyl-NH—, amino, cyano, hydroxy and groups 【Transformation 8】 C 1 -C 6 -alkyl optionally substituted by 1 to 2 substituents selected from the group consisting of: (iii) R 10 —C 1 -C 6 -alkyl-L 2 —C 1 -C 6 -alkyl-; (iv) C 2 -C 6 -alkynyl; (v) amino-C 1 -C 6 -alkoxy; and (vi) group 【Chemistry 9】 selected from the group consisting of: R 2 is hydrogen or C 1 -C 6 alkyl; R 10 is selected from the group consisting of amino, (C 1 -C 6 -alkyl) 2 N—, C 2 -C 6 -alkynyl, amino-C 1 -C 6 -alkyl-NH—, carbamoyl and guanidino; R 11 is hydroxy-C 1 -C 19 -heterocyclyl-C(O)-; R 12 is selected from the group consisting of amino and hydroxy-C 1 -C 19 -heterocyclyl-C(O)—NH—; R 15 is selected from the group consisting of hydrogen, amino, and hydroxy; R 16 is hydrogen or C 1 -C 6 -alkyl; R 17 is selected from the group consisting of hydrogen, amino, and C 1 -C 6 -alkyl-NH—; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen or C 1 -C 6 -alkyl; L 2 is selected from the group consisting of —C(O)—NH—, —NH—C(O)—, —NH—C(O)—NH—, —CH(NH 2 )—C(O)—NH—, —NH—, and —O—; L 3 is selected from the group consisting of a covalent bond, a carbonyl, —NH—C(O)—, and —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—CH 2 —; L 5 is selected from the group consisting of —CH 2 —C(O)—, —C(O)—CH 2 —, —CH 2 —NH—C(O)—, —NH—C(O)—CH 2 —, carbonyl, —NH—C(O)—, —C(O)—NH—, and —NH—C(O)—NH—; L 6 is a covalent bond; B is C 1 -C 19 -heterocyclyl or C 3 -C 12 -cycloalkyl; C is C 1 -C 19 -heterocyclyl or C 3 -C 12 -cycloalkyl; 2. The compound of formula (I) according to claim 1, wherein D is C 1 -C 19 -heterocyclyl or C 3 -C 12 -cycloalkyl, or a pharmaceutically acceptable salt thereof.
3. During the ceremony, (i) R 1 and R 2 together with the N atom to which they are attached, 1 -C 19 - forms a heterocycle, wherein said C 1 -C 19 -Heterocycle is R 17 -C 1 -C 6 -Alkyl-L 4 -, amino, and groups 【Chemistry 10】 or (ii) R 1 but, (i) Group 【Chemistry 11】 C substituted with one substituent selected from 1 -C 6 -alkyl; and (ii) R 10 -C 1 -C 6 -Alkyl-L 2 -C 1 -C 6 -Alkyl- selected from the group consisting of: R 2 is hydrogen; R 10 is amino; R 15 is hydrogen or amino; R 16 is hydrogen; R 17 is amino or C 1 -C 6 -alkyl-NH—; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 2 is —NH—C(O)— or —O—; L 3 is carbonyl or —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—; L 5 is carbonyl or —NH—C(O)—; B is C 1 -C 19 -heterocyclyl or C 3 -C 12 -cycloalkyl; C is C 1 -C 19 -heterocyclyl or C 3 -C 12 -cycloalkyl, 3. A compound of formula (II) according to claim 2, or a pharmaceutically acceptable salt thereof.
4. During the ceremony, (i) R 1 and R 2 together with the N atom to which they are attached, form a C selected from the group consisting of 1-piperidyl, 2,6-diazaspiro[3.3]heptan-2-yl, azetidin-1-yl, and piperazin-1-yl 1 -C 19 Form a heterocycle, wherein said C 1 -C 19 The heterocycle is R 17 -CH 2 -L 4 -, R 17 -CH(CH 3 )-L 4 -, R 17 - (CH 2 ) 3 -L 4 -, amino, and groups 【Chemistry 12】 or (ii) R 1 but, (i) Group 【Chemistry 13】 Ethyldiyl (-(CH 2 ) 2 -); (ii)R 10 -(CH 2 ) 2 -L 2 -(CH 2 ) 2 -; (iii)R 10 -C(CH 3 ) 2 -CH 2 -L 2 -(CH 2 ) 2 -; (iv) R 10 - (CH 2 ) 2 -L 2 -CH 2 - and (v)R 10 -CH(CH 3 )-CH 2 -L 2 -(CH 2 ) 2 - selected from the group consisting of: R 2 is hydrogen; R 10 is amino; R 15 is hydrogen or amino; R 16 is hydrogen; R 17 is amino or CH 3 NH—; R 18 is selected from the group consisting of hydrogen, amino, and hydroxy; R 19 is hydrogen; L 2 is —NH—C(O)— or —O—; L 3 is carbonyl or —C(O)—NH—; L 4 is selected from the group consisting of a covalent bond, a carbonyl, and —NH—C(O)—; L 5 is carbonyl or —NH—C(O)—; B is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, cyclopentyl, cyclobutyl, piperazin-1-yl, and 1-piperidyl; C is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1-piperidyl, 3-piperidyl, cyclobutyl, and cyclopentyl; 4. A compound of formula (II) according to claim 3, or a pharmaceutically acceptable salt thereof.
5. R 3 is C 1 -C 6 - alkyl or halogen; R 4 is hydrogen; R 8 is hydrogen; The compound of formula (I) according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R 9 is hydrogen or halogen.
6. R 3 is selected from the group consisting of methyl, ethyl, and chloro; R 4 is hydrogen; R 8 is hydrogen; A compound of formula (I) according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R 9 is hydrogen or fluoro.
