Rifabutin analogues for the treatment of diseases

Abstract

The present invention relates to compounds and pharmaceutical compositions comprising the same for the treatment, amelioration and / or prevention of disease. In some embodiments, the disease is a bacterial infection. In some embodiments, the bacterial infection is caused by one or more bacteria belonging to the nontuberculous mycobacteria genus, preferably M. abscessus. [Formula 1] JPEG2025513019000051.jpg9584

Description

[Technical field]

[0001] The present invention relates to compounds and pharmaceutical compositions comprising same for the treatment, amelioration and / or prevention of disease. In some embodiments, the disease is a bacterial infection. In some embodiments, the bacteria is selected from the group consisting of Clostridium spp., Enterococcus spp., Hemophilus spp., Legionella spp., Mycobacterium spp., Neisseria spp., Staphylococcus spp., Streptococcus spp., Listeria monocytogenes, Moraxella catarrhalis, Bacillus spp., Bacteroides spp., Gardnerella vaginalis, Lactobacillus spp., Mobiluncus spp., Helicobacter pylori, and / or other strains of the bacteria. pylori, Campylobacter jejuni, Chlamydia trachomatis and / or Toxoplasma gondii. In some embodiments, the infection is caused by A. baumannii, and / or S. aureus, and / or a nontuberculous mycobacterium (NTM), preferably M. abscessus. [Background technology]

[0002] Rifamycins, such as rifabutin, are effective against Clostridium spp., Enterococcus spp., Hemophilus spp., Legionella spp., Mycobacterium spp. (tuberculous and nontuberculous mycobacteria), Neisseria spp., Staphylococcus spp., Streptococcus spp., Listeria monocytogenes, Moraxella catarrhalis, Bacillus spp., Bacteroides spp., Gardnerella vaginalis, and other pathogenic bacteria. It is known as an antibiotic with activity against a broad spectrum of pathogens, such as Lactobacillus species, Mobiluncus species, Helicobacter pylori, Campylobacter jejuni, Chlamydia trachomatis, and Toxoplasma gondii (Kunin, Clin. Infect. Dis., 1996, 22(suppl 1):S3-14; Farr and Mandell, Med. Clin. North. Am., 1982; Thornsberry et al., Rev. Infect. Dis., 1983; Hoover et al., Diagn. Microbiol. Infect. Dis., 1993; Kerry et al., Diagn. Microbiol. Infect. Dis., 1994 ... al., J. Antimicrob. Chemother., 1975).

[0003] Rifabutin has recently been shown to have potent in vitro and in vivo activity against Mycobacterium abscessus (Aziz et al., Antimicrob. Agents Chemother., 2017; Dick et al., Antimicrob. Agents Chemother., 2020) and Acinetobacter baumannii (Luna et al., Nat. Microbiol., 2020; Trebosc et al., Drug Discov. Today, 2021, 26(9):2099-2014; Trebosc et al., J. Antimicrob. Chemother., 2020).

[0004] Derivatives of rifabutin have also demonstrated activity against M. avium and M. tuberculosis (WO 2004 / 005298).

[0005] However, there remains a need for more effective rifamycins for the treatment of bacterial infections such as M. abscessus and A. baumannii infections. Summary of the Invention

[0006] In one aspect, the present invention provides a compound of formula I, or a pharma- ceutically acceptable salt, tautomer, solvate, hydrate, or enantiomer thereof: [ka] During the ceremony, R A and R B are each independently -H, -C1-C6 alkyl, or C3-C6 cycloalkyl; Y is -NR 1 R 2 or [NR 51 R 52 R53 ] + X - and; R 1 and R 2 are each independently -H, -C1-C6 alkyl, -R 3 , or -C1-C6-alkylene-R 3 wherein said alkyl and said alkylene are each independently optionally substituted with one or more halogens. R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C6 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C6 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C6 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 3- to 15-membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C6 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C6 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each of -C1-C6 alkyl and -C6-C 10 Aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl; R 51 , R 52 and R 53 are each independently -C1-C6 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C6 alkyl, -OC1-C6 alkyl or -N(C1-C6 alkyl)2; and X - is independently a pharma- ceutically acceptable anion, preferably X - F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0007] In one aspect, the present invention provides a pharmaceutical composition comprising a compound of formula I as described herein or a pharma- ceutically acceptable salt thereof and a pharma- ceutically acceptable carrier. In some preferred embodiments, the pharmaceutical composition is effective for treating a bacterial infection. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the genera Acinetobacter, Staphylococcus, and / or Mycobacteria. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the species A. baumannii, and / or S. aureus, and / or nontuberculous mycobacteria, preferably M. abscessus. In a preferred embodiment, the bacterial infection is caused by one or more bacteria belonging to the nontuberculous mycobacteria, preferably M. abscessus. In some embodiments, the infection is caused by one or more bacteria belonging to the genus Acinetobacter and / or Staphylococcus, preferably A. baumannii and / or S. aureus.

[0008] In one aspect, the present invention provides a compound of formula I as described herein or a pharma- ceutically acceptable salt thereof for use as a medicament. In another aspect, the present invention provides a compound of formula I as described herein or a pharma- ceutically acceptable salt thereof for use in the prophylaxis or treatment of a bacterial infection. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the genera Acinetobacter, Staphylococcus and / or Mycobacteria. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the species A. baumannii, and / or S. aureus, and / or nontuberculous mycobacteria, preferably M. abscessus. In a preferred embodiment, the bacterial infection is caused by one or more bacteria belonging to the nontuberculous mycobacteria, preferably M. abscessus. In some embodiments, the infection is caused by one or more bacteria belonging to the genus Acinetobacter and / or Staphylococcus, preferably A. baumannii and / or S. aureus.

[0009] In one aspect, the present invention provides the use of a compound of formula I or a pharmaceutical composition comprising a compound of formula I as described herein in the manufacture of a medicament for treating a bacterial infection. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the genera Acinetobacter, Staphylococcus and / or Mycobacteria. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the species A. baumannii and / or S. aureus and / or nontuberculous mycobacteria, preferably M. abscessus. In a preferred embodiment, the bacterial infection is caused by one or more bacteria belonging to the nontuberculous mycobacteria, preferably M. abscessus. In some embodiments, the infection is caused by one or more bacteria belonging to the genus Acinetobacter and / or Staphylococcus, preferably A. baumannii and / or S. aureus.

[0010] In one aspect, the present invention provides a method of treating a bacterial infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I as described herein or a pharma- ceutically acceptable salt thereof. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the Acinetobacter, Staphylococcus and / or Mycobacteria genera. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the A. baumannii species, and / or the S. aureus species, and / or the nontuberculous mycobacteria genus, preferably M. abscessus. In a preferred embodiment, the bacterial infection is caused by one or more bacteria belonging to the nontuberculous mycobacteria genus, preferably M. abscessus. In some embodiments, the infection is caused by one or more bacteria belonging to the genus Acinetobacter and / or Staphylococcus, preferably A. baumannii and / or S. aureus.

[0011] The present invention provides rifabutin analogs modified at C25 and pharmaceutical compositions thereof.The compounds of the present invention exhibit broad antibacterial activity against a wide range of bacterial species, thus maintaining the broad antibacterial activity characteristic of the rifamycin class of antibiotics.Further features and advantages of the present technology will be apparent to those skilled in the art upon reading the following detailed description. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The present invention provides analogs of rifabutin that are effective in the treatment of bacterial infections, preferably bacterial infections caused by one or more bacteria belonging to the nontuberculous Mycobacteria genus, preferably M. abscessus.

[0013] Details of the technology are described in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the technology, exemplary methods and materials are now described. Other features, objects, and advantages of the invention will be apparent from the description and claims.

[0014] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0015] The articles "a" and "an" are used in this disclosure to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article, unless the context clearly dictates otherwise. By way of example, "an element" means one element or more than one element.

[0016] The term "and / or" is used in this disclosure to mean either "and" or "or," unless otherwise indicated.

[0017] The term "optionally substituted" is understood to mean that a given chemical moiety (e.g., an alkyl group) can (but is not required to) be bonded to other substituents (e.g., heteroatoms). For example, an optionally substituted alkyl group can be a fully saturated alkyl chain (i.e., pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have a substituent other than hydrogen. For example, it can be bonded at any point along the chain to a halogen atom, a hydroxyl group, or any other substituent described herein. Thus, the term "optionally substituted" means that a given chemical moiety has the potential to contain other functional groups, but does not necessarily have additional functional groups.

[0018] The term "alkyl" refers to a straight or branched chain saturated hydrocarbon. A C1-C6 alkyl group contains 1 to 6 carbon atoms. Examples of -C1-C6 alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl, sec-butyl and tert-butyl, isopentyl and neopentyl.

[0019] The term "alkylene" or "alkylenyl" as used herein refers to a biradical of a straight or branched hydrocarbon chain derived from an alkyl, as defined herein, in which one hydrogen of the alkyl is broken to produce a second radical of alkylene. Examples of alkylene are, by way of illustration, -CH-, -CH-CH-, -CH(CH)-, -CH-CH-CH-, -CH(CH)-CH-, or -CH(CHCH)-.

[0020] The term "cycloalkyl" means a mono- or polycyclic saturated carbocyclic ring containing from 3 to 6 carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0021] The term "aryl" refers to cyclic aromatic hydrocarbon groups having one to two aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. 10 An aryl group contains 6 to 10 carbon atoms. When containing two aromatic rings (such as bicyclic), the aromatic rings of the aryl group may be linked at a single point (e.g., biphenyl) or fused (e.g., naphthyl). An aryl group is optionally substituted at any point of attachment with one or more substituents, e.g., 1 to 5 substituents. Exemplary substituents include, but are not limited to, -H, -halogen, -O-C1-C6 alkyl, -C1-C6 alkyl, -OH, -NH2, -NH(C1-C6 alkyl), and -N(C1-C6 alkyl)2. The substituents (e.g., alkyl groups) can themselves be optionally substituted.

[0022] Unless otherwise specifically defined, "heteroaryl" means a monovalent monocyclic or bicyclic aromatic radical of 5 to 15 ring atoms containing one or more ring heteroatoms selected from N, S, P and O, with the remaining ring atoms being C. Preferably, the heteroatoms are selected from N, S and O, more preferably N and O. A 5-10 membered heteroaryl group contains 5 to 10 atoms. The aromatic radical is optionally substituted independently with one or more substituents described herein.Examples include furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, quinolyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, 1,3-dihydro-2H-benzimidazol-2-one, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[1,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo [1,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, benzofuran, quinolinonyl, isoquinolinyl, 1,6-naphthyridinyl, thieno[3,2-b]pyrazinyl, quinazolinyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a ]pyridinyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, benzoxazolyl, benzisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [1,2,4]triazolo[1,5- a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, thiazolo[5,4-d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, and thieno[2,3-b]pyrrolyl.

[0023] The terms "heterocyclyl" or "heterocycloalkyl" or "heterocycle" refer to monocyclic or polycyclic saturated or partially saturated 3-15 membered ring systems containing carbon and heteroatoms derived from O, N, and S (preferably O and N), and in which at least one ring does not contain delocalized π-electrons (aromaticity) shared between the ring carbons or heteroatoms. 3-10 membered heterocycloalkyl groups contain 3-10 atoms. Heterocyclyl rings include, but are not limited to, oxetanyl, azetadinyl, tetrahydrofuranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, [1,4]diazepane, [1,2]diazepane, decahydro-[1,6]naphthyridine, and diazepinyl.

