Bipyridine non-covalent dimer cations and uses thereof

Abstract

There is provided a non-covalent dimer cation of bipyridine or a derivative thereof, which is a cation of formula (A), a tautomer thereof, or a stereoisomer thereof. A salt of the present application is provided, comprising a cation of the present application and a first anion. Uses of a cation of the present application or a salt of the present application, for example in the preparation of an antimicrobial agent, are provided. # imgabs0 #

Description

Technical Field

[0001] The present application relates to the field of biomedicine, and more specifically to non-covalent dimer cations of bipyridine or its derivatives and uses thereof, especially in antimicrobial and other aspects. Background Art

[0002] Since cancer patients have low levels of immunity, they are very likely to develop complications of infection, which can affect their survival. At this time, the pathogens that induce complications of infection are not single, and may even include pathogens such as fungi. Currently, there are few drugs in clinical practice that can achieve broad-spectrum antibacterial effects. At the same time, more and more experiments have confirmed that tumor cells are often closely related to the microbial environment, or they coexist with microorganisms, or they promote growth with microorganisms. Therefore, killing tumor cells while eliminating harmful microorganisms during cancer treatment has become one of the key cores of current compound drug development. Summary of the invention

[0003] Provided is a non-covalent dimer cation, comprising a structure of formula (A), a tautomer thereof, or a stereoisomer thereof, or consisting thereof, wherein "-------" in formula (A) is a non-covalent bond,

[0004]

[0005] in,

[0006] Z 7 , Z 8 , and Z 9 It is composed of one nitrogen and two carbons, and Z 17 , Z 18 , and Z 19 It is composed of one nitrogen and two carbons;

[0007] Z 7 R for nitrogen 7 , Z 8 R for nitrogen 8 , Z 9 R for nitrogen 9 , Z 17 R for nitrogen 17 , Z 18 R for nitrogen 18 , and Z 19 R for nitrogen 19 does not exist; and

[0008] R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , Z 7 R for carbon7 , Z 8 R for carbon 8 , Z 9 R for carbon 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , Z 17 R for carbon 17 , Z 18 R for carbon 18 , and Z 19 R for carbon 19 , which are each independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine.

[0009] Provided is a salt of the present application, comprising the cation of the present application and at least one first anion selected from the group consisting of fluoride ion, chloride ion, bromide ion, iodide ion, sulfide ion, nitrate ion, sulfate ion, sulfite ion, thiosulfate ion, persulfate ion, selenate ion, phosphate ion, carbonate ion, hexafluorophosphate ion, hexafluorosilicate ion, acetate ion, sulfonate ion, benzoate ion, and polyphosphate ion.

[0010] Provided is a method for preparing the cation or salt of the present application, comprising: contacting a first reactant with a first acid to obtain a first reactant first acid salt; in an acidic environment, contacting the first reactant first acid salt with a first salt including a first anion to obtain a first solution including a protonated first reactant first acid salt cation and a first anion; and in a strongly reducing and acidic environment, adding a second reactant to the first solution to obtain a second solution or a first intermediate product; and adding a first base to the second solution or contacting the first intermediate product, wherein the first reactant includes a compound of formula (C), and the second reactant includes a compound of formula (D).

[0011]

[0012] Provided is the use of the cation or salt of the present application in preparing a drug, especially in preparing an antimicrobial agent. Provided is a method for preparing a drug, especially an antimicrobial agent, comprising preparing the cation or salt of the present application. DETAILED DESCRIPTION

[0013] As used herein, singular terms refer to one or more than one. For example, "element" or "an element" refers to one element or more than one element. As used herein, the term "plurality" refers to at least two.

[0014] As used herein, the term "about" refers to approximation, in the range of about or near. When the term "about" is used in conjunction with a numerical range, it modifies the range by expanding the limit above or below the provided numerical value. In general, the term "about" is used herein to make the numerical value change 10% above and below the provided value. On the one hand, the term "about" refers to adding or subtracting 20% ​​of the numerical value of the number modified by it. For example, "about 50%" refers to within the range of 45%-55%. The numerical ranges mentioned herein by endpoints include all integers and fractions contained in the range (e.g., "1 to 5" includes 1, 1.5, 2, 2.75, 3, 3.90, 4 and 5). It should also be understood that all integers and fractions thereof are considered to be modified by the term "about".

[0015] As used herein, the terms "comprising", "including", or "containing", as non-exclusive or open terms, are intended to indicate that a combination (e.g., a device, a composition, a method, etc.) includes the listed elements (e.g., each unit of a device, each component of a composition, a substantial step of a method, etc.), but does not exclude other elements. As used herein, the term "substantially consisting of..." when used to define compositions and methods means excluding other elements that have any substantial impact on the combination of the stated purpose, but does not exclude other elements that do not substantially affect the basic and novel features of the present invention. As used herein, the term "consisting of..." refers to a combination (units, components, substantial steps, etc.) excluding other elements, but unless otherwise specified, it is not intended to exclude trace amounts of unavoidable impurities. The embodiments defined by each of these connecting terms are within the scope of the present invention. As a specific embodiment thereof, the technical solution disclosed including the terms "comprising", "including", or "containing" should also be deemed to simultaneously disclose the corresponding technical solutions including the terms "substantially consisting of..." and "consisting of...".

[0016] As used herein, the term "and / or" refers to and encompasses any and all possible combinations of one or more associated listed items. When used in a list of two or more items, the term "and / or" means that any one of the listed items may be included alone, or may include any combination of two or more listed items. For example, if a group, combination, or composition, etc., is described as including (or containing) components A, B, C, and / or D, the composition may include A alone; B alone; C alone; D alone; a combination of A and B; a combination of A and C; a combination of A and D; a combination of B and C; a combination of B and D; a combination of C and D; a combination of A, B and C; a combination of A, B and D; a combination of A, C and D; a combination of B, C and D; or a combination of A, B, C, and D.