7. R 5 But halogen, cyano, C 1 -C 6 -Alkyl-S-, halo-C 1 -C 6 - alkyl or group 【Chemistry 14】 and R 6 But hydrogen, C 1 -C 6 -Alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkenyl and groups 【Chemistry 15】 wherein C is selected from the group consisting of 1 -C 6 - alkyl is C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxycarbonyl, hydroxy, halogen, (C 1 -C 6 -alkyl) 2 N-, C 1 -C 6 -alkyl-NH-, amino, carbamoyl, carboxy, cyano and CF 3 optionally substituted with 1 to 2 substituents selected from the group consisting of: R 7 is hydrogen or C 1 -C 6 -alkyl; R 13 is selected from the group consisting of hydrogen, halogen, amino, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy and C 3 -C 12 -cycloalkyl-C 1 -C 6 -alkyl-; R 14 is selected from the group consisting of hydrogen, halogen, and C 1 -C 6 -alkyl; A compound of formula (I) according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of C 3 -C 12 -cycloalkyl, C 1 -C 19 -heterocyclyl and C 1 -C 13 -heteroaryl.
8. R 5 Halo-C 1 -C 6 - alkyl; R 6 But hydrogen, C 1 -C 6 -Alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, halo-C 2 -C 6 -alkenyl and groups 【Chemistry 16】 wherein C is selected from the group consisting of 1 -C 6 - alkyl is C 1 -C 6 -alkoxy, halogen, cyano and CF 3 optionally substituted with 1 to 2 substituents selected from the group consisting of: R 7 is hydrogen; R 13 is hydrogen; R 14 is hydrogen; L 1 is a covalent bond or —CH 2 —; A compound of formula (I) according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein A is C 3 -C 12 -cycloalkyl.
9. R 5 is CF 3 or CHF 2 and R 6 is hydrogen, methyl, ethyl, propyl, vinyl, prop-2-ynyl, halo-C 2 -C 6 -alkenyl and groups 【Chemistry 17】 wherein said methyl, said ethyl and said propyl are selected from the group consisting of methoxy, fluoro, cyano and CF 3 optionally substituted with 1 to 2 substituents selected from the group consisting of: R 7 is hydrogen; R 13 is hydrogen; R 14 is hydrogen; L 1 is a covalent bond or —CH 2 —; 7. A compound of formula (I) according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein A is cyclopropyl or cyclobutyl.
10. R 1a is amino-C 1 -C 6 2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is - alkyl.
11. The compound of formula (I) is N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (2S)—N-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide; [2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; 2-amino-1-[4-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-(pyridin-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[difluoromethyl-[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-3-[(3S)-pyrrolidin-3-yl]urea; 2-[4-[8-[4-[4-(3-aminocyclobutanecarbonyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[3-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[3-chloro-4-[4-hydroxy-4-(methylaminomethyl)piperidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-ethyl-N-methyl-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(3-aminocyclobutanecarbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-(methoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl)-4-[[3-[1-(2,2-difluoroethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(methoxymethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-propyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-cyclopentyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-propan-2-yl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-methylbutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyclopropylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-ethyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1-(3,3,3-trifluoropropyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (2S)—N-[2-[[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide; (2S)—N-[2-[[4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]ethyl]pyrrolidine-2-carboxamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide; 4-[[3-[1-[[3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-prop-2-ynylbenzamide; (2S)—N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]pyrrolidine-2-carboxamide; 2-fluoro-6-methyl-N-prop-2-ynyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-prop-2-ynylbenzamide; 2-fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methyl-N-prop-2-ynylbenzamide; 2-fluoro-6-methyl-N-prop-2-ynyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-(3-aminopropyl)-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methylbenzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [4-(aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2S)-1-aminopropan-2-yl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [4-(aminomethyl)piperidin-1-yl]-[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylphenyl]methanone; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-6-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methylbenzamide; [4-(aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[3-(prop-2-ynylamino)propyl]benzamide; [2-fluoro-6-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]benzamide; [2-fluoro-6-methyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; [4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylphenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; [2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; 2-fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methylphenyl]-piperazin-1-ylmethanone; 2-fluoro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-6-methyl-N-[3-(prop-2-ynylamino)propyl]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methylbenzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]benzamide; 2-[4-[8-[3-fluoro-5-methyl-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-amino-1-[4-[2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; [2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-(2,6-diazaspiro[3.3]heptan-2-yl)methanone; N-[2-(2-aminoethoxy)ethyl]-2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(5-aminopentyl)-2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-[(2-methyl-1,3-thiazol-4-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-aminopropan-2-yl]-2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-[(1-methylimidazol-2-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-fluoro-6-methyl-N-[3-(prop-2-ynylamino)propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-fluoro-6-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethylamino)-2-oxoethyl]-4-[[3-[1-but-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-chlorobenzamide; N-[(2R)-1-(4-aminopiperidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(2R)-1-oxo-1-piperazin-1-ylpropan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-[(3-aminocyclobutyl)amino]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(2R)-1-oxo-1-[[(3R)-pyrrolidin-3-yl]amino]propan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-[(3S)-3-aminopyrrolidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-(2-aminoethylamino)-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(2R)-1-oxo-1-[[(3S)-pyrrolidin-3-yl]amino]propan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-[(3R)-3-aminopyrrolidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(2R)-1-[2-(dimethylamino)ethylamino]-1-oxopropan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-(3-aminoazetidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-(3-aminoazetidine-1-carbonyl)-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; (3-aminoazetidin-1-yl)-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 2-[4-[8-[3-chloro-4-(2,6-diazaspiro[3.3]heptane-2-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; (4-aminopiperidin-1-yl)-[2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-chloro-4-[[3-[1-(difluoromethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-aminopropan-2-yl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2R)-1-aminopropan-2-yl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-(2,6-diazaspiro[3.3]heptan-2-yl)methanone; N,2-diethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N,2-diethylbenzamide; N,2-diethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-[(5-methyl-1H-pyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-prop-2-enylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-prop-2-ynylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; 2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 2-chloro-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[(2S)-1-(4-aminopiperidin-1-yl]-1-oxopropan-2-yl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(2S)-1-oxo-1-[[(3S)-pyrrolidin-3-yl]amino]propan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; tert-butyl