[0024] Heterocyclyl or heterocycloalkyl rings can also be fused or bridged, for example, bicyclic or tricyclic rings. Furthermore, when containing two or more fused rings, heterocycloalkyl groups as defined herein can have unsaturated or partially saturated rings fused with aromatic and / or heteroaromatic rings. Exemplary ring systems of such heterocyclyl-aryl or heterocyclyl-heteroaryl groups understood herein as embodiments of heterocyclyl groups include indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-1H-isoquinolinyl, 2,3-dihydrobenzofuran, 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazine, and dihydrobenzoxanyl.

[0025] Heterocyclyl or heterocycloalkyl rings can also be spirocyclic heterocycles or spiroheterocycles. As used herein, spirocyclic heterocycles or spiroheterocycles are understood to mean bicyclic or polycyclic ring systems in which at least two rings are bonded through a single atom, and at least one of the rings is a heterocycle (e.g., at least one of the rings is furanyl, morpholinyl or piperazinyl). One or both of the rings of the spiroheterocycle can be fused to one or more additional carbocyclic, heterocyclic, aromatic or heteroaromatic rings to form, for example, a tricyclic ring system in which two of the rings are bonded through a single atom. An exemplary spirocyclic heterocycle of the present invention is 1,3,8-triaza-spiro[4.5]decane.

[0026] As used herein, the term "halo" or "halogen" means fluoro (F), chloro (Cl), bromo (Br), or iodo (I).

[0027] The term "oxo" refers to a carbonyl functional group consisting of a carbon atom double bonded to an oxygen atom. It may be abbreviated herein as "oxo," C(O), or C=O.

[0028] The present invention also includes pharmaceutical compositions comprising an effective amount of the disclosed compounds or pharma- ceutically acceptable salts thereof. Exemplary "pharma-ceutically acceptable salts" include, for example, water-soluble and water-insoluble salts, such as acetate, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzoate, bicarbonate, bisulfate, tartrate, borate, bromide, butyrate, calcium, calcium edetate, camsylate, carbonate, chloride, citrate, clavulariate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycolyl sanilate, hexafluorophosphate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, hydroiodide, setionate, lactate, lactobisulfate, and the like. Examples of salts that may be used include ionate, laurate, magnesium, malate, maleate, mandelate, mesylate, methyl bromide, methyl nitrate, methyl sulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate (1,1-methene-bis-2-hydroxy-3-naphthoate, einbonate), pantothenate, phosphate / diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, acetate, succinate, sulfate, sulfosalicylate, sulamate, tannate, tartrate, theocleate, tosylate, triethiodide, and valerate. 51 R 52 R 53 ] + In some embodiments, X - can be a pharma- ceutically acceptable anion, for example, X - can be any of the anionic species listed above.

[0029] The term "stereoisomers" refers to a set of compounds that have the same number and kinds of atoms and share the same bond connectivity between those atoms, but differ in three-dimensional structure. The term "stereoisomer" refers to any member of this set of compounds.

[0030] The term "diastereomer" refers to a set of stereoisomers that are not superimposable by rotation around a single bond. For example, compounds containing cis- and trans-double bonds, endo- and exo-substitution on a bicyclic ring system, and multiple stereocenters with different relative configurations are considered to be diastereomers. The term "diastereomer" refers to any member of this set of compounds. In some examples presented, the synthetic route may produce a single diastereomer or a mixture of diastereomers. In some cases, these diastereomers were separated, and in other cases, wavy bonds were used to indicate structural elements with variable configuration.

[0031] The term "enantiomers" refers to a pair of stereoisomers that are non-superimposable mirror images of one another. The term "enantiomer" refers to a single member of this pair of stereoisomers. The term "racemic" refers to a 1:1 mixture of a pair of enantiomers.

[0032] The term "tautomer" refers to a set of compounds that have the same number and type of atoms but differ in bond connectivity and are in equilibrium with each other. A "tautomer" is a single member of this set of compounds. Typically, a single tautomer is depicted, but it is understood that this single structure is meant to represent all possible tautomers that may exist. An example includes enol-ketone tautomerism. When a ketone is depicted, it is understood that both the enol form and the ketone form are part of the disclosure.

[0033] The term "solvate" refers to a complex of variable stoichiometry formed by a solute and a solvent. For the purposes of the present invention, such a solvent may not interfere with the biological activity of the solute. Examples of suitable solvents include, but are not limited to, water, MeOH, EtOH, and AcOH. Solvates in which water is the solvent molecule are typically referred to as "hydrates". Hydrates include compositions that contain stoichiometric amounts of water as well as compositions that contain variable amounts of water.

[0034] An "effective amount" when used in reference to a compound is an amount effective to treat or prevent a disease in a subject as described herein.

[0035] The term "carrier" as used in this disclosure encompasses carriers, excipients, and diluents and means a material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, that is involved in carrying or transporting a pharmaceutical agent from one organ or part of the body of a subject to another organ or part of the body.

[0036] The term "treating" with respect to a subject refers to improving at least one symptom of a disorder in a subject. Treating includes curing, ameliorating, or at least partially ameliorating a disorder.

[0037] The term "disorder" is used in this disclosure to mean, and is used interchangeably with, the terms disease, condition, or illness, unless otherwise specified.

[0038] The terms "administer," "administering," or "administration" as used in this disclosure refer to either administering a disclosed compound or a pharma- ceutically acceptable salt of a disclosed compound or composition directly to a subject, or administering to a subject a prodrug derivative or analog of a compound or a pharma- ceutically acceptable salt of the compound or composition, which can form an equivalent amount of the active compound in the subject's body.

[0039] A "patient" or "subject" is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or a non-human primate, e.g., a monkey, chimpanzee, baboon, or rhesus monkey.

[0040] Compounds of the Invention In one aspect, the present invention provides a compound of formula I, or a pharma- ceutically acceptable salt, tautomer, solvate, hydrate, or enantiomer thereof: [ka] During the ceremony, R A and R B are each independently -H, -C1-C6 alkyl, or C3-C6 cycloalkyl; Y is -NR 1 R 2 or [NR 51 R 52 R 53 ] + X - and R 1 and R 2 are each independently -H, -C1-C6 alkyl, -R 3 or -C1-C6-alkylene-R 3 wherein said alkyl and said alkylene are each independently optionally substituted with one or more halogens. R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C6 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C6 alkyl; R 5 and R 6is independently, at each occurrence, -H or -C1-C6 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 3- to 15-membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C6 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C6 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each of -C1-C6 alkyl and -C6-C 10 Aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl; R 51 , R 52 and R 53 are each independently -C1-C6 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C6 alkyl, -OC1-C6 alkyl or -N(C1-C6 alkyl)2; and X - is independently a pharma- ceutically acceptable anion, preferably X - is F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0041] In some embodiments, R A and R B are each independently -H, -C1-C6 alkyl, or C3-C6 cycloalkyl; Y is -NR 1 R 2 or [NR 51 R 52 R 53 ] + X - and R 1 and R 2 are each independently -H, -C1-C6 alkyl, -R 3 or -C1-C6-alkylene-R 3A wherein said alkyl and said alkylene are each independently optionally substituted with one or more halogens. R 3 is 3-10 membered heterocycloalkyl or C6-C 10 aryl, wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C6 alkyl, said alkyl being optionally substituted with one or more halogens; R 3A is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C6 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C6 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C6 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 3- to 15-membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C6 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C6 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each of -C1-C6 alkyl and -C6-C 10 Aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl; R 51 , R 52 and R 53 are each independently -C1-C6 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C6 alkyl, -OC1-C6 alkyl or -N(C1-C6 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0042] In some embodiments, R A and R B are each independently -H, -C1-C6 alkyl, or C3-C6 cycloalkyl; Y is -NR 1 R 2 or [NR 51 R 52 R 53 ] + X - and R 1 and R 2 are each independently -H, -C1-C6 alkyl, -R 3 or -C1-C6-alkylene-R 3wherein the alkyl and alkylene are each independently optionally substituted with one or more halogens. R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C6 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C6 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C6 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C6 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C6 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each of -C1-C6 alkyl and -C6-C 10 Aryl is optionally substituted with one or more halogens; R13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl; R 51 , R 52 and R 53 are each independently -C1-C6 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C6 alkyl, -OC1-C6 alkyl or -N(C1-C6 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0043] In some embodiments, R A and R B are each independently H, -C1-C6 alkyl, or C5-C6 cycloalkyl. In some embodiments, R A and R B are each independently -H or -C1-C6 alkyl. In some embodiments, R A and R B are each independently -H or -C1-C4 alkyl. In some embodiments, R A and R Bare each independently -H or -C1-C2 alkyl. In some preferred embodiments, R A and R B are -H, respectively.

[0044] In some embodiments, R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 wherein said alkyl and said alkylene are each independently optionally substituted with one or more halogens; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C4 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C6 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C6 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 3- to 13-membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C6 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C6 alkyl, -OC1-C6 alkyl or -N(C1-C6 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0045] In some embodiments, R 1 and R 2are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 wherein the alkyl and alkylene are each independently optionally substituted with one or more halogens; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C4 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C4 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C4 alkyl, -OC1-C4 alkyl or -N(C1-C4 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0046] In some embodiments, R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 and; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R14 is independently -H or -C1-C6 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C4 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C4 alkyl, -OC1-C4 alkyl or -N(C1-C4 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0047] In some embodiments, R 1 and R 2 are each independently -H, -R 3 or -C1-C4-alkylene-R 3 and; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C4 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C4 alkyl, -CO2-C1-C4 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C4 alkyl; or R 51 , R 52 and R 53taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more halogen, -C1-C4 alkyl, -OC1-C4 alkyl or -N(C1-C4 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0048] In some embodiments, R 1 and R 2 are each independently -H, -R 3 or -C1-C4-alkylene-R 3 and; R 3 is 5-6 membered heterocycloalkyl, phenyl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or phenyl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10is independently -H, -C1-C4 alkyl, or phenyl, each alkyl or phenyl optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C4 alkyl, -CO2-C1-C4 alkyl, phenyl, or -SO2-phenyl; each alkyl or phenyl is optionally substituted with one or more halogens; R 13 is a 3- to 15-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, or a C6-C 10 aryl; each heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more halogen, -C1-C2 alkyl, -OC1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - or H3CC6H4SO3 - It is.

[0049] In some embodiments, R 1 and R 2 are each independently -H, -R 3or -C1-C4-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H, -C1-C4 alkyl, or phenyl; R 11 and R 12 are each independently -H, -C1-C4 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 3- to 15-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, or a phenyl; each heterocycloalkyl, heteroaryl, or phenyl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0050] In some embodiments, R 1 and R 2 are each independently -H, -R 3 or -C1-C3-alkylene-R 3 and R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 and R 12 are each independently -H, -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 6- to 9-membered heterocycloalkyl, a 5- to 9-membered heteroaryl, or a phenyl; each heterocycloalkyl, heteroaryl, or phenyl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I- , F3CSO3 - , or H3CC6H4SO3 - It is.