[0017] As used herein, the compounds or ions of the present application include a plurality of variable groups. One of ordinary skill in the art will recognize that the combinations of groups contemplated by the present application are chemically permitted combinations of compounds or ions.

[0018] As used herein, the stereochemistry of a chiral center may be defined according to the conventions of those skilled in the art, i.e., using solid lines and wedged bonds. Indicate groups facing out of the page (towards the reader) and use a hashed bond Indicates a group facing inside the paper (the side away from the reader). If such a representation is used, it can be understood to indicate a specific single stereoisomer of the group shown in each chemical structure herein. Any bond not specifically represented by a solid wedge bond or a dotted wedge bond herein should be regarded as not specifically indicating whether the bond faces outside the paper, faces inside the paper, or is located on the paper, but does not prevent it from facing outside the paper or facing inside the paper when chemically allowed.

[0019] As used herein, the term "isomer" means a compound having the same molecular formula but different bonding properties or order of its atoms or the arrangement of its atoms in space. Among them, the term "stereoisomer" means isomers with different arrangements of atoms in space; the term "enantiomer" means stereoisomers with one or more asymmetric centers, which are non-superimposable mirror images of each other; the term "diastereomer" means stereoisomers that do not belong to enantiomers with opposite configurations at one or more asymmetric centers. When a compound has an asymmetric center, for example, if a carbon atom is bonded to four different groups, there can be a pair of enantiomers. Enantiomers can be characterized by the absolute configuration of one or more asymmetric centers and designated as R-configuration or S-configuration, or designated as right-handed or left-handed in the way in which the molecule rotates the plane of polarized light. Chiral compounds can exist as individual enantiomers or as mixtures thereof, for example, as racemic mixtures. The compounds of the present application may contain asymmetric or chiral centers and therefore exist in different stereoisomeric forms. All stereoisomers of the compounds of the present application, including but not limited to diastereomers, enantiomers, and atropisomers, and mixtures thereof such as racemic mixtures, should be considered to form part of the present application.

[0020] As used herein, the term "dimer" generally refers to a complex formed by two molecules or ions, such as bipyridine or its derivatives or protonated ions, through interactions, particularly non-covalent interactions, such as a complex formed by a bipyridine or its derivatives and a protonated ion of a bipyridine or its derivatives. As used herein, the term "n-polymer" generally refers to a complex formed by n molecules or ions, such as bipyridine or its derivatives or protonated ions, through interactions, particularly non-covalent interactions. As used herein, the term "covalent bond" refers to any bond containing or involving electron sharing. Non-limiting examples of covalent bonds include, but are not limited to, peptide bonds, glycosidic bonds, ester bonds, phosphodiester bonds, and particularly include coordinated covalent bonds. As used herein, the term "non-covalent bond" includes any bond or interaction between two or more parts that does not contain or involve electron sharing. Non-limiting examples of non-covalent bonds or interactions include, but are not limited to, electrostatics, π-π effects, van der Waals forces, hydrogen bonds, and hydrophobic effects, particularly hydrogen bonds. As used herein, the term "bonding" includes at least covalent bonds and non-covalent bonds.

[0021] As used herein, the definition of "absence" of a substituent refers to the technical solution of the structure corresponding to the substituent when the substituent is not drawn in the structural formula in which it is located. If the substituent R is "absent", it means that the corresponding structural formula The technical solution of the structure corresponding to the formula; as an example, for the structural formula If the atom Z is nitrogen and the substituent R is "absent", the corresponding structural formula is The technical solution of the corresponding structure.

[0022] As used herein, especially the terms "disclosed or included" as described below, include but are not limited to the disclosure of the specification of the present application (for example, the examples) or the claims, and include but are not limited to the scope of protection requested by the claims of the present application, or the inclusion of any one or more embodiments (for example, the embodiments followed by the terms "in one embodiment" or "in some embodiments" as described herein).

[0023] In order to further explain the technical means and effects adopted by the present application to achieve the predetermined purpose, the specific implementation methods, structures, features and effects of the present application are described in detail below in combination with the preferred embodiments.

[0024] The non-covalent dimer cation of the present application

[0025] On the one hand, the present application provides a non-covalent dimer cation, including the structure of formula (A), its tautomer, or its stereoisomer, or consisting of them, wherein the "-------" in formula (A) should be deemed to include all chemically permitted non-covalent bonds that allow the non-covalent dimer cation of the present application to exist stably in its salt, or to be composed of them.

[0026]

[0027] According to the understanding of those skilled in the art, the non-covalent bond may be understood as a hydrogen bond. However, the applicant has experimentally confirmed that the non-covalent bond can be stably present in a general environment, for example, in the form of a salt; in particular, at least when the mass spectrum is measured, it can still remain stable without breaking, that is, the non-covalent dimer cation of the present application can be kept intact when the mass spectrum is measured, thereby generating the corresponding ion peak of the m / z value of the non-covalent dimer cation of the present application. That is, it should be understood that some properties of hydrogen bonds may be applicable to the non-covalent bond, but the non-covalent bond does not necessarily follow all the understandings of the properties of hydrogen bonds by those skilled in the art, especially in terms of bond energy. In some embodiments, the non-covalent bond is a bond whose bond energy is stronger than that of a general hydrogen bond, for example, a bond with a bond energy greater than 8kJ / mol.