N-[(2R)-2-[[2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]carbamate; tert-butyl N-[(2R)-2-[[2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]carbamate; tert-butyl N-[(2R)-2-[[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzoyl]amino]propyl]carbamate; 2-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; 2-[4-[8-[4-[4-(2-aminoacetyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-(azetidin-3-yl)-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]ethanone; [2-chloro-4-[[3-[1-[(1-methylpyrazol-4-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; [2-chloro-4-[[3-[1-(pyridazin-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-[2-(4-aminopiperidin-1-yl)-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(3-aminocyclobutyl)amino]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(2S)-1-oxo-1-piperazin-1-ylpropan-2-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(3-aminoazetidin-1-yl)-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]piperidine-4-carboxamide; (2S,4R)—N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-4-hydroxypyrrolidine-2-carboxamide; 1-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-3-[(3S)-pyrrolidin-3-yl]urea; N-[(2R)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; (2S,4R)-N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]-4-hydroxypyrrolidine-2-carboxamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperidin-4-yl]piperidine-4-carboxamide; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-[(6-methoxypyridazin-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; [2-chloro-4-[[3-[1-[(5-methylpyrimidin-2-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; [2-chloro-4-[[3-[1-[(4-methylpyrimidin-2-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-chloro-N-(2-oxo-2-piperazin-1-ylethyl)-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-[(6-methylpyridazin-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[2-[2-(dimethylamino)ethylamino]-2-oxoethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethylamino)-2-oxoethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (3-aminoazetidin-1-yl)-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 1-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-3-[(3R)-pyrrolidin-3-yl]urea; [2-chloro-4-[[3-[1-(pyrimidin-2-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]piperidine-4-carboxamide; 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-3-[(3R)-pyrrolidin-3-yl]urea; 1-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-3-[(3S)-pyrrolidin-3-yl]urea; (2S,4R)—N-[1-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-4-hydroxypyrrolidine-2-carboxamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (2S,4R)-N-[1-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]azetidin-3-yl]-4-hydroxypyrrolidine-2-carboxamide; N-[2-(2-amino-2-methylpropoxy)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-[4-[8-[4-[4-(4-aminopiperidine-1-carbonyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(3R)-aminopyrrolidine-1-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(3S)-3-aminopyrrolidine-1-carbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; [2-chloro-4-[[3-[1-[(2-methylpyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; [2-chloro-4-[[3-[1-(pyrimidin-5-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; [2-chloro-4-[[3-[1-[(1-methylpyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-ethyl-N-[3-(prop-2-ynylamino)propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[1-[(1,5-dimethylpyrazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-[4-[8-[3-chloro-4-[4-[(2R)-pyrrolidine-2-carbonyl]piperazine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2S)-2-aminopropanoyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2R)-2-aminopropanoyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[3-chloro-4-[4-[(3S)-pyrrolidine-3-carbonyl]piperazine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[3-chloro-4-[4-[(3R)-pyrrolidine-3-carbonyl]piperazine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(1S,3R)-3-aminocyclopentanecarbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[3-(2-aminoethylcarbamoylamino)propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-[4-[(1R,3S)-3-aminocyclopentanecarbonyl]piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[3-[[(2S)-2,6-diaminohexanoyl]amino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-ethyl-N-[3-(prop-2-enylamino)propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2R)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; N-(4-aminocyclohexyl)-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-[(2S,4R)-4-aminopyrrolidine-2-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-(2-aminoethoxy)-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-(4-aminopiperidine-1-carbonyl)-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[2-[(2S)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(2R)-2-aminopropoxy]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(3-ethoxypropyl)-2-ethylbenzamide; (2S)-2-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; (2R)-2-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone; 2-[4-[8-[3-chloro-4-[4-[(2S)-pyrrolidine-2-carbonyl]piperazine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[3-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]propyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[3-(3-aminopropanoylamino)propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(azetidin-3-yl)-4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-[3-(4-aminobutanoylamino)propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[[(2S)-2-amino-3-carbamimidamidopropanoyl]amino]ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(4-aminobutanoylamino)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethylcarbamoylamino)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[3-ethyl-4-[4-hydroxy-4-(methylaminomethyl)piperidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-[2-(3-aminopropanoylamino)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[[(2S)-2,6-diaminohexanoyl]amino]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethylcarbamoylamino)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-ethoxypropyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[2-[[(2S)-2,6-diaminohexanoyl]amino]ethyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-[(1R,2S)-2-aminocyclopropanecarbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 2-[4-[8-[3-chloro-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(6-aminohexyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-(2-aminoethoxy)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-(2-aminoethyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-ethylbenzamide; 2-chloro-N-(cyanomethyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-but-3-yn-2-yl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[(1S,3R)-3-aminocyclopentyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(2-hydroxyethyl)benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-[(5-methyl-1,2-oxazol-3-yl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[3-chloro-4-(3-hydroxyazetidine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(2R)-2-hydroxypropyl]benzamide; N-[(1R,3S)-3-aminocyclopentyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(2-methoxyethyl)benzamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(2S)-2-hydroxypropyl]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(oxetan-3-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[3-chloro-4-(3-hydroxy-3-methylazetidine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[3-chloro-4-[(3S)-3-hydroxypyrrolidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[3-chloro-4-[(3R)-3-hydroxypyrrolidine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; [4-[(2R,4S)-4-aminopyrrolidine-2-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-(azetidin-3-yl)-4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S)-3-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R)-3-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(cyanomethyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzamide; N-(4-aminocyclohexyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; 3-[4-[8-[4-[4-(3-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]propanenitrile; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide; 2-[4-[8-[3-ethyl-4-(piperazine-1-carbonyl)anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 