[0051] In some embodiments, R 1 is H; R 2 are independently -H, -R 3 or -C1-C3-alkylene-R 3 and R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -H, -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 6- to 9-membered heterocycloalkyl, a 5- to 9-membered heteroaryl, or a phenyl; each heterocycloalkyl or heteroaryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens, and each phenyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0052] In some embodiments, R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 6-9 membered heterocycloalkyl, a 5-9 membered heteroaryl, or a phenyl; each heteroaryl is optionally substituted with one or more oxo, halogen, or -C1-C4 alkyl, said alkyl being optionally substituted with one or more halogens, and phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each of which is optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0053] In some embodiments, R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 -, or H3CC6H4SO3 - It is.

[0054] In some embodiments, R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and; R 3 is 1-piperidine, 4-piperidine, 1-piperazine, 4-morpholine, phenyl, -OR 4 , or -NR 5 R 6 wherein each 1-piperidine is optionally substituted at the 4-position with one or more -C1-C4 alkyls, each 4-piperidine is optionally substituted at the 1-position with one or more -C1-C4 alkyls, and each 1-piperazine is optionally substituted at the 4-position with one or more -C1-C4 alkyls; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0055] In some embodiments, R 1 is H; R 2 are independent of each other, -R 3 or -C2-C3-alkylene-R 3 and R 3 is 1-piperidine, 4-morpholine, or -NR 5 R 6 wherein each piperidine is optionally substituted at the 4-position with one or more -C1-C2 alkyl groups; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0056] In some embodiments, R 1 is H; R 2 are independent of each other, -R 3 or -C2-C3-alkylene-R 3 and R 3 is 1-piperidine, 4-morpholine, or -NR 5 R 6 and; R 5 and R 6 is independently, at each occurrence, -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl; R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 -, or H3CC6H4SO3 - It is.

[0057] In some preferred embodiments, Y is -NR 1 R 2 It is.

[0058] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 wherein the alkyl and alkylene are each independently optionally substituted with one or more halogens; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C4 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C6 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C6 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 3- to 13-membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl.

[0059] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 wherein said alkyl and said alkylene are each independently optionally substituted with one or more halogens; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C4 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14or -C1-C6 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C6 alkyl.

[0060] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 and; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each of which is optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C6 alkyl.

[0061] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 are each independently -H, -R 3 or -C1-C4-alkylene-R 3 and; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C4 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C4 alkyl, -CO2-C1-C4 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl.

[0062] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 are each independently -H, -R 3or -C1-C4-alkylene-R 3 and; R 3 is 5-6 membered heterocycloalkyl, phenyl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or phenyl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H, -C1-C4 alkyl, or phenyl, each alkyl or phenyl optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C4 alkyl, -CO2-C1-C4 alkyl, phenyl, or -SO2-phenyl; each alkyl or phenyl is optionally substituted with one or more halogens; R 13 is a 3- to 15-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, or a C6-C 10 aryl; each heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl.

[0063] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 are each independently -H, -R 3 or -C1-C4-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H, -C1-C4 alkyl, or phenyl; R 11 and R 12are each independently -H, -C1-C4 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 3- to 15-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, or a phenyl; each heterocycloalkyl, heteroaryl, or phenyl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl.

[0064] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 are each independently -H, -R 3 or -C1-C3-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12, oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 and R 12 are each independently -H, -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 6- to 9-membered heterocycloalkyl, a 5- to 9-membered heteroaryl, or a phenyl; each heterocycloalkyl, heteroaryl, or phenyl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl.

[0065] In some embodiments, Y is -NR 1 R 2 and; R 1 is H; R 2 are independently -H, -R 3 or -C1-C3-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -H, -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 6- to 9-membered heterocycloalkyl, a 5- to 9-membered heteroaryl, or a phenyl; each heterocycloalkyl or heteroaryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens, and each phenyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl.

[0066] In some embodiments, Y is -NR 1 R 2 and; R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 6-9 membered heterocycloalkyl, a 5-9 membered heteroaryl, or a phenyl; each heteroaryl is optionally substituted with one or more oxo, halogen, or -C1-C4 alkyl, the alkyl is optionally substituted with one or more halogen, and the phenyl is optionally substituted with one or more halogen, -OR 14or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C4 alkyl.

[0067] In some embodiments, Y is -NR 1 R 2 and; R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl.

[0068] In some embodiments, Y is -NR 1 R 2 and; R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and; R 3 is 1-piperidine, 4-piperidine, 1-piperazine, 4-morpholine, phenyl, -OR 4 , or -NR 5 R 6 wherein each 1-piperidine is optionally substituted at the 4-position with one or more -C1-C4 alkyls, each 4-piperidine is optionally substituted at the 1-position with one or more -C1-C4 alkyls, and each 1-piperazine is optionally substituted at the 4-position with one or more -C1-C4 alkyls; R 4 is independently -H or -C1-C2 alkyl; R 5 and R6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl.

[0069] In some embodiments, Y is -NR 1 R 2 and; R1 is H; R 2 are independent of each other, -R 3 or -C2-C3-alkylene-R 3 and; R 3 is 1-piperidine, 4-morpholine, or -NR 5 R 6 wherein each piperidine is optionally substituted at the 4-position with one or more -C1-C2 alkyl groups; R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl.

[0070] In some embodiments, Y is -NR 1 R 2 and; R 1 is H; R 2 are independent of each other, -R 3 or -C2-C3-alkylene-R 3 and; R 3 is 1-piperidine, 4-morpholine, or -NR 5 R 6 and; R 5 and R 6 is independently, at each occurrence, -C1-C2 alkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; R 14 is independently -H or -C1-C2 alkyl.

[0071] In some preferred embodiments, Y is -NR 1 R 2 and; R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 wherein said alkyl and said alkylene are each independently optionally substituted with one or more halogens; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C4 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C6 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C6 alkyl.

[0072] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 wherein said alkyl and said alkylene are each independently optionally substituted with one or more halogens; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more halogens or -C1-C4 alkyl, said alkyl being optionally substituted with one or more halogens; R 4 is independently -H or -C1-C4 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl.

[0073] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 are each independently -H, -C1-C4 alkyl, -R 3 or -C1-C4-alkylene-R 3 and; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl.

[0074] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 are each independently -H, -R 3 or -C1-C4-alkylene-R 3 and; R 3 is 3-10 membered heterocycloalkyl, C6-C 10 Aryl, -OR 4 or -NR 5 R 6 wherein each heterocycloalkyl or aryl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl.

[0075] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 are each independently -H, -R 3 or -C1-C4-alkylene-R 3 and; R 3is 5-6 membered heterocycloalkyl, phenyl, -OR 4 or -NR 5 R 6 wherein preferably each heterocycloalkyl contains 1-3 heteroatoms selected from N and O, preferably 1-2 heteroatoms selected from N and O, and each heterocycloalkyl or phenyl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl.

[0076] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 are each independently -H, -R 3 or -C1-C4-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C4 alkyl; R 4 is independently -H or -C1-C4 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C4 alkyl.

[0077] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 are each independently -H, -R 3 or -C1-C3-alkylene-R 3 and; R3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl.

[0078] In some embodiments, Y is -NR 1 R 2 ;R 1 is H; R 2 are independently -H, -R 3 or -C1-C3-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl.

[0079] In some embodiments, Y is -NR 1 R 2 and; R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and; R 3piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl.

[0080] In some embodiments, Y is -NR 1 R 2 ;R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and; R 3 piperidine, piperazine, morpholine, phenyl, -OR 4 or -NR 5 R 6 wherein each piperidine, piperazine, morpholine, or phenyl is optionally substituted with one or more -C1-C2 alkyl; R 4 is independently -H or -C1-C2 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl.

[0081] In some embodiments, Y is -NR 1 R 2 ;R 1 is H; R 2 are independent of each other, -R 3 or -C1-C3-alkylene-R 3 and; R 3is 1-piperidine, 4-piperidine, 1-piperazine, 4-morpholine, phenyl, -OR 4 , or -NR 5 R 6 wherein each 1-piperidine is optionally substituted at the 4-position with one or more -C1-C4 alkyls, each 4-piperidine is optionally substituted at the 1-position with one or more -C1-C4 alkyls, and each 1-piperazine is optionally substituted at the 4-position with one or more -C1-C4 alkyls; R 4 is independently -H or -C1-C2 alkyl; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl.

[0082] In some embodiments, Y is -NR 1 R 2 ;R 1 is H; R 2 are independent of each other, -R 3 or -C2-C3-alkylene-R 3 and; R 3 is 1-piperidine, 4-morpholine, or -NR 5 R 6 wherein each piperidine is optionally substituted at the 4-position with one or more -C1-C2 alkyls; and R 5 and R 6 is independently, at each occurrence, -H or -C1-C2 alkyl.

[0083] In some embodiments, Y is -NR 1 R 2 ;R 1 is H; R 2 are independent of each other, -R 3 or -C2-C3-alkylene-R 3 and; R 3 is 1-piperidine, 4-morpholine, or -NR 5 R6 and R 5 and R 6 is independently, at each occurrence, -C1-C2 alkyl.

[0084] In some preferred embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 3- to 13-membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each of which is optionally substituted with one or more halogens; and R 14is independently -H or -C1-C6 alkyl.

[0085] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each of which is optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C6 alkyl.

[0086] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C4 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C4 alkyl, -CO2-C1-C4 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C4 alkyl.

[0087] In some embodiments, Y is -NR 1 R 2 and; R1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H, -C1-C4 alkyl, or phenyl, each alkyl or phenyl optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C4 alkyl, -CO2-C1-C4 alkyl, phenyl, or -SO2-phenyl; each alkyl or phenyl is optionally substituted with one or more halogens; R 13 is a 3- to 15-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, or a C6-C 10 aryl; each heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C4 alkyl.

[0088] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H, -C1-C4 alkyl, or phenyl; R 11 and R 12 are each independently -H, -C1-C4 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 3- to 15-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, or a phenyl; each heterocycloalkyl, heteroaryl, or phenyl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C4 alkyl.

[0089] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 and R12 are each independently -H, -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13 is a 6- to 9-membered heterocycloalkyl, a 5- to 9-membered heteroaryl, or a phenyl; each heterocycloalkyl, heteroaryl, or phenyl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C4 alkyl.

[0090] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 are independently -H, -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13is a 6- to 9-membered heterocycloalkyl, a 5- to 9-membered heteroaryl, or a phenyl; each heterocycloalkyl or heteroaryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens, and each phenyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C4 alkyl.

[0091] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl optionally substituted with one or more halogens, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13is a 6-9 membered heterocycloalkyl, a 5-9 membered heteroaryl, or a phenyl; preferably, each heterocycle or heteroaryl contains 1-3 heteroatoms selected from N and O, preferably 1-2 heteroatoms selected from N and O, each heteroaryl is optionally substituted with one or more oxo, halogen, or -C1-C4 alkyl, alkyl is optionally substituted with one or more halogen, and phenyl is optionally substituted with one or more halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C4 alkyl.

[0092] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a 4-13 membered heterocycloalkyl, said heterocycloalkyl being selected from one or more of -C1-C4 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 is independently -C1-C2 alkyl, -CO2-tert-butyl, phenyl optionally substituted with one or more halogens, or -SO2-phenyl; R 13is a heterocycloalkyl selected from piperidine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, piperazine, and morpholine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one, imidazole, pyrrole, pyrazole, pyrazine, pyridine, and indole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C2 alkyl.