[0028] Although the structure of formula (A) is drawn on a plane, those skilled in the art should understand that the structure of formula (A) is not necessarily a planar structure, and its two bipyridine (or its derivative) parts can be formed at any dihedral angle, as long as the resulting structure is chemically reasonable. Those skilled in the art should also understand that in each bipyridine part in formula (A), the single bond connecting the two pyridine rings should be rotatable; for example, 2,2-bipyridine has at least two different orientations, namely: cis-bipyridine and trans-bipyridine

[0029] In the present application, any disclosure or scope containing any chemical structure having one of the specific cis-bipyridine moieties or trans-bipyridine moieties should also be considered as disclosing or containing the corresponding chemical structure having the other specific cis-bipyridine moiety or trans-bipyridine moiety.

[0030] In some embodiments, Z 7 , Z 8 , and Z 9 In some embodiments, Z 17 , Z 18 , and Z 19 In some embodiments, Z 7 is nitrogen, and Z 8 and Z9 In some embodiments, Z 8 is nitrogen, and Z 7 and Z 9 In some embodiments, Z 9 is nitrogen, and Z 7 and Z 8 In some embodiments, Z 17 is nitrogen, and Z 18 and Z 19 In some embodiments, Z 18 is nitrogen, and Z 17 and Z 19 In some embodiments, Z 19 is nitrogen and Z 17 and Z 18 For carbon.

[0031] In some embodiments, Z 7 is nitrogen, and Z 8 and Z 9 is carbon; and Z 17 is nitrogen, and Z 18 and Z 19 In some embodiments, Z 7 is nitrogen, and Z 8 and Z 9 is carbon; and Z 18 is nitrogen, and Z 17 and Z 19 In some embodiments, Z 7 is nitrogen, and Z 8 and Z 9 is carbon; and Z 19 is nitrogen, and Z 17 and Z 18 In some embodiments, Z 8 is nitrogen, and Z 7 and Z 9 is carbon; and Z 17 is nitrogen, and Z 18 and Z 19 In some embodiments, Z 8 is nitrogen, and Z 7 and Z 9 is carbon; and Z 18 is nitrogen, and Z 17 and Z 19 In some embodiments, Z 8 is nitrogen, and Z 7 and Z 9 is carbon; and Z 19 is nitrogen, and Z 17 and Z 18In some embodiments, Z 9 is nitrogen, and Z 7 and Z 8 is carbon; and Z 17 is nitrogen, and Z 18 and Z 19 In some embodiments, Z 9 is nitrogen, and Z 7 and Z 8 is carbon; and Z 18 is nitrogen, and Z 17 and Z 19 In some embodiments, Z 9 is nitrogen, and Z 7 and Z 8 is carbon; and Z 19 is nitrogen, and Z 17 and Z 18 For carbon.

[0032] In some embodiments, when Z 7 , Z 8 , Z 9 , Z 17 , Z 18 , or Z 19 When it is nitrogen, the corresponding substituent attached thereto, i.e. R 7 , R 8 , R 9 , R 17 , R 18 , or R 19 In some embodiments, Z 7 R for nitrogen 7 , Z 8 R for nitrogen 8 , Z 9 R for nitrogen 9 , Z 17 R for nitrogen 17 , Z 18 R for nitrogen 18 , or Z 19 R for nitrogen 19 , does not exist. In some embodiments, Z 7 R for nitrogen 7 In some embodiments, Z 8 R for nitrogen 8 In some embodiments, Z 9 R for nitrogen 9 In some embodiments, Z 17 R for nitrogen 17 In some embodiments, Z 18 R for nitrogen 18In some embodiments, Z 19 R for nitrogen 19 In some embodiments, Z 7 is nitrogen, and R 7 In some embodiments, Z 8 is nitrogen, and R 8 In some embodiments, Z 9 is nitrogen, and R 9 In some embodiments, Z 17 is nitrogen, and R 17 In some embodiments, Z 18 is nitrogen, and R 18 In some embodiments, Z 19 is nitrogen, and R 19 Does not exist.

[0033] In some embodiments, Z 7 is nitrogen, and R 7 does not exist; and Z 17 is nitrogen, and R 17 In some embodiments, Z 7 is nitrogen, and R 7 does not exist; and Z 18 is nitrogen, and R 18 In some embodiments, Z 7 is nitrogen, and R 7 does not exist; and Z 19 is nitrogen, and R 19 In some embodiments, Z 8 is nitrogen, and R 8 does not exist; and Z 17 is nitrogen, and R 17 In some embodiments, Z 8 is nitrogen, and R 8 does not exist; and Z 18 is nitrogen, and R 18 In some embodiments, Z 8 is nitrogen, and R 8 does not exist; and Z 19 is nitrogen, and R 19 In some embodiments, Z 9 is nitrogen, and R 9 does not exist; and Z 17 is nitrogen, and R 17 In some embodiments, Z 9 is nitrogen, and R 9 does not exist; and Z 18 is nitrogen, and R 18In some embodiments, Z 9 is nitrogen, and R 9 does not exist; and Z 19 is nitrogen, and R 19 Does not exist.