4-[2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzamide; N-[2-(1-aminocyclopropyl)ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-(3-aminocyclobutyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; [4-(3-aminoazetidine-1-carbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxy-2-methylpropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-hydroxybutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-pyrrolidin-1-ylethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-[2-(2-aminoethoxy)ethylcarbamoyl]-3-ethylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetic acid; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-prop-2-enyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-cyclobutyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-chloroprop-2-enyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(3-chlorobut-3-en-2-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[(2,2-difluorocyclopropyl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(1-chloro-3-hydroxypropan-2-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[2-(chloromethyl)-3-hydroxy-2-methylpropyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N,2-diethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-methyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-ethyl-N-methyl-4-[[3-[1-(pyrimidin-4-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(2-aminoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; 2-chloro-N-methyl-4-[[3-[1-(1H-pyrazol-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(4-aminopiperidine-1-carbonyl)piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 2-[4-[8-[4-[4-(3-aminopropanoyl)piperazine-1-carbonyl]-3-chloroanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(4-aminocyclohexyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide; N-(3-aminocyclobutyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-[(1S,3S)-3-aminocyclopentyl]-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide; 3-amino-1-[4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; [4-[(2S,4S)-4-aminopyrrolidine-2-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 4-[2-chloro-4-[[3-[1-(2-methoxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide; 4-[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide; 2-ethyl-N-methyl-4-[[3-[1-[2-(methylamino)ethyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(3-aminopropanoylamino)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(4-aminobutanoylamino)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-fluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyclobutylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[(3,3-difluorocyclobutyl)methyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-hydroxyethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(oxolan-3-ylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(3R)-1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-[2-(dimethylamino)ethyl]-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; Ethyl 2-[4-[8-[4-[2-(2-aminoethoxy)ethylcarbamoyl]-3-ethylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetate; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxy-3-methylbutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(3-hydroxypropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(3S)-1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,3-dihydroxypropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2,4-dihydroxybutyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-ethyl-4-[[3-[1-(2-morpholin-4-ylethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (4-aminopiperidin-1-yl)-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-(5-aminopentyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [(3S)-3-aminopyrrolidin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[(3S)-3-methylpiperazin-1-yl]methanone; N-(2-aminoethyl)-2-chloro-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[(3R)-3-methylpiperazin-1-yl]methanone; [(3R)-3-aminopyrrolidin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[(2S)-2-methylpiperazin-1-yl]methanone; [4-[(3R)-3-aminopyrrolidine-1-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3S)-3-aminopyrrolidine-1-carbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; N-(5-aminopentyl)-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; (2S)-2-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone; (2R)-2-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; 2-ethyl-N-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(6-aminohexyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; N-[3-(3-aminopropanoylamino)propyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; [4-[(1R,3S)-3-aminocyclopentanecarbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; [4-[(1S,3R)-3-aminocyclopentanecarbonyl]piperazin-1-yl]-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; 4-[[3-[1-(3-cyanopropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-methylbenzamide; N-[3-(4-aminobutanoylamino)propyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[3-[[(2S)-2,6-diaminohexanoyl]amino]propyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-propylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1-methylpyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; 4-[[3-[1-(azetidin-3-yl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-chloro-N-methylbenzamide; N-[(2S)-1-aminopropan-2-yl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-ethyl-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-methyl-4-[[3-[1-prop-2-ynyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(3-hydroxypiperidine-3-carbonyl)piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,5R)-5-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; [2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; [2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]methanone; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 4-[[3-[1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-chloro-N-methylbenzamide; 2-chloro-4-[[3-[1-(2-cyanoethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; 2-chloro-4-[[3-[1-(3-cyanopropyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-methylbenzamide; N-[2-(2-aminoethoxy)ethyl]-2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(2-aminoethoxy)ethyl]-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(4-aminobutyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(2-aminoethyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(3-aminopropyl)-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[3-chloro-4-[4-(piperidine-4-carbonyl)piperazine-1-carbonyl]anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; (2S,4R)-N-[3-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]2-methylbenzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4R)-N-[3-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]cyclobutyl]-4-hydroxypyrrolidine-2-carboxamide; 2-chloro-N-[1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]azetidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; [4-(aminomethyl)piperidin-1-yl]-[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; rac-(2R,4S)-N-[3-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]cyclopentyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4R)-N-[4-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]cyclohexyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4R)-N-[2-[[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide; 4-[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]-N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide; 2-chloro-N-[(3S)-pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[(3R)-pyrrolidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-[4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-chloro-N-[1-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperidin-4-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-[4-[8-[4-[4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(3-aminocyclobutyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(4-aminocyclohexyl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[1-[rac-(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperidin-3-yl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide; N-(3-aminopropyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide; N-(2-aminoethyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-(azetidin-3-ylmethyl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-(azetidin-3-yl)-4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 4-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]butan-1-one; 3-amino-1-[4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(piperidine-4-carbonyl)piperazin-1-yl]methanone; 