[0093] In some preferred embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a piperidine, piperazine or morpholine ring, said piperidine, piperazine or morpholine being selected from one or more of -C1-C6 alkyl, halogen, -OR 10 , -NR 11 R 12 , oxo, -R 13 or -C1-C6 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more halogen or -OH; R 10 are independently -H, -C1-C6 alkyl, or -C6-C 10 aryl, each alkyl or aryl being optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10aryl; each alkyl and aryl is optionally substituted with one or more halogens; R 13 is C3-C6 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C6-C 10 aryl; each cycloalkyl, heterocycloalkyl, heteroaryl or aryl may be selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each of which is optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C6 alkyl.

[0094] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 together with the nitrogen atom to which they are attached form a piperidine, piperazine, or morpholine ring, said piperidine or piperazine being selected from one or more of -C1-C4 alkyl, -OR 10 , -NR 11 R 12 , -R 13 , or -C1-C4 alkylene-R 13 each alkyl or alkylene optionally substituted with one or more -OH; R 10 is independently -H, -C1-C4 alkyl, or phenyl, each alkyl or phenyl optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C4 alkyl (alkyl optionally substituted with one or more halogens), -CO2-tert-butyl, -SO2-phenyl, or phenyl (phenyl optionally substituted with one or more halogens); R 13is a C3-C6 cycloalkyl, a 3- to 15-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, or a phenyl; each cycloalkyl, heterocycloalkyl, heteroaryl, or phenyl is selected from one or more of oxo, halogen, -OR 14 or -C1-C6 alkyl, each of which is optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C4 alkyl.

[0095] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a piperidine, piperazine, or morpholine ring, said piperazine being optionally substituted with one or more phenyl or -C1-C4 alkyl, and said piperidine being optionally substituted with one or more -OR 10 , -NR 11 R 12 , -R 13 , or -C1-C4 alkylene-R 13 each alkylene optionally substituted with one or more -OH; R 10 is independently -H or phenyl, each phenyl optionally substituted with one or more halogens; R 11 and R 12 are each independently -H, -C1-C2 alkyl (alkyl optionally substituted with one or more halogens), -CO2-tert-butyl, -SO2-phenyl, or phenyl (phenyl optionally substituted with one or more halogens); R 13is a 6-9 membered heterocycloalkyl, a 5-9 membered heteroaryl, or a phenyl; preferably, each heterocycle or heteroaryl contains 1-3 heteroatoms selected from N and O, preferably 1-2 heteroatoms selected from N and O, each heteroaryl is optionally substituted with one or more oxo, halogen, or -C1-C4 alkyl, alkyl is optionally substituted with one or more halogen, and phenyl is optionally substituted with one or more halogen, -OR 14 or -C1-C4 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C2 alkyl.

[0096] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a piperidine, piperazine, or morpholine ring, said piperazine being optionally substituted with one or more phenyl or -C1-C4 alkyl, and said piperidine being optionally substituted with one or more -OR 10 , -NR 11 R 12 , -R 13 , or -C1-C4 alkylene-R 13 each alkylene optionally substituted with one or more -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 are independently -H, -C1-C2 alkyl, -CO2-tert-butyl, -SO2-phenyl; R 13is a heterocycloalkyl selected from piperidine and 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one and imidazole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C2 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C2 alkyl.

[0097] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a piperidine, piperazine, or morpholine ring, said piperazine being optionally substituted at the 4-position with phenyl or -C1-C4 alkyl, and said piperidine being optionally substituted at the 4-position with one or more -OR 10 , -NR 11 R 12 , -R 13 , or -C1-C3 alkylene-R 13 each alkylene optionally substituted with one or more -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 are independently -H, -C1-C2 alkyl, -CO2-tert-butyl, -SO2-phenyl; R 13is a heterocycloalkyl selected from piperidine and 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one and imidazole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is optionally substituted with one or more halogens, -OR 14 or -C1-C2 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C2 alkyl.

[0098] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form a piperidine, piperazine, or morpholine ring, said piperazine being optionally substituted at the 4-position with phenyl or -C1-C4 alkyl, and said piperidine being optionally substituted at the 4-position with one or more -OR 10 , -NR 11 R 12 , -R 13 , or -C1-C3 alkylene-R 13 each alkylene optionally substituted with one or more -OH; R 10 is independently -H or phenyl; R 11 is H or -C1-C2 alkyl; R 12 are independently -H, -C1-C2 alkyl, -CO2-tert-butyl, -SO2-phenyl; R 13is a heterocycloalkyl selected from piperidine and 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine; a heteroaryl selected from 1,3-dihydro-2H-benzimidazol-2-one and imidazole; or a phenyl; each heteroaryl is optionally substituted with one or more halogens or -C1-C2 alkyl, and each phenyl is selected from one or more -OR 14 or -C1-C2 alkyl, each alkyl optionally substituted with one or more halogens; and R 14 is independently -H or -C1-C2 alkyl.

[0099] In some preferred embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form an azetidine ring, said azetidine ring being selected from one or more heteroaryl or -NR 11 R 12 is optionally substituted with; and R 11 and R 12 are each independently -H, -C1-C6 alkyl, -CO2-C1-C6 alkyl, -C6-C 10 Aryl, or -SO2-C6-C 10 aryl; each of -C1-C6 alkyl and -C6-C 10 The aryl is optionally substituted with one or more halogens.

[0100] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2 together with the nitrogen atom to which they are attached form an azetidine ring, said azetidine ring being selected from one or more heteroaryl or -NR 11 R 12 is optionally substituted with; and R11 and R 12 are each independently -H, -C1-C6 alkyl, or phenyl; each phenyl is optionally substituted with one or more halogens.

[0101] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 together with the nitrogen atom to which they are attached form an azetidine ring, said azetidine ring containing one or more pyrroles or -NR 11 R 12 is optionally substituted with; and R 11 and R 12 are each independently -H or phenyl; each phenyl is optionally substituted with one or more fluorines.

[0102] In some embodiments, Y is -NR 1 R 2 ;R 1 and R 2 together with the nitrogen atom to which they are attached form an azetidine ring, said azetidine ring containing one or more pyrroles or -NR 11 R 12 is optionally replaced by; R 11 is H; and R 12 is independently -H or phenyl; phenyl is optionally substituted with one or more fluorines.

[0103] In some preferred embodiments, Y is -NR 1 R 2 and; R 1 and R 2together with the nitrogen atom to which they are attached form a heterocycle selected from 1,3,8-triaza-spiro[4.5]decane, decahydro-[1,6]naphthyridine, 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, or [1,4]diazepane, said heterocycle containing one or more oxo, -C1-C6 alkylene R 13 , or R 13 is optionally substituted with; and R 13 is C6-C 10 It is aryl, which is optionally substituted with one or more halogens.

[0104] In some embodiments, Y is -NR 1 R 2 and R 1 and R 2 together with the nitrogen atom to which they are attached form a heterocycle selected from 1,3,8-triaza-spiro[4.5]decane, decahydro-[1,6]naphthyridine, 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, or [1,4]diazepane, said heterocycle containing one or more oxo, -C1-C3 alkylene R 13 , or R 13 is optionally substituted with; and R 13 is phenyl, which is optionally substituted with one or more halogens.

[0105] In some embodiments, Y is -NR 1 R 2 and; R 1 and R 2together with the nitrogen atom to which they are attached form a heterocycle selected from 1,3,8-triaza-spiro[4.5]decane, decahydro-[1,6]naphthyridine, 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, or [1,4]diazepane, wherein the 1,3,8-triaza-spiro[4.5]decane, decahydro-[1,6]naphthyridine, or [1,4]diazepane is selected from one or more oxo, -C1-C2 alkylene R 13 , or R 13 is optionally substituted with; and R 13 is phenyl, which is optionally substituted with one or more fluorines.

[0106] In some preferred embodiments, Y is [NR 51 R 52 R 53 ] + X - It is.

[0107] In some preferred embodiments, Y is [NR 51 R 52 R 53 ] + X - and R 51 , R 52 and R 53 are each independently selected from -H and -C1-C6 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C6 alkyl, -OC1-C6 alkyl or -N(C1-C6 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 -It is.

[0108] In some embodiments, Y is [NR 51 R 52 R 53 ] + X - and R 51 , R 52 and R 53 are each independently selected from -H and -C1-C4 alkyl; or R 51 , R 52 and R 53 together with the nitrogen atom to which they are attached form a 5-10 membered heteroaryl ring, preferably the heteroaryl containing 1-3 heteroatoms selected from N and O, preferably 1-2 heteroatoms selected from N and O, the heteroaryl being optionally substituted with one or more halogen, -C1-C4 alkyl, -OC1-C4 alkyl or -N(C1-C4 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0109] In some preferred embodiments, Y is [NR 51 R 52 R 53 ] + X - and R 51 , R 52 and R 53 are each independently selected from -H and -C1-C6 alkyl; or R 51 , R 52 and R 53taken together with the nitrogen atom to which they are attached form a 6-10 membered heteroaryl ring, said heteroaryl being optionally substituted with one or more halogen, -C1-C6 alkyl, -OC1-C6 alkyl or -N(C1-C6 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0110] In some embodiments, Y is [NR 51 R 52 R 53 ] + X - and R 51 , R 52 and R 53 are each independently selected from -H and -C1-C4 alkyl; or R 51 , R 52 and R 53 together with the nitrogen atom to which they are attached form a 6-10 membered heteroaryl ring, preferably the heteroaryl containing 1-3 heteroatoms selected from N and O, preferably 1-2 heteroatoms selected from N and O, the heteroaryl being optionally substituted with one or more halogen, -C1-C4 alkyl, -OC1-C4 alkyl or -N(C1-C4 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0111] In some embodiments, Y is [NR 51 R 52 R 53 ] + X- and R 51 , R 52 and R 53 are each independently selected from -H and -C1-C4 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more halogen, -C1-C4 alkyl, -OC1-C4 alkyl or -N(C1-C4 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0112] In some embodiments, Y is [NR 51 R 52 R 53 ] + X - and R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more halogen, -C1-C2 alkyl, -OC1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0113] In some embodiments, Y is [NR 51 R 52 R 53 ] + X - and R 51 , R 52 and R 53 are each independently selected from -H and -C1-C2 alkyl; or R 51 , R 52 and R 53 taken together with the nitrogen atom to which they are attached form a 1-pyridinium, said 1-pyridinium being optionally substituted with one or more -C1-C2 alkyl or -N(C1-C2 alkyl)2; and X - is independently F - , Cl - , Br - , I - , F3CSO3 - , or H3CC6H4SO3 - It is.

[0114] In some embodiments, X - is independently a pharma- ceutically acceptable anion. In some embodiments, X - is independently F - , Cl - , Br - , or I - In some embodiments, X - is independently - Or Br - In some embodiments, X - Br - It is.