[0034] In some embodiments, Z 7 is nitrogen, R 7 does not exist, and Z 8 and Z 9 is carbon; and Z 17 is nitrogen, R 17 does not exist, and Z 18 and Z 19 In some embodiments, Z 7 is nitrogen, R 7 does not exist, and Z 8 and Z 9 is carbon; and Z 18 is nitrogen, R 18 does not exist, and Z 17 and Z 19 In some embodiments, Z 7 is nitrogen, R 7 does not exist, and Z 8 and Z 9 is carbon; and Z 19 is nitrogen, R 19 does not exist, and Z 17 and Z 18 In some embodiments, Z 8 is nitrogen, R 8 does not exist, and Z 7 and Z 9 is carbon; and Z 17 is nitrogen, R 17 does not exist, and Z 18 and Z 19 In some embodiments, Z 8 is nitrogen, R 8 does not exist, and Z 7 and Z 9 is carbon; and Z 18 is nitrogen, R 18 does not exist, and Z 17 and Z 19 In some embodiments, Z 8 is nitrogen, R 8 does not exist, and Z 7 and Z 9 is carbon; and Z 19 is nitrogen, R 19 does not exist, and Z 17 and Z 18 In some embodiments, Z9 is nitrogen, R 9 does not exist, and Z 7 and Z 8 is carbon; and Z 17 is nitrogen, R 17 does not exist, and Z 18 and Z 19 In some embodiments, Z 9 is nitrogen, R 9 does not exist, and Z 7 and Z 8 is carbon; and Z 18 is nitrogen, R 18 does not exist, and Z 17 and Z 19 In some embodiments, Z 9 is nitrogen, R 9 does not exist, and Z 7 and Z 8 is carbon; and Z 19 is nitrogen, R 19 does not exist, and Z 17 and Z 18 For carbon.

[0035] In some embodiments, Z 7 is nitrogen, R 7 Does not exist, Z 8 and Z 9 is carbon, and R 8 and R 9 is hydrogen; and Z 17 is nitrogen, R 17 Does not exist, Z 18 and Z 19 is carbon, and R 18 and R 19 In some embodiments, Z 7 is nitrogen, R 7 Does not exist, Z 8 and Z 9 is carbon, and R 8 and R 9 is hydrogen; and Z 18 is nitrogen, R 18 Does not exist, Z 17 and Z 19 is carbon, and R 17 and R 19 In some embodiments, Z 7 is nitrogen, R 7 Does not exist, Z 8 and Z 9 is carbon, and R 8 and R 9 is hydrogen; and Z 19 is nitrogen, R19 Does not exist, Z 17 and Z 18 is carbon, and R 17 and R 18 In some embodiments, Z 8 is nitrogen, R 8 Does not exist, Z 7 and Z 9 is carbon, and R 7 and R 9 is hydrogen; and Z 17 is nitrogen, R 17 Does not exist, Z 18 and Z 19 is carbon, and R 18 and R 19 In some embodiments, Z 8 is nitrogen, R 8 Does not exist, Z 7 and Z 9 is carbon, and R 7 and R 9 is hydrogen; and Z 18 is nitrogen, R 18 Does not exist, Z 17 and Z 19 is carbon, and R 17 and R 19 In some embodiments, Z 8 is nitrogen, R 8 Does not exist, Z 7 and Z 9 is carbon, and R 7 and R 9 is hydrogen; and Z 19 is nitrogen, R 19 Does not exist, Z 17 and Z 18 is carbon, and R 17 and R 18 In some embodiments, Z 9 is nitrogen, R 9 Does not exist, Z 7 and Z 8 is carbon, and R 7 and R 8 is hydrogen; and Z 17 is nitrogen, R 17 Does not exist, Z 18 and Z 19 is carbon, and R 18 and R 19 In some embodiments, Z 9 is nitrogen, R 9 Does not exist, Z 7 and Z 8 is carbon, and R7 and R 8 is hydrogen; and Z 18 is nitrogen, R 18 Does not exist, Z 17 and Z 19 is carbon, and R 17 and R 19 In some embodiments, Z 9 is nitrogen, R 9 Does not exist, Z 7 and Z 8 is carbon, and R 7 and R 8 is hydrogen; and Z 19 is nitrogen, R 19 Does not exist, Z 17 and Z 18 is carbon, and R 17 and R 18 For hydrogen.

[0036] In some embodiments, formula (A) is selected from the group consisting of formula (A22), formula (A23), formula (A24), formula (A32), formula (A33), formula (A34), formula (A42), formula (A43), and formula (A44),

[0037]

[0038] In some embodiments, formula (A) is formula (A22). In some embodiments, formula (A) is formula (A23). In some embodiments, formula (A) is formula (A24). In some embodiments, formula (A) is formula (A32). In some embodiments, formula (A) is formula (A33). In some embodiments, formula (A) is formula (A34). In some embodiments, formula (A) is formula (A42). In some embodiments, formula (A) is formula (A43). In some embodiments, formula (A) is formula (A44).

[0039] In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , Z 7 R for carbon 7 , Z 8 R for carbon 8 , Z 9 R for carbon 9 , R 11 , R 12 , R 13 , R 14 , R 15, R 16 , Z 17 R for carbon 17 , Z 18 R for carbon 18 , and Z 19 R for carbon 19 , which are each independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine.

[0040] In some embodiments, Z 7 , Z 8 , Z 17 , and Z 18 is carbon, Z 9 and Z 19 is nitrogen, R 9 and R 19 does not exist, and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 7 , Z 8 , Z 17 , and Z 19 is carbon, Z 9 and Z 18 is nitrogen, R 9 and R 18 does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 19Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 7 , Z 8 , Z 18 , and Z 19 is carbon, Z 9 and Z 17 is nitrogen, R 9 and R 17 does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 18 , and R 19 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 7 , Z 9 , Z 17 , and Z 18 is carbon, Z 8 and Z 19 is nitrogen, R 8 and R 19 does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 7 , Z 9 , Z 17 , and Z 19 is carbon, Z 8 and Z 18 is nitrogen, R 8 and R 18does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 19 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 7 , Z 9 , Z 18 , and Z 19 is carbon, Z 8 and Z 17 is nitrogen, R 8 and R 17 does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 18 , and R 19 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 8 , Z 9 , Z 17 , and Z 18 is carbon, Z 7 and Z 19 is nitrogen, R 7 and R 19 does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 11 , R 12 , R13 , R 14 , R 15 , R 16 , R 17 , and R 18 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 8 , Z 9 , Z 17 , and Z 19 is carbon, Z 7 and Z 18 is nitrogen, R 7 and R 18 does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 19 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 8 , Z 9 , Z 18 , and Z 19 is carbon, Z 7 and Z 17 is nitrogen, R 7 and R 17 does not exist, and R where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 18 , and R 19 Each is independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine.