2-chloro-N,N-dimethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(azetidin-3-yl)-2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-[rac-(1R,3R)-3-aminocyclopentyl]-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(azetidin-3-yl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-(azetidin-3-ylmethyl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 2-chloro-N-piperidin-4-yl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-chloro-N-piperidin-3-yl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S)-pyrrolidin-3-yl]piperazine-1-carboxamide; 4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R)-pyrrolidin-3-yl]piperazine-1-carboxamide; N-(3-aminopropyl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; 3-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]propan-1-one; 4-[4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methylbenzoyl]-N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide; 4-amino-1-[4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazin-1-yl]butan-1-one; 2-[4-[8-[4-[4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-(4-hydroxypiperidine-4-carbonyl)piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; 2-[4-[8-[4-[4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazine-1-carbonyl]-3-methylanilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(2-aminoethyl)-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; (2S,4R)-N-[3-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-(difluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethylbenzamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; (2S,4R)-N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4R)-N-[2-[[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4R)-N-[3-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4S)-4-ethyl-N-[2-[[2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide; [4-(3-hydroxypiperidine-3-carbonyl)piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; (2S,4R)-N-[3-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxamide; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,5R)-5-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide; 4-[2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]-N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]piperazine-1-carboxamide; (2S,4R)-4-hydroxy-N-[3-[[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]pyrrolidine-2-carboxamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazin-1-yl]methanone; (2S,4R)-4-hydroxy-N-[2-[[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]pyrrolidine-2-carboxamide; (2S,4R)-N-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4S)-4-ethyl-N-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxypyrrolidine-2-carboxamide; (2S,4S)-N-[2-[[2-ethyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]-4-hydroxy-4-methylpyrrolidine-2-carboxamide; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone; [2-chloro-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]methanone; (2S,4R)-4-hydroxy-N-[3-[[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]propyl]pyrrolidine-2-carboxamide; (2S,4R)-4-hydroxy-N-[2-[[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]ethyl]pyrrolidine-2-carboxamide; N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; [4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,4R)-4-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-[4-[rac-(3R,4S)-4-hydroxypiperidine-3-carbonyl]piperazin-1-yl]methanone; N-[(3R,4R)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; N-[(3S,4S)-4-hydroxypyrrolidin-3-yl]-4-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]piperazine-1-carboxamide; [4-(4-hydroxypiperidine-4-carbonyl)piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(2S,4S)-4-hydroxy-4-methylpyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(2S,4R)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3R,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3S,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(2R,4S)-4-hydroxypyrrolidine-2-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3S,4R)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [4-[(3R,4S)-3-hydroxypiperidine-4-carbonyl]piperazin-1-yl]-[2-methyl-4-[[3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]methanone; [2-methyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]-piperazin-1-ylmethanone; 2-(4-(8-((4-(4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(3-((1R,3S)-3-(12-azanayl)cyclopentane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)piperidine-4-carboxamide; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (S)-3-amino-N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)pyrrolidine-1-carboxamide; N-(2-((1R,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (S)—N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1R,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1R,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; cis-N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-(2,6-diazaspiro[3.3]heptan-2-yl)-2-oxo-ethyl]-2-ethyl-benzamide; N-[2-(3-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-(3-methylpiperazin-1-yl)-2-oxo-ethyl]benzamide; N-[2-(6-amino-2-azaspiro[3.3]heptan-2-yl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-[3-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-[2-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-(3-azabicyclo[3.1.0]hexan-6-ylamino)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-oxo-ethyl]-2-ethyl-benzamide; N-(azetidin-3-ylmethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; 2-ethyl-N-(2-azaspiro[3.3]heptan-6-yl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(azetidin-3-yl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone; (R)-3-amino-N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)pyrrolidine-1-carboxamide; ((3-aminopropyl)imino)(methyl)(2-methyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)-16-sulfanone; (4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone; (R)-3-amino-N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)pyrrolidine-1-carboxamide; N-[2-(azetidin-3-ylmethylamino)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-2-ylmethylamino)ethyl]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-3-ylmethylamino)ethyl]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(4-piperidylmethylamino)ethyl]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-[(4-hydroxy-4-piperidyl)methylamino]-2-oxo-ethyl]benzamide; N-[2-(2,6-diazaspiro[3.3]heptan-2-yl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-[3-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-[2-(aminomethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-(3-azabicyclo[3.1.0]hexan-6-ylamino)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-(azetidin-2-ylmethylamino)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(3-((1r,3r)-3-aminocyclobutane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(3-((1R,3S)-3-aminocyclopentane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(3-((1S,3R)-3-aminocyclopentane-1-carboxamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(2-(3-aminopropanamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(4-aminobutanamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-[2-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-((1s,3s)-3-aminocyclobutyl)-4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(4-aminobutanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(3-((1s,3s)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(3-((1r,3r)-3-aminocyclobutane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(3-((1R,3S)-3-aminocyclopentane-1-carboxamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-[2-(3-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-(3-methylpiperazin-1-yl)-2-oxo-ethyl]benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-[(3-hydroxyazetidin-3-yl)methylamino]-2-oxo-ethyl]benzamide; N-[2-(azetidin-3-ylmethylamino)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-2-ylmethylamino)ethyl]benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(pyrrolidin-3-ylmethylamino)ethyl]benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-(4-piperidylmethylamino)ethyl]benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-[(4-hydroxy-4-piperidyl)methylamino]-2-oxo-ethyl]benzamide; (2S,4R)—N-((1s,3R)-3-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)cyclobutyl)-4-hydroxypyrrolidine-2-carboxamide; N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)piperidine-4-carboxamide; N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)piperidine-4-carboxamide; (4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)(2,6-diazaspiro[3.4]octan-6-yl)methanone; (3-aminoazetidin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone; N-(azetidin-3-ylmethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(3-amino-2-(chloromethyl)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)(1,6-diazaspiro[3.3]heptan-1-yl)methanone; (2-(aminomethyl)-2-(chloromethyl)azetidin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone; (2,5-diazabicyclo[2.2.1]heptan-2-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone; N-(3-azabicyclo[3.1.0]hexan-6-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(piperidin-3-yl)benzamide; (4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)(1,6-diazaspiro[3.3]heptan-6-yl)methanone; N-(azetidin-3-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(3-aminopropanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1r,3r)-3-aminocyclobutane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; 