[0115] In one or more embodiments, Y of the compounds of the invention can form one of the structures selected from Table 1 below. [Table 1-1] [Table 1-2]

[0116] In one or more embodiments of any of the above aspects, the compound of formula I is selected from Table 2 below. Table 2. Exemplary compounds of the present invention (Cpd) [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7]

[0117] In some preferred embodiments of any of the above aspects, the compound of formula I is selected from the group consisting of: [Table 3-1] [Table 3-2] [Table 3-3]

[0118] In one aspect, the present invention provides a pharmaceutical composition comprising at least one compound of formula I according to the present invention, or a pharma- ceutically acceptable salt, tautomer, solvate or hydrate thereof, and a pharma- ceutically acceptable excipient.

[0119] In one aspect, the present invention provides a compound of formula I of the present invention or a pharma- ceutically acceptable salt, tautomer, solvate or hydrate thereof, or a pharmaceutical composition comprising a compound of the present invention, for use in the prophylaxis or treatment of a disease in a subject, preferably an infection, more preferably a bacterial infection, even more preferably a bacterial infection caused by one or more bacteria belonging to the nontuberculous Mycobacteria genus, preferably M. abscessus.

[0120] In one aspect, the invention provides a method of preventing or treating a bacterial infection in a subject in need thereof, comprising administering to the subject an effective amount of a compound of formula I of the invention or a pharma- ceutically acceptable salt, tautomer, solvate or hydrate thereof. In one aspect, the invention provides a method of treating a bacterial infection in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an effective amount of a compound of formula I of the invention or a pharma- ceutically acceptable salt, tautomer, solvate or hydrate thereof.

[0121] In one aspect, the invention provides the use of a compound of formula I of the invention, or a pharma- ceutically acceptable salt, tautomer, solvate or hydrate thereof, in the manufacture of a medicament for preventing or treating a bacterial infection in a subject in need thereof. In one aspect, the invention provides the use of a pharmaceutical composition comprising a compound of the invention, or a pharma- ceutically acceptable salt, tautomer, solvate or hydrate thereof, in the manufacture of a medicament for treating a bacterial infection in a subject in need thereof.

[0122] In some embodiments, the bacterial infection is caused by one or more bacteria belonging to the nontuberculous Mycobacteria genus, preferably M. abscessus, hi some embodiments, the bacterial infection is caused by A. baumannii.

[0123] Methods for synthesizing the disclosed compounds The compounds of the invention can be made by a variety of methods, including standard chemistry, including, but not limited to, those described in the suitable synthetic routes depicted in the schemes set out below.

[0124] The compounds of the present invention can be prepared by methods known in the art of organic synthesis, as illustrated in part by the following synthetic schemes and examples. In the schemes described below, it is fully understood that protecting groups for sensitive or reactive groups are used where necessary according to general principles or chemistry. Protecting groups are manipulated according to standard methods of organic synthesis (TW Greene and PG M Huts, "Protective Groups in Organic Synthesis", Third edition, Wiley, New York 1999). These groups are removed at a convenient stage of the compound synthesis, using methods readily apparent to those skilled in the art. The selected processes as well as the reaction conditions and the order of their execution shall be consistent with the preparation of the compounds of the present invention.

[0125] Those skilled in the art will recognize whether a stereocenter exists in the compound of formula I. Thus, the present invention includes both possible stereoisomers (unless specified in the synthesis), including racemates as well as individual enantiomers and / or diastereomers. If a compound is desired as a single enantiomer or diastereomer, it can be obtained by stereospecific synthesis or by resolution of the final product or any convenient intermediate. Resolution of the final product, intermediate, or starting material can be affected by any suitable method known in the art. See, for example, "Stereochemistry of Organic Compounds" by EL Eliel, SH Wilen, and LN Mander (Wiley-lnterscience, 1994).

[0126] The compounds described herein can be made from commercially available starting materials or can be synthesized using known organic, inorganic and / or enzymatic processes.

[0127] Preparation of compounds The compounds of the present invention can be synthesized according to the steps outlined in general Schemes 1, 2, 3 and 4. Starting materials are either commercially available, or made by known procedures as reported in the literature or as illustrated. Scheme 1. General synthesis of C21-C23-acetal-25-OH rifabutin (I-1) [ka]

[0128] A general method for preparing C21-C23-acetal-25-OH rifabutin is shown in Scheme 1 above. Protection of the C21 and C23 hydroxy groups with dimethoxypropane and camphorsulfonic acid in DMF gave acetal-protected rifabutin. Deacetylation of the protected rifabutin with sodium methoxide in ether gave 25-OH rifabutin with protected C21 and C23 hydroxy groups (I-1). Scheme 2. Preparation of 25-OH Rifabutin Bromoacetate (I-2) [ka]

[0129] The C21-C23 protected 25-OH rifabutin (I-1) can be esterified with an appropriate carboxylic acid anhydride, such as bromoacetic anhydride, in the presence of a suitable base, such as an amine base, for example 4-(dimethylamino)pyridine. Scheme 3. Preparation of deprotected 25-amine conjugated rifabutin [ka]

[0130] The C25-esterified protected rifabutin can be condensed with the appropriate amine in the presence of DIEA in THF. Deprotection of the C21-C23 acetal in the conjugated rifabutin can be achieved by treatment with an acid such as camphorsulfonic acid in water. Scheme 4. Preparation of deprotected 25-ammonium / pyridinium conjugated rifabutin [ka]

[0131] The C25-esterified protected rifabutin can be condensed with an appropriate tertiary amine or pyridine in THF. Deprotection of the C21-C23 acetal in the conjugated rifabutin can be achieved by treatment with an acid such as camphorsulfonic acid in water.

[0132] Antibacterial efficacy of the disclosed compounds The compounds of the present invention are C25 modified analogs of rifabutin that exhibit broad-spectrum antibacterial activity characteristic of the rifamycin class. Additionally, the compounds of the present invention unexpectedly exhibit enhanced antibacterial activity against nontuberculous mycobacteria, including M. abscessus, compared to currently available antibiotics (e.g., rifabutin).

[0133] As shown in Example 5, Table 6 below, compounds of the present invention are effective in inhibiting bacterial growth in strains of S. aureus, M. abscessus, A. baumannii, M. tuberculosis, M. avium, M. kansasii, M. smegmatis, and M. xenopi.

[0134] Rifampicin showed MIC values ​​of over 32 mg / L against M. abscessus and was not considered to be active against M. abscessus strains. Rifabutin, which is not modified at its C25 position, showed moderate activity against the M. abscessus strains tested, with a MIC value of 8 mg / L. In contrast, compounds of the present invention showed MIC values ​​of 0.125-4 mg / L, which corresponds to 2-64 times higher activity than rifabutin. Thus, the present invention teaches compounds that show higher M. abscessus activity than that of antibiotics known in the literature. In some embodiments, the compounds of the present invention can be used to treat M. abscessus infections, preferably M. abscessus infections that are resistant to current antibiotics.

[0135] As also shown in Example 5, Table 6, the compounds of the present invention possessed strong antibacterial activity against A. baumannii, S. aureus, M. tuberculosis, and other nontuberculous mycobacterial species such as M. smegmatis, M. Kansasii, M. avium, and M. xenopi.

[0136] Thus, in some embodiments, the compounds of the present invention can be used to inhibit bacterial infections, preferably infections caused by nontuberculous mycobacteria, more preferably infections caused by M. abscessus. In some embodiments, the compounds of the present invention can be used to inhibit bacterial infections caused by A. baumannii.

[0137] Methods of Use of the Disclosed Compounds One aspect of the present invention relates to a compound of formula I or a pharma- ceutically acceptable salt thereof for use as a medicament. One aspect of the present invention relates to a method of treating a bacterial infection in a patient in need of such treatment, the method comprising administering to the patient a compound of formula I of the present invention. The present invention also relates to a compound of formula I or a pharmaceutical composition as described herein for use in the method of treating a bacterial infection or for use in the manufacture of a medicament for treating a bacterial infection.

[0138] In some embodiments, the infection is caused by Mycobacterium spp., Acinetobacter spp., Clostridium spp., Enterococcus spp., Hemophilus spp., Legionella spp., Neisseria spp., Staphylococcus spp., Streptococcus spp., Listeria monocytogenes, Moraxella catarrhalis, Bacillus spp., Bacteroides spp., Gardnerella vaginalis, or any of a number of other pathogenic bacteria, including but not limited to Mycobacterium spp., Acinetobacter spp., Clostridium spp., Enterococcus spp., Hemophilus spp., Legionella spp., Neisseria spp., Staphylococcus spp., Streptococcus spp., Listeria monocytogenes, Moraxella catarrhalis, Bacillus spp., Bacteroides spp., Gardnerella vaginalis, It is caused by one or more bacteria belonging to the genus Lactobacillus vaginalis, Lactobacillus spp., Mobiluncus spp., Helicobacter pylori, Campylobacter jejuni, Chlamydia trachomatis and / or Toxoplasma gondii.

[0139] In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the Acinetobacter, Staphylococcus and / or Mycobacteria genera. In some preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the A. baumannii species, and / or the S. aureus species, and / or the nontuberculous mycobacteria genus, preferably M. abscessus. In preferred embodiments, the bacterial infection is caused by one or more bacteria belonging to the nontuberculous mycobacteria genus, preferably M. abscessus. In some embodiments, the infection is caused by one or more bacteria belonging to the genus Acinetobacter and / or Staphylococcus, preferably A. baumannii and / or S. aureus.

[0140] In some preferred embodiments, the infection is caused by one or more bacteria belonging to the nontuberculous Mycobacterium genus, preferably M. abscessus, M. avium, M. kansasii, M. smegmatis, M. xenopi and / or M. malmoense, and even more preferably M. abscessus.

[0141] In some embodiments, the infection is caused by one or more bacteria belonging to the species M. abscessus, A. baumannii, and / or S. aureus. In some embodiments, the infection is caused by one or more bacteria belonging to the species M. abscessus. In some embodiments, the infection is caused by one or more bacteria belonging to the species A. baumannii.

[0142] In some preferred embodiments, the compounds of the present invention are used to treat nontuberculous mycobacteria causing nontuberculous mycobacterial lung infections. In some embodiments, the nontuberculous mycobacterium is M. abscessus, M. avium, M. kansasii, M. smegmatis, M. xenopi, and / or M. malmoense. Thus, in some preferred embodiments, the compounds of the present invention are for use in treating nontuberculous mycobacterial lung infections. In some preferred embodiments, the compounds of the present invention are for use in the manufacture of a medicament for treating nontuberculous mycobacterial lung infections. In some preferred embodiments, the present invention provides a method of treating a nontuberculous mycobacterial lung infection in a subject in need of treatment, comprising administering to the subject an effective amount of a compound of the present invention.

[0143] Exemplary pharmaceutical compositions include a compound of the invention and a pharma- ceutically acceptable carrier, such as a) a diluent, such as purified water, a triglyceride oil, such as hydrogenated or partially hydrogenated vegetable oil, or a mixture thereof, corn oil, olive oil, sunflower oil, safflower oil, fish oil, such as EPA or DHA, or an ester or triglyceride thereof, or a mixture thereof, omega-3 fatty acids or derivatives thereof, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, sodium, saccharin, glucose, and / or glycine; b) a lubricant, such as silica, talcum, stearic acid, its magnesium or calcium salts, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate ... for tablets also; c) binders, for example magnesium aluminium silicate, starch paste, gelatine, tragacanth, methylcellulose, sodium carboxymethylcellulose, magnesium carbonate, natural sugars such as glucose or β-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, waxes and / or polyvinylpyrrolidone (optional); d) disintegrants, for example starch, agar, methylcellulose, bentonite, xanthan gum, alginic acid or its sodium salt, or effervescent mixtures; e) absorbents, colouring agents, flavourings and sweetening agents; f) emulsifiers or dispersing agents, for example Tween and / or g) tablets and gelatin capsules containing an agent that enhances absorption of the compound, such as cyclodextrin, hydroxypropyl cyclodextrin, PEG 400, PEG 200, or other acceptable emulsifiers such as cyclodextrin, hydroxypropyl cyclodextrin, PEG 400, PEG 200.