[0041] In some embodiments, R 1is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 1 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 1 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 1 is selected from the group consisting of hydrogen and methyl. 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 For chlorine.

[0042] In some embodiments, R 2 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 2 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 2 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 2 is selected from the group consisting of hydrogen and methyl. 2 In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 For chlorine.

[0043] In some embodiments, R 3 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 3 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 3 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 3 is selected from the group consisting of hydrogen and methyl. 3In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 For chlorine.

[0044] In some embodiments, R 4 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 4 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 4 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 4 is selected from the group consisting of hydrogen and methyl. 4 In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 In some embodiments, R 4 For chlorine.

[0045] In some embodiments, R 5 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 5 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 5 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 5 is selected from the group consisting of hydrogen and methyl. 5 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R5 For chlorine.

[0046] In some embodiments, R 6 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 6 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 6 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 6 is selected from the group consisting of hydrogen and methyl. 6 In some embodiments, R 6 In some embodiments, R 6 In some embodiments, R 6 In some embodiments, R 6 In some embodiments, R 6 In some embodiments, R 6 In some embodiments, R 6 For chlorine.

[0047] In some embodiments, R 7 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 7 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 7 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 7 is selected from the group consisting of hydrogen and methyl. 7 In some embodiments, R 7 In some embodiments, R 7 In some embodiments, R 7 In some embodiments, R 7 In some embodiments, R 7 In some embodiments, R 7 In some embodiments, R 7 In some embodiments, Z 7 R for carbon 7 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 7 R for carbon 7 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 7 R for carbon7 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 7 R for carbon 7 is selected from the group consisting of hydrogen and methyl. 7 R for carbon 7 In some embodiments, Z 7 R for carbon 7 In some embodiments, Z 7 R for carbon 7 In some embodiments, Z 7 R for carbon 7 In some embodiments, Z 7 R for carbon 7 In some embodiments, Z 7 R for carbon 7 In some embodiments, Z 7 R for carbon 7 In some embodiments, Z 7 R for carbon 7 For chlorine.

[0048] In some embodiments, R 8 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 8 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 8 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 8 is selected from the group consisting of hydrogen and methyl. 8 In some embodiments, R 8 In some embodiments, R 8 In some embodiments, R 8 In some embodiments, R 8 In some embodiments, R 8 In some embodiments, R 8 In some embodiments, R 8 In some embodiments, Z 8 R for carbon 8 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 8 R for carbon 8 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine.8 R for carbon 8 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 8 R for carbon 8 is selected from the group consisting of hydrogen and methyl. 8 R for carbon 8 In some embodiments, Z 8 R for carbon 8 In some embodiments, Z 8 R for carbon 8 In some embodiments, Z 8 R for carbon 8 In some embodiments, Z 8 R for carbon 8 In some embodiments, Z 8 R for carbon 8 In some embodiments, Z 8 R for carbon 8 In some embodiments, Z 8 R for carbon 8 For chlorine.

[0049] In some embodiments, R 9 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 9 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 9 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 9 is selected from the group consisting of hydrogen and methyl. 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, R 9 In some embodiments, Z 9 R for carbon 9 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 9 R for carbon 9is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 9 R for carbon 9 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 9 R for carbon 9 is selected from the group consisting of hydrogen and methyl. 9 R for carbon 9 In some embodiments, Z 9 R for carbon 9 In some embodiments, Z 9 R for carbon 9 In some embodiments, Z 9 R for carbon 9 In some embodiments, Z 9 R for carbon 9 In some embodiments, Z 9 R for carbon 9 In some embodiments, Z 9 R for carbon 9 In some embodiments, Z 9 R for carbon 9 For chlorine.

[0050] In some embodiments, R 11 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 11 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 11 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 11 is selected from the group consisting of hydrogen and methyl. 11 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 For chlorine.

[0051] In some embodiments, R 12 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine.12 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 12 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 12 is selected from the group consisting of hydrogen and methyl. 12 In some embodiments, R 12 In some embodiments, R 12 In some embodiments, R 12 In some embodiments, R 12 In some embodiments, R 12 In some embodiments, R 12 In some embodiments, R 12 For chlorine.

[0052] In some embodiments, R 13 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 13 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 13 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 13 is selected from the group consisting of hydrogen and methyl. 13 In some embodiments, R 13 In some embodiments, R 13 In some embodiments, R 13 In some embodiments, R 13 In some embodiments, R 13 In some embodiments, R 13 In some embodiments, R 13 For chlorine.

[0053] In some embodiments, R 14 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 14 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 14 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 14 is selected from the group consisting of hydrogen and methyl. 14 In some embodiments, R 14 In some embodiments, R14 In some embodiments, R 14 In some embodiments, R 14 In some embodiments, R 14 In some embodiments, R 14 In some embodiments, R 14 For chlorine.

[0054] In some embodiments, R 15 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 15 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 15 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 15 is selected from the group consisting of hydrogen and methyl. 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 For chlorine.