4-amino-N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)piperidine-1-carboxamide; N-(2-(3-(3-aminopropyl)ureido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; 1-(4-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-2-(piperidin-4-yl)ethan-1-one; (4-(2-aminoethyl)piperazin-1-yl)(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone; 2-(4-(8-((3-chloro-4-(4-(2-(piperidin-4-yl)acetyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; 2-(4-(8-((4-(4-((1R,3R)-3-aminocyclopentane-1-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (4-((1R,3R)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone; (4-((1S,3S)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone; (S)-3-amino-N-(2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)ethyl)pyrrolidine-1-carboxamide; (S)-3-amino-N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)pyrrolidine-1-carboxamide; 1-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-2-(piperidin-4-yl)ethan-1-one; 4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-N-((3-hydroxyazetidin-3-yl)methyl)piperazine-1-carboxamide; 4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-N-((3-hydroxyazetidin-3-yl)methyl)piperazine-1-carboxamide; N-(azetidin-3-yl)-4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carboxamide; 2-(4-(8-((4-(4-((1S,3S)-3-aminocyclopentane-1-carbonyl)piperazine-1-carbonyl)-3-chlorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (4-((1S,3S)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)methanone; N-((1s,3s)-3-aminocyclobutyl)-4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carboxamide; N-((1s,3s)-3-aminocyclobutyl)-4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazine-1-carboxamide; N-[2-[[(1R,3R)-3-aminocyclopentanecarbonyl]amino]ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-(2-((1R,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-((1S,3S)-3-aminocyclopentane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; 4-((3-(1-((1-(cyanomethyl)-1H-pyrazol-3-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-methylbenzamide; 2-chloro-4-((3-(1-((1-(cyanomethyl)-1H-pyrazol-3-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-methylbenzamide; 2-chloro-4-((3-(1-(2-(dimethylamino)ethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-methylbenzamide; 4-((3-(1-(1-benzylpiperidin-4-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide; 4-((3-(1-((1-benzylpyrrolidin-3-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide; 4-((3-(1-(3-(4-(aminomethyl)phenyl)propyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide; 4-((3-(1-(3-(2-aminoethyl)benzyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-chloro-N-methylbenzamide; N-[4-[N-(3-aminopropyl)-S-methyl-sulfonimidoyl]-3-methyl-phenyl]-3-[1-(cyclopropylmethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-amine; 2-[4-[8-[4-[N-(3-aminopropyl)-S-methyl-sulfonimidoyl]-3-methyl-anilino]imidazo[1,2-a]pyrazin-3-yl]-3-(trifluoromethyl)pyrazol-1-yl]acetonitrile; N-(2-aminoethyl)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamide; N-(azetidin-3-yl)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamide; (S)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-N-(pyrrolidin-3-yl)acetamide; (R)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-N-(pyrrolidin-3-yl)acetamide; N-(2-aminoethyl)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamide; N-(3-aminopropyl)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamide; N-(azetidin-3-yl)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamide; (S)-2-(4-(2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-N-(pyrrolidin-3-yl)acetamide; N-(3-aminopropyl)-2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)acetamide; 2-(4-(8-((3-chloro-4-(4-(2-oxo-2-(piperazin-1-yl)ethyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; 2-(4-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)-1-(piperazin-1-yl)ethan-1-one; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(3-aminopropoxy)ethyl)-2-ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(2-(2-aminoacetamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(3-aminopropoxy)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(2-(2-aminoethoxy)ethyl)-2-ethyl-4-((3-(1-(3-methylbut-2-en-1-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(6-aminohexyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; (S)—N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 2-ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)benzamide; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-pyrrolidin-1-yl)ethoxy)ethyl)benzamide; N-(2-(2-aminoacetamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)benzamide; N-(2-(2-aminoethoxy)ethyl)-2-ethyl-4-((3-(1-(2-(trifluoromethoxy)ethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-((2-aminocyclopropyl)methyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; cis-N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (R)—N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (R)—N-(3-(2-aminopropanamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (S)—N-(3-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; (S)—N-(3-(2-aminopropanamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (4-(4-((3-(1-allyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)((2R,5S)-5-hydroxypyrrolidin-2-yl)methanone; N-(3-(3-aminopropanamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (R)-3-amino-N-(3-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)pyrrolidine-1-carboxamide; (R)-3-amino-N-(3-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-1-carboxamide; (R)—N-(3-(2-aminopropanamido)propyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (S)—N-(3-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)pyrrolidine-2-carboxamide; (S)-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(6-prolyl-2,6-diazaspiro[3.3]heptan-2-yl)methanone; (S)-2-(4-(8-((3-chloro-4-(6-prolyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (2S,4R)—N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)-4-hydroxypyrrolidine-2-carboxamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-((2-aminocyclopropyl)methyl)-2-ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-((2-aminocyclopropyl)methyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-[2-[(3-aminocyclobutyl)amino]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (R)—N-(2-(2-aminopropanamido)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-(2-(2-aminoethoxy)ethyl)-2-ethyl-4-((3-(1-(3,3,3-trifluoro-2-hydroxypropyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; 4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-pyrrolidin-1-yl)ethoxy)ethyl)benzamide; (4-(2-fluoro-6-methyl-4-((3-(1-(prop-2-yn-1-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)piperazin-1-yl)((2R,5S)-5-hydroxypyrrolidin-2-yl)methanone; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(1R)-1-methyl-2-oxo-2-piperazin-1-yl-ethyl]benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide; (S)—N—((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; 2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)ethan-1-one; 2-amino-1-(6-(2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-2,6-diazaspiro[3.3]heptan-2-yl)ethan-1-one; (S)—N-(3-(2-aminopropanamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (1R,5S,6r)-N-((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-3-azabicyclo[3.1.0]hexane-6-carboxamide; (S)—N—((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(3-chloro-3-methylbutyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 