[0144] The compounds and pharmaceutical compositions of the present invention may be administered by any suitable route, for example orally as a syrup, tablet, capsule, lozenge, controlled release preparation, fast dissolving preparation or lozenge.

[0145] Liquids, particularly injectable compositions, can be prepared, for example, by dissolving, dispersing, etc. For example, the disclosed compounds are dissolved or mixed in a pharma- ceutically acceptable solvent, such as, for example, water, saline, aqueous dextrose, glycerol, ethanol, and the like, thereby forming an injectable isotonic solution or suspension. Proteins, such as albumin, chylomicron particles, or serum proteins, can be used to solubilize the disclosed compounds.

[0146] The disclosed compounds can also be formulated as suppositories which can be prepared from fatty emulsions or suspensions using polyalkylene glycols, for example propylene glycol, as the carrier.

[0147] The disclosed compounds can also be administered in the form of liposome delivery system, for example, small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles.Liposomes can be formed from various phospholipids containing cholesterol, stearylamine or phosphatidylcholine.In some embodiments, a film of lipid components is hydrated with an aqueous solution of drug to form a lipid layer that encapsulates the drug, as described in U.S. Patent No. 5,262,564.

[0148] Injectable parenteral dosages are generally used for subcutaneous, intramuscular or intravenous injection and infusion. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, or in solid forms suitable for dissolving in liquid prior to injection.

[0149] Another aspect of the invention relates to a pharmaceutical composition comprising a compound of the invention and a pharma- ceutically acceptable carrier, which may further comprise an excipient, diluent or surfactant.

[0150] The compositions can be prepared according to conventional mixing, granulating or coating methods, respectively, and the pharmaceutical compositions can contain about 0.1% to about 99%, about 5% to about 90%, or about 1% to about 20% of the disclosed compound by weight or volume.

[0151] Dosage regimens utilizing the disclosed compounds are selected according to a variety of factors, including the type, species, age, weight, sex, and medical condition of the patient; the severity of the condition being treated; the route of administration; the renal or hepatic function of the patient; and the particular disclosed compound being used. A physician or veterinarian of ordinary skill in the art can readily determine and prescribe the effective amount of the drug required to prevent, counter, or arrest the progress of the condition.

[0152] The effective dosage of the disclosed compounds, when used for the indicated effects, ranges from about 0.5 mg to about 5000 mg of the disclosed compounds, as needed to treat the condition. Compositions for in vivo or in vitro use may contain about 0.5, 5, 20, 50, 75, 100, 150, 250, 500, 750, 1000, 1250, 2500, 3500, or 5000 mg of the disclosed compounds, or a range of amounts from one amount to another in the dosage list. In one embodiment, the composition is in the form of a scorable tablet.

[0153] equivalent While the present technology has been described in conjunction with the specific embodiments outlined above, many alternatives, modifications and other variations thereof will be apparent to those skilled in the art, and all such alternatives, modifications and variations are intended to fall within the spirit and scope of the invention. EXAMPLES

[0154] The present invention will now be described by the following non-limiting examples. Specific embodiments of the present invention are described below, but those skilled in the art will understand that various changes and modifications can be made. Reference to preparations carried out in a manner similar to other preparations or by general methods of other preparations may include variations in routine parameters such as slight changes in time, temperature, work-up conditions, amounts of reagents, etc.

[0155] Abbreviation The following list provides definitions of certain abbreviations and symbols used herein. It will be understood that the list is not exhaustive, but the meanings of abbreviations and symbols not defined below herein will be readily apparent to one of ordinary skill in the art. In describing the present invention, elements are identified according to the Periodic Table of the Elements. [Table 4]

[0156] Unless otherwise stated, the purity and identity of intermediates or example compounds were assessed by state-of-the-art HLPC-MS. Methods are described below.

[0157] Compound characterization HPLC analysis Reaction monitoring and compound purity determination were performed by liquid chromatography / mass spectrometry (LC / MS) as follows: HPLC system: Waters 2695 LC equipped with a photodiode array detector Waters 996; Column: XBridge C18 column (particle size 3.5 μm, dimensions 50 mm×4.6 mm); Mobile phase: Phase A (HO / ammonium formate, pH 3.75 (A) or 9.2 (B)) and Phase B (CH3CN+5% HO / ammonium formate, pH 3.75 (A) or 9.2 (B)) were used according to the following method: [Table 5]

[0158] Method A was used for intermediates. Method B was used to determine final compound purity.

[0159] mass spectrometry analysis Mass spectrometer: Waters Alliance Micromass ZQ 2000. Ionization: electrospray (polarity: negative, positive).

[0160] Purity (%) was determined by reversed-phase HPLC with UV detection (254 nm). Structures were confirmed by MS using electrospray ionization positive ion (ESI+) techniques and are given by [M+H] referring to the protonated molecular ion. + reported as.

[0161] NMR analysis NMR spectra were recorded on a Bruker DRX-300 spectrometer. Chemical shifts are in parts per million (ppm). Assignments are one-dimensional (1D) 1 H and 13 C spectra as well as two-dimensional (2D) HSQC and HMBC spectra.

[0162] compound synthesis Example 1 Synthesis of C21-C23 acetal 25-OH rifabutin (I-1) The compounds of the present invention were obtained from free 25-OH rifabutin (intermediate I-1), which was prepared from commercially available rifabutin as shown below. [ka]

[0163] Synthesis of intermediate I-1: Rifabutin (40.0 g, 47.2 mmol) was dissolved in dry DMF (80 mL) at room temperature under nitrogen atmosphere. 2,2-Dimethoxy-propane (58.1 mL, 472 mmol) and camphorsulfonic acid (12.6 g, 54.3 mmol) were added sequentially to the solution. The reaction mixture was stirred at room temperature under nitrogen atmosphere for 26 h. The mixture was then cooled at 0° C. and poured into a mixture of a saturated aqueous solution of NaHCO3 (700 mL) and water (500 mL). The reaction flask was washed with acetone (100 mL). The resulting suspension was stirred on an ice bath for 10 min and filtered. The cake was rinsed with a saturated aqueous solution of NaHCO3 (100 mL) and water (50 mL) and dried under vacuum at 40° C. for 24 h. The crude product was purified by flash chromatography (DCM to 50% mixture DCM / MeOH / NH4OH 90 / 9 / 1.5 in DCM) to give the desired product as a purple solid (37.68 g, 90% yield). LC / MS A(ESI+): tr=3.20 min, m / z[M+H] + =887.48, UV purity: 97% (254nm). 1H NMR (300 MHz, CDCl3):δ 0.39(d, J = 7.0 Hz, 3H), 0.68(d, J = 7.0 Hz, 3H),0.77-0.88 (m, 9H), 0.89-0.98 (m, 6H), 1.23 (s, 3H), 1.36-1.55 (m, 2H), 1.71-2.18 (m, 6H), 1.77 (s, 3H), 1.96 (s, 3H), 2.04 (s, 3H), 2.22-2.35 (m, 3H), 2.31 (s, 3H), 2.52-2.72 (m, 2H), 2.79 (s, 3H), 2.91-3.09 (m, 2H), 3.06 (dd, J = 10.3, 5.4 Hz, 1H), 3.34 (d, J = 6.7 Hz, 1H), 3.58 (dd, J = 3.1 Hz, 1H), 4.91 (d, J = 7.5 Hz, 1H), 5.08(dd, J = 12.1, 6.7 Hz, 1H), 5.87 (d, J = 12.2 Hz, 1H), 6.08 (dd, J = 15.5, 6.8 Hz, 1H), 6.16 (dd, J = 10.7, 1.4 Hz, 1H), 6.28 (dd, J = 15.5, 10.7 Hz, 1H), 7.75 (s, 1H), 8.75 (s, 1H), 14.82 (s, 1H). 13 C NMR(75 MHz,CDCl3):δ 7.89, 9.11, 9.99, 12.8, 18.0, 20.2, 20.3, 20.9, 23.5, 25.8, 34.1, 35.4, 36.0, 36.8, 40.8, 41.4, 51.5, 56.2, 66.3, 71.2, 74.6, 76.9, 78.9, 95.0, 100.1, 104.6, 106.1, 108.7, 111.6, 113.7, 115.3, 123.8, 125.5, 131.2, 132.6, 140.8, 140.9, 142.3, 155.2, 168.2, 168.9, 170.5, 172.2, 181.3, 192.7.

[0164] 21,23-Dimethylacetonide-rifabutin (10.6 g, 11.9 mmol) was dissolved in dry diethyl ether (500 mL). The solution was cooled to -10 °C by Ar bubbling. After 15 min, a solution of NaOMe (30 mL, 25 w% in MeOH) was added slowly. A precipitate formed and another portion of diethyl ether (100 mL) was added to homogenize. NaOMe solution was added again (27.4 mL). The solution was stirred at -5 °C for 10 min, after which the ice bath was removed. The reaction mixture was stirred at room temperature for 6 h. A saturated aqueous solution of NaHCO3 (400 mL) was added and the layers were separated. The aqueous layer was extracted with diethyl ether (400 mL) and the combined organic layers were washed with brine (300 mL) and evaporated to give the desired crude product as a black-purple powder. The product was purified by flash chromatography (DCM to 50% mixture DCM / MeOH / NH4OH 90 / 9 / 1.5 in DCM). After evaporation, the product was redissolved in acetone and slowly added to water with vigorous stirring. The solid was collected by filtration and dried at 40°C to give 8.54 g of deacetylated analog of rifabutin I-1. LC / MS A(ESI+): tr=2.98 min, m / z[M+H] + =845.59, UV purity: 97% (254nm). 1H NMR (300 MHz, CDCl3): δ 0.48 (d, J = 7.0 Hz, 3H), 0.70 (d, J = 6.8 Hz, 3H), 0.74-0.84 (m, 9H), 0.86-0.96 (m, 6H), 1.04 (s, 3H), 1.23-1.33 (m, 1H), 1.43-1.66 (m, 2H), 1.72 (s, 3H), 1.75-2.11 (m, 5H), 2.00 (s, 3H), 2.18-2.29 (m, 3H), 2.21 (s, 3H), 2.47-2.71 (m, 2H), 2.85-3.09 (m, 2H), 3.05-3.14 (m, 1H), 3.10 (s, 3H), 3.27-3.35 (m, 1H), 3.38-3.51 (m, 2H), 3.55 (dd, J = 9.2, 3.3 Hz, 1H), 4.93 (dd, J = 12.5, 9.5 Hz, 1H), 5.93 (dd, J = 15.5, 6.5 Hz, 1H), 6.05-6.16 (m, 2H), 6.24 (dd, J = 15.5, 11.7 Hz, 1H), 7.72 (s, 1H), 8.63 (s, 1H), 14.83 (s, 1H). 13 C NMR (75 MHz, CDCl3): δ 7.7, 8.4, 12.9, 17.8, 19.9, 20.0, 20.9, 21.0, 24.2, 25.5, 25.8, 34.6, 35.2, 36.3, 39.7, 41.1, 51.4, 51.7, 56.2, 66.3, 71.0, 71.5, 75.5, 83.0, 95.0, 99.6, 104.9, 105.7, 108.6, 111.7, 111.8, 114.3, 124.1, 125.5, 132.0, 132.4, 140.3, 142.6, 142.7, 155.2, 168.2, 169.1, 171.3, 181.6, 191.2.