[0055] In some embodiments, R 16 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 16 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 16 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 16 is selected from the group consisting of hydrogen and methyl. 16 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 For chlorine.

[0056] In some embodiments, R 17 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 17 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 17 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 17 is selected from the group consisting of hydrogen and methyl. 17 In some embodiments, R 17 In some embodiments, R 17 In some embodiments, R 17 In some embodiments, R 17 In some embodiments, R 17 In some embodiments, R 17 In some embodiments, R 17 In some embodiments, Z 17 R for carbon 17 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 17 R for carbon 17 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 17 R for carbon 17 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 17 R for carbon 17 is selected from the group consisting of hydrogen and methyl. 17 R for carbon 17 In some embodiments, Z 17 R for carbon 17 In some embodiments, Z 17 R for carbon 17 In some embodiments, Z 17 R for carbon 17 In some embodiments, Z 17 R for carbon 17 In some embodiments, Z 17 R for carbon 17 In some embodiments, Z 17 R for carbon 17 In some embodiments, Z 17 R for carbon 17 For chlorine.

[0057] In some embodiments, R 18 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 18 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 18 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 18 is selected from the group consisting of hydrogen and methyl. 18 In some embodiments, R 18 In some embodiments, R 18 In some embodiments, R 18 In some embodiments, R 18 In some embodiments, R 18 In some embodiments, R 18 In some embodiments, R 18 In some embodiments, Z 18 R for carbon 18 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 18 R for carbon 18 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 18 R for carbon 18 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 18 R for carbon 18 is selected from the group consisting of hydrogen and methyl. 18 R for carbon 18 In some embodiments, Z 18 R for carbon 18 In some embodiments, Z 18 R for carbon 18 In some embodiments, Z 18 R for carbon 18 In some embodiments, Z 18 R for carbon 18 In some embodiments, Z 18 R for carbon 18 In some embodiments, Z 18 R for carbon 18 In some embodiments, Z 18 R for carbon 18For chlorine.

[0058] In some embodiments, R 19 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 19 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 19 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 19 is selected from the group consisting of hydrogen and methyl. 19 In some embodiments, R 19 In some embodiments, R 19 In some embodiments, R 19 In some embodiments, R 19 In some embodiments, R 19 In some embodiments, R 19 In some embodiments, R 19 In some embodiments, Z 19 R for carbon 19 is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 19 R for carbon 19 is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 19 R for carbon 19 is selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine. 19 R for carbon 19 is selected from the group consisting of hydrogen and methyl. 19 R for carbon 19 In some embodiments, Z 19 R for carbon 19 In some embodiments, Z 19 R for carbon 19 In some embodiments, Z 19 R for carbon 19 In some embodiments, Z 19 R for carbon 19 In some embodiments, Z 19 R for carbon 19 In some embodiments, Z 19 R for carbon 19 In some embodiments, Z 19R for carbon 19 For chlorine.

[0059] In some embodiments, R 1 and R 8 In some embodiments, R 2 and R 7 In some embodiments, R 3 and R 6 In some embodiments, R 4 and R 5 In some embodiments, R 11 and R 18 In some embodiments, R 12 and R 17 In some embodiments, R 13 and R 16 In some embodiments, R 14 and R 15 In some embodiments, R 1 and R 11 In some embodiments, R 2 and R 12 In some embodiments, R 3 and R 13 In some embodiments, R 4 and R 14 In some embodiments, R 5 and R 15 In some embodiments, R 6 and R 16 In some embodiments, R 7 and R 17 In some embodiments, R 8 and R 18 In some embodiments, R 9 and R 19 In some embodiments, R 1 and R 18 In some embodiments, R 2 and R 17 In some embodiments, R 3 and R 16 In some embodiments, R 4 and R 15 In some embodiments, R 5 and R 14 In some embodiments, R 6 and R 13 In some embodiments, R7 and R 12 In some embodiments, R 8 and R 11 In some embodiments, R 1 , R 8 , R 11 , and R 18 In some embodiments, R 2 , R 7 , R 12 , and R 17 In some embodiments, R 3 , R 6 , R 13 , and R 16 In some embodiments, R 4 , R 5 , R 14 , and R 15 In some embodiments, R 3 , R 4 , R 5 , R 6 , R 13 , R 14 , R 15 , and R 16 same.

[0060] In some embodiments, R 1 and R 8 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 1 and R 8 are the same and are selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chloro. 1 and R 8 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 1 and R 8 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 1 and R 8 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 1 and R 8 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 1 and R 8 Each is selected from the group consisting of hydrogen and methyl.1 and R 8 are the same and are selected from the group consisting of hydrogen and methyl. 1 and R 8 One of them is hydrogen and the other is selected from the group consisting of hydrogen and methyl. 1 and R 8 One of them is hydrogen and the other is methyl. In some embodiments, R 1 and R 8 For hydrogen.