2-amino-1-(6-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzoyl)-2,6-diazaspiro[3.3]heptan-2-yl)ethan-1-one; 2-(4-(8-((3-chloro-4-(6-glycyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-[2-[(3-aminocyclobutyl)amino]-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)benzamide; (R)—N-(1-aminopropan-2-yl)-2-fluoro-6-methyl-4-((3-(1-(prop-2-yn-1-yl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (S)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)propan-1-one; N-[(1R)-2-[(3S)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (2S,4R)—N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)ethyl)-4-hydroxypyrrolidine-2-carboxamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-[2-(dimethylamino)ethylamino]-2-oxo-ethyl]-2-ethyl-benzamide; N-((R)-1-((1s,3S)-3-aminocyclobutane-1-carboxamido)propan-2-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; N-(2-(3-aminopropoxy)ethyl)-4-((3-(1-(3,3-difluorocyclobutyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; N-((2-aminocyclopropyl)methyl)-4-((3-(1-cyclobutyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 2-ethyl-N-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)—N-(1-(2-aminoacetamido)propan-2-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; N-[(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; N-[2-[(3-aminocyclobutyl)amino]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 2-(4-(8-((4-(4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazine-1-carbonyl)-3-fluoro-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (R)—N-(3-(2-aminopropanamido)propyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[(1R)-1-methyl-2-oxo-2-piperazin-1-yl-ethyl]benzamide; 4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide; (R)-4-((3-(1-allyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(1-aminopropan-2-yl)-2-fluoro-6-methylbenzamide; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 2-(4-(8-((4-(4-(L-alanyl)piperazine-1-carbonyl)-3-fluoro-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-[(1R)-2-[(3-aminocyclobutyl)amino]-1-methyl-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (2S,4R)—N—((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; (R)-3-amino-N-(3-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-1-carboxamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; N-[2-[(3R)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (S)-(2-chloro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(6-prolyl-2,6-diazaspiro[3.3]heptan-2-yl)methanone; (R)—N-(1-(2-aminoacetamido)propan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; N-[(1R)-2-(4-amino-1-piperidyl)-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; N-(2-(2-aminoacetamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (4-((1R,5S,6r)-3-azabicyclo[3.1.0]hexane-6-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylphenyl)methanone; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-[2-(dimethylamino)ethylamino]-2-oxo-ethyl]benzamide; (S)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; 2-(4-(8-((3-fluoro-4-(4-glycylpiperazine-1-carbonyl)-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (R)—N-(2-(2-aminopropanamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[(1R)-2-(4-amino-1-piperidyl)-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone; 2-(4-(8-((4-(4-((1s,3s)-3-aminocyclobutane-1-carbonyl)piperazine-1-carbonyl)-3-fluoro-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-((2-aminocyclopropyl)methyl)-4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (4-((1s,3s)-3-aminocyclobutane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylphenyl)methanone; N-(3-(3-aminopropanamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 2-(4-(8-((3-fluoro-5-methyl-4-(4-(piperidine-4-carbonyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (R)—N-(1-aminopropan-2-yl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; (R)—N-(2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)piperidine-4-carboxamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-(2-oxo-2-piperazin-1-yl-ethyl)benzamide; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone; 2-ethyl-N-(3-(2-(2,2,2-trifluoroacetamido)acetamido)propyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-((R)-1-((1s,3S)-3-aminocyclobutane-1-carboxamido)propan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[(1R)-1-methyl-2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (2S,4R)—N—((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (4-(2-fluoro-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-6-methylbenzoyl)piperazin-1-yl)((2R,5S)-5-hydroxypyrrolidin-2-yl)methanone; 2-(4-(8-((3-fluoro-4-(4-((2R,5S)-5-hydroxypyrrolidine-2-carbonyl)piperazine-1-carbonyl)-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)benzamide; (S)—N-(2-(2-aminopropanamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)—N-(1-aminopropan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; (1R,5S,6r)-N-((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-3-azabicyclo[3.1.0]hexane-6-carboxamide; 2-(4-(8-((3-fluoro-4-(4-((2S,4R)-4-hydroxypyrrolidine-2-carbonyl)piperazine-1-carbonyl)-5-methylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; N-((R)-1-((S)-2-aminopropanamido)propan-2-yl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamide; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-(2-((1S,3R)-3-aminocyclopentane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[(1R)-2-[(3-aminocyclobutyl)amino]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[(1R)-1-methyl-2-oxo-2-piperazin-1-yl-ethyl]benzamide; (2S,4R)—N-(3-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; N-[2-(2-aminoethylamino)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone; 2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-[(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (4-((1r,3r)-3-aminocyclobutane-1-carbonyl)piperazin-1-yl)(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone; (R)—N-(1-aminopropan-2-yl)-2-fluoro-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-6-methylbenzamide; N-[(1R)-2-[(3S)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 2-ethyl-4-((3-(1-(2-fluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-(2-morpholinoethoxy)ethyl)benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[(1R)-1-methyl-2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-[2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; N-(2-((1s,3s)-3-aminocyclobutane-1-carboxamido)ethyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)—N-(2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)piperidine-4-carboxamide; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone; (4-((1r,3r)-3-aminocyclobutane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)methanone; (2S,4R)—N—((R)-2-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; 4-((3-(1-(1-cyanoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[(1R)-1-methyl-2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (R)-2-ethyl-N-(3-(2-(2,2,2-trifluoroacetamido)propanamido)propyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[2-[(3-aminocyclobutyl)amino]-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-[2-(3-aminoazetidin-1-yl)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-N-[2-[2-(dimethylamino)ethylamino]-2-oxo-ethyl]-2-methyl-benzamide; 2-ethyl-N-(2-oxo-2-piperazin-1-yl-ethyl)-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; (2S,4R)—N-(3-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; (4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypiperidin-4-yl)methanone; N-[2-(4-amino-1-piperidyl)-2-oxo-ethyl]-2-ethyl-4-[[3-[3-(trifluoromethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide; (S)-2-ethyl-N-(3-(2-(2,2,2-trifluoroacetamido)propanamido)propyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-[2-(2-aminoethylamino)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; N-[(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-benzamide; (S)—N—((R)-2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)pyrrolidine-2-carboxamide; (S)-(2-chloro-4-((3-(1-(difluoromethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(6-prolyl-2,6-diazaspiro[3.3]heptan-2-yl)methanone; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypiperidin-4-yl)methanone; N-[2-(2-aminoethylamino)-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; 2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; (S)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (R)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)-3-methylbutan-1-one; (2S,4R)—N—((R)-2-(4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluoro-6-methylbenzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; (4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(piperidin-4-yl)methanone; 