[0165] Example 2 Synthesis of 25-ブロモerinate (I-2)

change

[0166] The following intermediates (shown in Table 3) are obtained using the procedure described in Example 2 for intermediate I-2, substituting the corresponding anhydride, i.e., 2-bromopropanoic anhydride for intermediate I-3 and 2-bromo-2-methylpropanoic anhydride for intermediate I-4, in place of bromoacetic anhydride. [Table 6]

[0167] Example 3 General Procedure for the Preparation of Amine Derivatives A solution of intermediate I-2 in THF (0.035 M) was prepared. The corresponding amine (0.020 mmol, 2 equiv.) was dispensed into a 9 mL Kimble glass tube, and 300 μL of a solution of rifabutin intermediate in THF (corresponding to 1 equiv. of rifabutin intermediate) was added, followed by DIEA (3.54 μL, 0.020 mmol, 2 equiv.). The reactions were stirred at room temperature. After 12 h, 600 μL of an aqueous solution of camphorsulfone (0.5 N) was added to the mixture. The reactions were stirred at room temperature for 12 h. Each mixture was then deposited onto a PoraPak column (Rxn RP 6CC) pre-equilibrated with water. Elution was performed by adding 5 mL of water, 5 mL of a saturated aqueous solution of NaHCO3, 5 mL of a water / ACN (90 / 10) solution, 5 mL of water, and 10 mL of ACN. 10 mL ACN fractions were collected, frozen, and lyophilized to give the desired product as a purple powder.

[0168] Table 4 below summarizes exemplary compounds of the invention that were prepared according to the protocol of Example 3 above. [Table 7-1] [Table 7-2] [Table 7-3] [Table 7-4] [Table 7-5] [Table 7-6] [Table 7-7] [Table 7-8]

Table 7-9

Table 7-10

[0169] Additional analysis (NMR): Cpd#39: 1 H NMR (300 MHz, CDCl3): δ-0.07 (d, J = 7.0 Hz, 3H), 0.58 (d, J = 7.0 Hz, 3H), 0.82 (d, J = 6.9 Hz, 3H), 0.93 (d, J = 6.5 Hz, 6H), 1.00 (d, J = 6.9 Hz, 3H), 1.37-1.47 (m, 1H), 1.65-2.11 (m, 11H), 1.73 (s, 3H), 2.03 (s, 3H), 2.14-2.38 (m, 5H), 2.32 (s, 3H), 2.59-2.80 (m, 2H), 2.76 (s, 3H), 2.90-3.25 (m, 7H), 3.06 (s, 3H), 3.30 (dd, J = 7.5 Hz, 1.8 Hz, 1H), 3.39-3.71 (m, 4H), 4.81 (d, J = 10.5 Hz, 1H), 5.12 (dd, J = 12.5 Hz, 7.6 Hz, 1H), 5.98 (dd, J = 15.5 Hz, 6.6 Hz, 1H), 6.16 (d, J = 12.5 Hz, 1H), 6.20-6.41 (m, 2H), 6.69 (dd, J = 7.4 Hz, 7.4 Hz, 1H), 6.77 (d, J = 8.0 Hz, 2H), 7.16-7.25 (m, 2H), 8.22 (s, 1H), 9.09 (1H), 14.72 (s, 1H). 13C NMR (75 MHz, CDCl3):δ 7.94, 9.02, 11.31, 11.57, 17.63, 20.51, 21.11, 21.12, 22.21, 26.03, 28.99, 29.07, 31.65, 33.29, 35.49, 36.39, 37.96, 38.49, 51.66, 51.70, 53.55, 53.79, 56.67, 57.10, 59.51, 66.49, 72.81, 73.58, 77.11, 81.28, 94.75, 104.87, 107.58, 109.12, 111.99, 113.85, 114.59, 115.69, 117.11, 124.26, 125.35, 129.39, 131.55, 133.22, 141.13, 142.23, 144.82, 150.29, 155.44, 168.45, 168.67, 171.68, 181.30, 192.70. Cpd#40: 1 H NMR (300 MHz, CDCl3):δ-0.06 (d, J = 6.9 Hz, 3H), 0.56 (d, J = 6.4 Hz, 3H), 0.74-1.07 (m, 14H), 1.08-1.30 (m, 4H), 1.34-1.96 (m, 18H), 2.58-2.88 (m, 2H), 2.90-3.18 (m, 6H), 3.25-3.55 (m, 5H), 3.66 (d, J = 9.5 Hz, 1H), 3.84 (s, 1H), 4.60 (d, J = 10.2 Hz, 1H), 4.74 (d, J = 3.03 Hz, 1H), 4.99 (dd, J = 12.2, 6.0 Hz, 1H), 5.96-6.16 (m, 2H), 6.22 (d, J = 10.5 Hz, 1H), 6.40 (dd, J = 15.3, 10.7 Hz, 1H), 8.19 (s, 1H), 8.87 (s, 1H), 14.82 (s, 1H). 13C NMR (75 MHz, CDCl3):δ 7.75, 8.90, 10.4, 11.6, 17.6, 20.4, 20.9, 21.6, 25.7, 26.1, 26.8, 31.8, 33.3, 35.0, 35.9, 37.6, 37.8, 38.5, 44.0, 51.5, 53.4, 53.6, 57.2, 65.6, 66.1, 73.3, 74.6, 79.5, 94.3, 104.9, 107.1, 108.6, 112.0, 114.1, 116.0, 124.4, 125.3, 130.6, 133.4, 141.3, 142.3, 143.1, 155.6, 156.2, 168.4, 171.7, 181.5, 192.7.

[0170] Example 4. General Procedure for the Preparation of Ammonium and Pyridinium Derivatives A solution of intermediate (I-2) in THF (0.07M) was prepared. The corresponding amine or pyridine (0.030mmol, 1.5eq) was dispensed into a 9mL Kimble glass tube and 300μL of a solution of rifabutin intermediate in THF (20mg, 0.020mmol, corresponding to 1eq) was added. The reaction was stirred at 60°C. After 60h, 600μL of an aqueous solution of camphorsulfonic acid (0.5N) was added to the mixture. The reaction was stirred at room temperature for 12h. The mixture was then loaded onto a PoraPak column (Rxn RP 6CC) pre-equilibrated with water. Elution was performed by adding 5mL of water, 5mL of a saturated aqueous solution of NaHCO3, 5mL of a water / ACN (90 / 10) solution and 10mL of ACN. A 10mL ACN fraction was collected, frozen and lyophilized to give the desired product as a purple powder. [Table 8-1] [Table 8-2]

[0171] Example 5 Antibacterial activity MIC values ​​were determined by broth microdilution according to CLSI guidelines. Unless otherwise stated, MICs against A. baumannii were performed in RPMI medium supplemented with 10% FCS. MICs against M. abscessus, M. avium, M. kansasii, M. xenopi, M. tuberculosis, and M. smegmatis were performed in Middlebrook 7H9 broth supplemented with Middlebrook ADC growth supplement. All other MICs were performed in Mueller-Hinton broth adjusted with standard cations.

[0172] The following procedure applies to all species tested except M. avium, M. kansasii, M. xenopi, M. tuberculosis and M. smegmatis. From overnight culture plates (for S. aureus and A. baumannii) or 3-4 day culture plates (for M. abscessus), resuspend cells in 0.9% (w / v) saline and add a bacterial inoculum of 5x10 5 CFU / mL were prepared in the respective test media. Appropriate volumes of 10 mg / mL compound solutions were dispensed directly into 96-well assay plates using a digital dispenser to generate a two-fold dilution series with final concentrations from 32 to 0.002 μg / mL. 100 μL of bacterial suspension was finally added to the compounds. Plates were covered and incubated at 35°C for 20 hours without shaking. All experiments contained antibiotics as quality controls. MICs were determined visually as the lowest concentration of compound that prevented visible growth of bacteria, and plates were scanned for documentation.

[0173] Inocula were prepared from exponentially growing cultures and incubated at an OD of 0.02 for M. tuberculosis and 0.002 for other mycobacteria. 600 A similar procedure was used for M. avium, M. kansasii, M. xenopi, M. tuberculosis and M. smegmatis, except that the incubation time was set at 1 min. Ten three-fold serial dilutions of test compounds were made in duplicate in black Greiner 384-well clear-bottom polystyrene plates (Greiner 781091) using an Echo 550 liquid handler (Labcyte). Plates were inoculated with 50 μl / well of the relevant bacterial culture. MICs were determined at 90% growth inhibition using the GFP reporter for M. tuberculosis and the resazurin assay for other mycobacteria. The incubation period depended on the mycobacterium tested: 7 days for M. avium, M. kansasii and M. xenopi, 5 days for M. tuberculosis and 20 hours for M. smegmatis. Plates were read using a Victor multilabel plate reader (PerkinElmer).

[0174] Activity of the Compounds of the Invention Against S. aureus, A. baumannii, M. abscessus, M. tuberculosis, M. smegmatis, M. kansasii and M. xenopi The in vitro activity of the compounds described herein was determined against S. aureus (strain UAMS-1625), A. baumannii (strain HUMC1), M. abscessus (ATCC 19977), M. tuberculosis H37Rv (ATCC 27294), M. smegmatis (ATCC 700084), M. avium (ATCC 25291), M. kansasii (ATCC 12478), and M. xenopi (ATCC 19250). The results for S. aureus, A. baumannii, M. tuberculosis, M. abscessus, M. smegmatis, M. avium, M. kansasii and M. xenopi are shown in Table 6 below. [Table 9-1] [Table 9-2]