[0061] In some embodiments, R 2 and R 7 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 2 and R 7 are the same and are selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chloro. 2 and R 7 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 2 and R 7 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 2 and R 7 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 2 and R 7 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 2 and R 7 Each is selected from the group consisting of hydrogen, methyl, and hydroxyl. 2 and R 7 are the same and are selected from the group consisting of hydrogen, methyl, and hydroxyl. 2 and R 7 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, and hydroxyl. 2 and R 7 One of them is hydrogen and the other is selected from the group consisting of hydrogen and methyl. 1 and R 8 One of them is hydrogen and the other is selected from the group consisting of hydrogen and hydroxy. 2 and R 7One of them is methyl and the other is selected from the group consisting of hydrogen and methyl. 1 and R 8 One of them is hydroxyl and the other is selected from the group consisting of hydrogen and hydroxyl. 2 and R 7 One of them is hydrogen and the other is methyl. In some embodiments, R 2 and R 7 One of them is hydrogen and the other is hydroxyl. In some embodiments, R 2 and R 7 Each is selected from the group consisting of methyl, amino, and chlorine. 2 and R 7 are the same and are selected from the group consisting of methyl, amino, and chlorine. 2 and R 7 In some embodiments, R 2 and R 7 In some embodiments, R 2 and R 7 In some embodiments, R 2 and R 7 One of them is methyl, and the other is selected from the group consisting of methyl, amino, and chlorine. 2 and R 7 One of them is amino, and the other is selected from the group consisting of methyl, amino, and chlorine. 2 and R 7 One of the two is chlorine, and the other is selected from the group consisting of methyl, amino, and chlorine.

[0062] In some embodiments, R 3 and R 6 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 3 and R 6 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 3 and R 6 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 3 and R 6 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 3 and R 6 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine.3 and R 6 One of the two is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxy, amino, and chlorine.

[0063] In some embodiments, R 4 and R 5 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 4 and R 5 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 4 and R 5 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 4 and R 5 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 4 and R 5 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 4 and R 5 One of the two is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxy, amino, and chlorine.

[0064] In some embodiments, R 11 and R 18 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 11 and R 18 are the same and are selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chloro. 11 and R 18 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 11 and R 18 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 11 and R 18 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 11 and R 18 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 11 and R 18 Each is selected from the group consisting of hydrogen and methyl. 11and R 18 are the same and are selected from the group consisting of hydrogen and methyl. 11 and R 18 One of them is hydrogen and the other is selected from the group consisting of hydrogen and methyl. 11 and R 18 One of them is hydrogen and the other is methyl. In some embodiments, R 11 and R 18 For hydrogen.

[0065] In some embodiments, R 12 and R 17 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 12 and R 17 are the same and are selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chloro. 12 and R 17 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 12 and R 17 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 12 and R 17 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 12 and R 17 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 12 and R 17 Each is selected from the group consisting of hydrogen, methyl, and hydroxyl. 12 and R 17 are the same and are selected from the group consisting of hydrogen, methyl, and hydroxyl. 12 and R 17 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, and hydroxyl. 12 and R 17 One of them is hydrogen and the other is selected from the group consisting of hydrogen and methyl. 11 and R 18 One of them is hydrogen and the other is selected from the group consisting of hydrogen and hydroxy. 12 and R 17 One of them is methyl and the other is selected from the group consisting of hydrogen and methyl.11 and R 18 One of them is hydroxyl and the other is selected from the group consisting of hydrogen and hydroxyl. 12 and R 17 One of them is hydrogen and the other is methyl. In some embodiments, R 12 and R 17 One of them is hydrogen and the other is hydroxyl. In some embodiments, R 12 and R 17 Each is selected from the group consisting of methyl, amino, and chlorine. 12 and R 17 are the same and are selected from the group consisting of methyl, amino, and chlorine. 12 and R 17 In some embodiments, R 12 and R 17 In some embodiments, R 12 and R 17 In some embodiments, R 12 and R 17 One of them is methyl, and the other is selected from the group consisting of methyl, amino, and chlorine. 12 and R 17 One of them is amino, and the other is selected from the group consisting of methyl, amino, and chlorine. 12 and R 17 One of the two is chlorine, and the other is selected from the group consisting of methyl, amino, and chlorine.

[0066] In some embodiments, R 13 and R 16 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 13 and R 16 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 13 and R 16 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 13 and R 16 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 13 and R 16 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 13 and R 16One of the two is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxy, amino, and chlorine.

[0067] In some embodiments, R 14 and R 15 Each is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 14 and R 15 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 14 and R 15 One of them is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine. 14 and R 15 Each is selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 14 and R 15 are the same and are selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine. 14 and R 15 One of the two is hydrogen, and the other is selected from the group consisting of hydrogen, methyl, hydroxy, amino, and chlorine.

[0068] In some embodiments, R 9 and R 19 For hydrogen.

[0069] In some embodiments, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, and R 4 In some embodiments, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, and R 8 In some embodiments, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, and R 14 In some embodiments, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, and R 18 In some embodiments, R 1 Methyl, R 2 is hydrogen, R 3 is hydrogen, and R 4 In some embodiments, R 5 is hydrogen, R 6 is hydrogen, R 7is hydrogen, and R 8 In some embodiments, R 11 Methyl, R 12 is hydrogen, R 13 is hydrogen, and R 14 In some embodiments, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, and R 18 In some embodiments, R 1 is hydroxyl group, R 2 is hydrogen, R 3 is hydrogen, and R 4 In some embodiments, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, and R 8 In some embodiments, R 11 is hydroxyl group, R 12 is hydrogen, R 13 is hydrogen, and R 14 In some embodiments, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, and R 18 In some embodiments, R 1 is hydrogen, R 2 Methyl, R 3 is hydrogen, and R 4 In some embodiments, R 5 is hydrogen, R 6 is hydrogen, R 7 is methyl, and R 8 In some embodiments, R 11 is hydrogen, R 12 Methyl, R 13 is hydrogen, and R 14 In some embodiments, R 15 is hydrogen, R 16 is hydrogen, R 17 is methyl, and R 18 In some embodiments, R 1 is hydrogen, R 2 is amino, R 3 is hydrogen, and R 4 In some embodiments, R 5 is hydrogen, R 6 is hydrogen, R 7 is amino, and R 8 In some embodiments, R 11 is hydrogen, R12 is amino, R 13 is hydrogen, and R 14 In some embodiments, R 15 is hydrogen, R 16 is hydrogen, R 17 is amino, and R 18 In some embodiments, R 1 is hydrogen, R 2 Chlorine, R 3 is hydrogen, and R 4 In some embodiments, R 5 is hydrogen, R 6 is hydrogen, R 7 is chlorine, and R 8 In some embodiments, R 11 is hydrogen, R 12 Chlorine, R 13 is hydrogen, and R 14 In some embodiments, R 15 is hydrogen, R 16 is hydrogen, R 17 is chlorine, and R 18 For hydrogen.