2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; 2-ethyl-N-(2-(2-morpholinoethoxy)ethyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)-3-methylbutan-1-one; (4-(4-((3-(1-allyl-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone; (S)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; N-((2-aminocyclopropyl)methyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (R)-2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; (S)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-methyl-N-[2-oxo-2-[[(3S)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-phenyl-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (2S,4R)—N—((R)-2-(2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamido)propyl)-4-hydroxypyrrolidine-2-carboxamide; 2-fluoro-6-methyl-N-(4-(prop-2-yn-1-ylamino)butyl)-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (2R)-2-amino-1-(4-(4-((3-(1-(but-3-yn-2-yl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one (mixture of epimers); (4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone; (4-(4-((3-(1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone; (4-(4-((3-(1-(but-3-yn-2-yl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)((2R,4S)-4-hydroxypyrrolidin-2-yl)methanone (mixture of epimers); 2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; (S)—N-(3-(4-((3-(1-(2-amino-2-oxoethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)pyrrolidine-2-carboxamide; N-[(1R)-2-[(3-aminocyclobutyl)amino]-1-methyl-2-oxo-ethyl]-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypiperidin-4-yl)methanone; 2-(3-(difluoromethyl)-4-(8-((3-ethyl-4-(4-(piperidine-4-carbonyl)piperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-1H-pyrazol-1-yl)acetonitrile; 2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(prop-2-yn-1-yl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)ethan-1-one; (S)—N-(3-(2-aminopropanamido)propyl]-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; (4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone; (R)-2-amino-1-(4-(4-((3-(3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)propan-1-one; 2-(4-(8-((4-(4-(D-valyl)piperazine-1-carbonyl)-3-ethylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(difluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (4-(4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)(4-hydroxypyrrolidin-2-yl)methanone; (2R)-2-amino-1-(4-(4-((3-(1-(but-3-yn-2-yl)-3-(difluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzoyl)piperazin-1-yl)-3-methylbutan-1-one (mixture of epimers); 2-(4-(8-((4-(4-((1r,3r)-3-aminocyclobutane-1-carbonyl)piperazine-1-carbonyl)-3-ethylphenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(difluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (4-((3-(3-(difluoromethyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylphenyl)(piperazin-1-yl)methanone; N-(3-(2-aminoacetamido)propyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-N-[(1R)-1-methyl-2-oxo-2-[[(3R)-pyrrolidin-3-yl]amino]ethyl]benzamide; N-[3-[(3-aminocyclobutanecarbonyl)amino]propyl]-4-[[3-[1-(3-aminocyclobutanecarbonyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; (2-fluoro-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)(piperazin-1-yl)methanone; (4-((1S,3R)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorophenyl)methanone; 2-(4-(8-((4-(4-((1S,3R)-3-aminocyclopentane-1-carbonyl)piperazine-1-carbonyl)-3-fluorophenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; (4-((1S,3R)-3-aminocyclopentane-1-carbonyl)piperazin-1-yl)(4-((3-(1-(cyclopropylmethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorophenyl)methanone; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzamide; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzamide; N-(2-(2-aminoethoxy)ethyl)-4-((3-(1-(cyclopropylmethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzamide; 2-amino-1-(4-(4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzoyl)piperazin-1-yl)ethan-1-one; 2-(4-(8-((3-fluoro-4-(4-glycylpiperazine-1-carbonyl)phenyl)amino)imidazo[1,2-a]pyrazin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetonitrile; 2-amino-1-(4-(4-((3-(1-(cyclopropylmethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-fluorobenzoyl)piperazin-1-yl)ethan-1-one; N-(2-((2-((2-aminoethyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(2-((2-(azetidin-3-ylamino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (S)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)benzamide; (R)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)benzamide; N-(2-((2-((3-aminopropyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(2-((2-((2-aminoethyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-(2-((2-(azetidin-3-ylamino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (S)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)amino)ethyl)benzamide; (R)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-N-(2-((2-oxo-2-(pyrrolidin-3-ylamino)ethyl)amino)ethyl)benzamide; N-(2-((2-((3-aminopropyl)amino)-2-oxoethyl)amino)ethyl)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; (1S,5R)-6-[[2-chloro-4-[[3-[1-(cyanomethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]benzoyl]amino]-N!-[(3R,4R)-4-hydroxypyrrolidin-3-yl]-3-azabicyclo[3.1.0]hexane-3-carboxamide; N-(6-aminohexyl)-2-chloro-4-((3-(1-(2,2-difluoroethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-((1-(azetidin-3-ylmethyl)pyrrolidin-3-yl)methyl)-2-ethyl-4-((3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)benzamide; N-((1-(azetidin-3-ylmethyl)piperidin-4-yl)methyl)-4-((3-(1-(cyanomethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamide; 2-[Azetidin-3-ylmethyl-[5-[[4-[[3-[1-(2,2-difluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzoyl]amino]pentyl]amino]acetic acid; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-cyano-1-(cyanomethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-cyano-1-(2,2-difluoroethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; N-[2-(2-aminoethoxy)ethyl]-4-[[3-[1-(cyanomethyl)-3-methylsulfanyl-pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide; and 2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, selected from N-[2-(2-aminoethoxy)ethyl]-4-[[3-[3-chloro-1-(cyanomethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]amino]-2-ethyl-benzamide.
12. A method for preparing a compound of formula (I) according to any one of claims 1 to 11, comprising: (i) Carboxylic acid IXa [wherein R 3 ~R 9 is as defined in any one of claims 1 to 11. [Chemistry 18] of, Amine V [wherein R 1 and R 2 is as defined in any one of claims 1 to 11. 【Chemistry 19】 and react with forming a compound of formula (I) as defined above; or (ii) Compound VIa [wherein R 1 ~R 4 , R 8 and R 9 is as defined in any one of claims 1 to 11, and Z is halogen or triflate. 【Chemistry 20】 of, Compound VIIa [wherein R 5 ~R 7 is as defined in any one of claims 1 to 11, and Y is a boronic acid or a boronic ester. 【Chemistry 21】 and react with forming a compound of formula (I) A method comprising:
13. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.
15. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, for use as an antibiotic.
16. 12. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of nosocomial infections and the resulting diseases.
17. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of infections caused by Gram-negative bacteria and the resulting diseases.
18. 18. The pharmaceutical composition of claim 17, wherein the Gram-negative bacteria is selected from Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli.
19. 19. The pharmaceutical composition of claim 18, wherein the Gram-negative bacterium is Acinetobacter baumannii.
20. 12. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 11, 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 or Escherichia coli, or combinations thereof.
21. A method 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, or a combination thereof, in a non-human mammal, the method comprising administering to the non-human mammal a compound of formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof.
22. 12. Use of a compound of formula (I) according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament useful for the treatment or prevention of infections and diseases resulting therefrom caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species or Escherichia coli, or a combination thereof.
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