Claims

1. A compound of formula I or a pharmaceutically acceptable salt, tautomer, solvate, hydrate, or enantiomer thereof, 【Chemistry 1】 During the ceremony, R Ａ and R Ｂ These are independently -H and -C １ -C ６ Alkyl or C ３ -C ６ It is a cycloalkyl; Y is -NR １ R ２ or [NR ５１ R ５２ R ５３ ＋ X － and​ R １ and R ２ These are independently -H and -C １ -C ６ Alkyl, -R ３ , or -C １ -C ６ -Alkilen-R ３ The alkyl and alkylene are each independently substituted with one or more halogens of choice. R ３ These are 3-10 member heterocycloalkyl groups, C ６ -C １０ aryl, -OR ４ or -NR ５ R ６ Each heterocycloalkyl or aryl is one or more halogens or -C １ -C ６ It is optionally substituted with an alkyl group, and the alkyl group is optionally substituted with one or more halogens; R ４ These are independently -H or -C １ -C ６ It is alkyl; R ５ and R ６ Independently, in each existence, -H or -C １ -C ６ Is it alkyl? or R １ and R ２ These, together with the nitrogen atoms to which they are bonded, form a 3- to 15-membered heterocycloalkyl group, and the heterocycloalkyl group has one or more -C １ -C ６ Alkyl, halogen, -OR １０ , -NR １１ R １２ , oxo, -R １３ or -C １ -C ６ Alkilen-R １３ They are optionally substituted with; each alkyl or alkylene is optionally substituted with one or more halogens or -OH groups; R １０ These are independently -H and -C １ -C ６ Alkyl, or -C ６ -C １０ It is an aryl group, and each alkyl or aryl group is optionally substituted with one or more halogens; R １１ and R １２ These are independently -H and -C １ -C ６ Alkyl, -CO ２ -C １ -C ６ Alkyl, -C ６ -C １０ Aryl, or -SO ２ -C ６ -C １０ It is an aryl; each -C １ -C ６ Alkyl and -C ６ -C １０ The aryl group is optionally replaced with one or more halogens; R １３ C ３ -C ６ Cycloalkyl, 3-15 member heterocycloalkyl, 5-10 member heteroaryl, or C ６ -C １０ It is an aryl; each cycloalkyl, heterocycloalkyl, heteroaryl, or aryl is one or more oxo, halogen, -OR １４ or -C １ -C ６ It is optionally substituted with alkyl groups, and each alkyl group is optionally substituted with one or more halogens; R １４ These are independently -H or -C １ -C ６ It is alkyl; R ５１ , R ５２ and R ５３ These are, independently, -C １ -C ６ Is it alkyl? or R ５１ , R ５２ and R ５３ together with the nitrogen atom to which they are attached form a 5- to 10-membered heteroaryl, the heteroaryl being optionally substituted with one or more halogens, -C １ -C ６ alkyl, -OC １ -C ６ alkyl or -N(C １ -C ６ alkyl); and ２ optionally substituted with; and X － is, independently, a pharmaceutically acceptable anion, preferably, X － is F － 、Cl － 、Br － 、I － 、F ３ CSO ３ － or H ３ CCO ６ H ４ SO ３ － is, A compound or a pharmaceutically acceptable salt, tautomer, solvate, hydrate, or enantiomer thereof.

2. R Ａ and R Ｂ The compound according to claim 1, wherein each of them is -H.

3. A compound according to claim 1 or claim 2, wherein the formula is: R １ and R ２ These are independently -H and -C １ -C ４ Alkyl, -R ３ , or -C １ -C ４ -Alkilen-R ３ The alkyl and alkylene are each independently and optionally substituted with one or more halogens; R ３ These are 3-10 member heterocycloalkyl groups, C ６ -C １０ aryl, -OR ４ or -NR ５ R ６ Each heterocycloalkyl or aryl is one or more halogens or -C １ -C ４ It is optionally substituted with an alkyl group, and the alkyl group is optionally substituted with one or more halogens; R ４ These are independently -H or -C １ -C ６ It is alkyl; R ５ and R ６ Independently, in each existence, -H or -C １ -C ６ Is it alkyl? or R １ and R ２ These, together with the nitrogen atoms to which they are bonded, form a 3- to 13-membered heterocycloalkyl group, and the heterocycloalkyl group has one or more -C １ -C ４ Alkyl, halogen, -OR １０ , -NR １１ R １２ , oxo, -R １３ or -C １ -C ４ Alkilen-R １３ They are optionally substituted with; each alkyl or alkylene is optionally substituted with one or more halogens or -OH groups; R １０ These are independently -H and -C １ -C ６ Alkyl, or -C ６ -C １０ It is an aryl group, and each alkyl or aryl group is optionally substituted with one or more halogens; R １１ and R １２ These are independently -H and -C １ -C ６ Alkyl, -CO ２ -C １ -C ６ Alkyl, -C ６ -C １０ Aryl, or -SO ２ -C ６ -C １０ It is an aryl group; each alkyl and aryl group is optionally substituted with one or more halogens; R １３ C ３ -C ６ Cycloalkyl, 3-15 member heterocycloalkyl, 5-10 member heteroaryl, or C ６ -C １０ It is an aryl; each cycloalkyl, heterocycloalkyl, heteroaryl, or aryl is one or more oxo, halogen, -OR １４ or -C １ -C ６ It is optionally substituted with alkyl groups, and each alkyl group is optionally substituted with one or more halogens; R １４ These are independently -H or -C １ -C ６ It is alkyl; R ５１ , R ５２ and R ５３ These are, independently, -H and -C １ -C ６ Is it selected from alkyl groups? or R ５１ , R ５２ and R ５３ These, together with the nitrogen atom to which they are bonded, form a 5- to 10-membered heteroaryl ring, and the heteroaryl ring contains one or more halogens, -C １ -C ６ Alkyl, -OC １ -C ６ Alkyl or -N(C) １ -C ６ Alkyl) ２ Replaced by choice; and X － F is independent. － , Cl － , Br － , I － F ３ CSO ３ － or H ３ CC ６ H ４ SO ３ － That is, compound.

4. Y is -NR １ R ２ The compound according to claim 1.

5. Y is -NR １ R ２ And, R １ and R ２ These are independently -H and -C １ -C ４ Alkyl, -R ３ , or -C １ -C ４ -Alkilen-R ３ The alkyl and alkylene are each independently and optionally substituted with one or more halogens; R ３ These are 3-10 member heterocycloalkyl groups, C ６ -C １０ aryl, -OR ４ or -NR ５ R ６ Each heterocycloalkyl or aryl is one or more halogens or -C １ -C ４ It is optionally substituted with an alkyl group, and the alkyl group is optionally substituted with one or more halogens; R ４ These are independently -H or -C １ -C ６ It is alkyl; and R ５ and R ６ Independently, in each existence, -H or -C １ -C ６ The compound according to claim 1, wherein it is alkyl.

6. Y is -NR １ R ２ And, R １ and R ２ These, together with the nitrogen atoms to which they are bonded, form a 3- to 13-membered heterocycloalkyl group, and the heterocycloalkyl group has one or more -C １ -C ４ Alkyl, halogen, -OR １０ , -NR １１ R １２ , oxo, -R １３ or -C １ -C ４ Alkilen-R １３ They are optionally substituted with; each alkyl or alkylene is optionally substituted with one or more halogens or -OH groups; R １０ These are independently -H and -C １ -C ６ Alkyl, or -C ６ -C １０ It is an aryl group, and each alkyl or aryl group is optionally substituted with one or more halogens; R １１ and R １２ These are independently -H and -C １ -C ６ Alkyl, -CO ２ -C １ -C ６ Alkyl, -C ６ -C １０ Aryl, or -SO ２ -C ６ -C １０ It is an aryl group; each alkyl and aryl group is optionally substituted with one or more halogens; R １３ C ３ -C ６ Cycloalkyl, 3-15 member heterocycloalkyl, 5-10 member heteroaryl, or C ６ -C １０ It is an aryl; each cycloalkyl, heterocycloalkyl, heteroaryl, or aryl is one or more oxo, halogen, -OR １４ or -C １ -C ６ They are optionally substituted with alkyl groups, each alkyl group being optionally substituted with one or more halogens; and R １４ These are independently -H or -C １ -C ６ The compound according to claim 1, wherein it is alkyl.

7. Y is -NR １ R ２ And, R １ and R ２ These, together with the nitrogen atoms to which they are bonded, form a piperidine, piperazine, or morpholine ring, and the piperidine, piperazine, or morpholine ring contains one or more -C １ -C ６ Alkyl, halogen, -OR １０ , -NR １１ R １２ , oxo, -R １３ or -C １ -C ６ Alkilen-R １３ They are optionally substituted with; each alkyl or alkylene is optionally substituted with one or more halogens or -OH groups; R １０ These are independently -H and -C １ -C ６ Alkyl, or -C ６ -C １０ It is an aryl group, and each alkyl or aryl group is optionally substituted with one or more halogens; R １１ and R １２ These are independently -H and -C １ -C ６ Alkyl, -CO ２ -C １ -C ６ Alkyl, -C ６ -C １０ Aryl, or -SO ２ -C ６ -C １０ It is an aryl group; each alkyl and aryl group is optionally substituted with one or more halogens; R １３ C ３ -C ６ Cycloalkyl, 3-15 member heterocycloalkyl, 5-10 member heteroaryl, or C ６ -C １０ It is an aryl; each cycloalkyl, heterocycloalkyl, heteroaryl, or aryl is one or more oxo, halogen, -OR １４ or -C １ -C ６ They are optionally substituted with alkyl groups, each alkyl group being optionally substituted with one or more halogens; and R １４ These are independently -H or -C １ -C ６ The compound according to claim 1, wherein it is alkyl.

8. Y is -NR １ R ２ And, R １ and R ２ These, together with the nitrogen atoms to which they are bonded, form an azetidine ring, and the azetidine ring is composed of one or more heteroaryl or -NR １１ R １２ Replaced by choice; and R １１ and R １２ These are independently -H and -C １ -C ６ Alkyl, -CO ２ -C １ -C ６ Alkyl, -C ６ -C １０ Aryl, or -SO ２ -C ６ -C １０ It is an aryl; each -C １ -C ６ Alkyl and -C ６ -C １０ The compound according to claim 1, wherein the aryl is optionally substituted with one or more halogens.

9. Y is -NR １ R ２ And, R １ and R ２ These, together with the nitrogen atoms to which they are bonded, form a heterocycle selected from 1,3,8-triaza-spiro[4.5]decane, decahydro-[1,6]naphthyridine, 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, or [1,4]diazepane, wherein the heterocycle comprises one or more oxo,-C １ -C ６ Alkilen R １３ , or R １３ Replaced by choice; and R １３ C ６ -C １０ The compound according to claim 1, wherein the aryl is optionally substituted with one or more halogens.

10. Y is [NR ５１ R ５２ R ５３ ] ＋ X － And, R ５１ , R ５２ and R ５３ These are, independently, -H and -C １ -C ６ Is it selected from alkyl groups? or R ５１ , R ５２ and R ５３ These, together with the nitrogen atom to which they are bonded, form a 5- to 10-membered heteroaryl ring, and the heteroaryl ring contains one or more halogens, -C １ -C ６ Alkyl, -OC １ -C ６ Alkyl or -N(C) １ -C ６ Alkyl) ２ Replaced by choice; and X － F is independent. － , Cl － , Br － , I － F ３ CSO ３ － or H ３ CC ６ H ４ SO ３ － That is, The compound according to claim 1.

11. A compound according to claim 1, wherein Y is selected from the group consisting of the following. Table 1-1 Table 1-2

12. A compound according to claim 1, selected from the group consisting of the following: Table 2-1 Table 2-2 Table 2-3 Table 2-4 Table 2-5 Table 2-6

13. A compound according to claim 1, selected from the group consisting of the following: Table 3-1 Table 3-2 Table 3-3

14. A pharmaceutical composition comprising at least one compound according to claim 1, or a pharmaceutically acceptable salt, tautomer, solvate or hydrate thereof, and a pharmaceutically acceptable excipient.

15. A compound according to claim 1, or a pharmaceutically acceptable salt, tautomer, solvate, or hydrate thereof, or a pharmaceutical composition according to claim 14, for use as a pharmaceutical.

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