[0070] In some embodiments: R 1 , Z 8 R for carbon 8 , R 11 , and Z 18 R for carbon 18 , are each independently selected from the group consisting of hydrogen and methyl; R 2 , Z 7 R for carbon 7 , R 12 , and Z 17 R for carbon 17 , are each independently selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine; and R 3 , R 4 , R 5 , R 6 , Z 9 R for carbon 9 , R 13 , R 14 , R 15 , R 16 , and Z 19 R for carbon 19 , is hydrogen.

[0071] In some embodiments: R 1 , R 3 , R 4 , R 5 , R6 , Z 8 R for carbon 8 , Z 9 R for carbon 9 , R 11 , R 13 , R 14 , R 15 , R 16 , Z 18 R for carbon 18 , and Z 19 R for carbon 19 , is hydrogen; and R 2 , Z 7 R for carbon 7 , R 12 , and Z 17 R for carbon 17 , are each independently selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine, and at least one of them is selected from the group consisting of hydroxyl, amino, and chlorine.

[0072] In some embodiments, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , Z 7 R for carbon 7 , Z 8 R for carbon 8 , Z 9 R for carbon 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , Z 17 R for carbon 17 , Z 18 R for carbon 18 , and Z 19 R for carbon 19 , is hydrogen.

[0073] In some embodiments: Z 7 , Z 8 , Z 17 , and z 18 is carbon; Z 9 and Z 19 R is nitrogen; 9 and R 19 does not exist; and R 1 , R 2 , R 3 , R4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18 Each is independently selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine.

[0074] In some embodiments: Z 7 , Z 8 , Z 17 , and Z 18 is carbon; Z 9 and Z 19 R is nitrogen; 9 and R 19 Does not exist; R 1 , R 8 , R 11 , and R 18 are each independently selected from the group consisting of hydrogen and methyl; R 2 , R 7 , R 12 , and R 17 are each independently selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine; and R 3 , R 4 , R 5 , R 6 , R 13 , R 14 , R 15 , and R 16 For hydrogen.

[0075] In some embodiments: Z 7 , Z 8 , Z 17 , and Z 18 is carbon; Z 9 and Z 19 R is nitrogen; 9 and R 19 Does not exist; R 1 , R 3 , R 4 , R 5 , R 6 , R 8 , R 11 , R 13 , R 14 , R 15 , R 16 , and R18 is hydrogen; and R 2 , R 7 , R 12 , and R 17 Each is independently selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine, and at least one of them is selected from the group consisting of hydroxyl, amino, and chlorine.

[0076] In this application, any specific R selected in any disclosed or included formula (A) and / or other structural formulas is 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , and / or R 19 The designated chemical structure shall be deemed to further disclose or include the stereoisomers of the designated chemical structure. In the present application, especially in the various embodiments, any chemical structure disclosed or included shall be deemed to further disclose or include the stereoisomers of the chemical structure.

[0077] In the present application, if any one or more chiral centers do not specify their stereochemistry, they shall be deemed to disclose or include various possible stereoisomers and combinations or mixtures thereof. For example, if a chiral center does not specify its stereochemistry, it shall be deemed to disclose or include chemical structures in which the chiral center is (R)-configuration, and chemical structures in which the chiral center is (S)-configuration, and combinations thereof in any proportion, including racemic mixtures. For example, if two chiral centers do not specify their stereochemistry, they shall be deemed to disclose or include chemical structures in which the two chiral centers are (R, R)-configuration, chemical structures in which the two chiral centers are (S, S)-configuration, chemical structures in which the two chiral centers are (R, S)-configuration, and chemical structures in which the two chiral centers are (S, R)-configuration, and combinations thereof in any proportion.

[0078] In this application, any specific R selected in any disclosed or included formula (A) and / or other structural formulas is 1 , R 2 , R 3 , R 4 , R 5 , R6 , R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , and / or R 19 The specified chemical structure shall be deemed to further disclose or include the chemically allowed tautomers of the specified chemical structure. In the present application, particularly in the various embodiments, any chemical structure disclosed or included shall be deemed to further disclose or include the chemically allowed tautomers of the chemical structure.

[0079] Salt of this application

[0080] In one aspect, the present application provides a salt.

[0081] In some embodiments, the salt of the present application includes the non-covalent dimer cation of the present application, and in particular includes the non-covalent dimer cation of the present application and the first anion. For example, the salt of the present application can be represented by formula (B), wherein x is the first anion.

[0082]

[0083] The first anion of the present application enables the cation of the present application to exist stably in the form of salts.

[0084] In some embodiments, formula (B) is selected from the group consisting of formula (B22), formula (B23), formula (B24), formula (B32), formula (B33), formula (B34), formula (B42), formula (B43), and formula (B44),

[0085]

[0086]

[0087] In some embodiments, the first anion (X in formula (B)) includes at least one selected from the group consisting of fluoride ion, chloride ion, bromide ion, iodide ion, sulfide ion, nitrate ion, sulfate ion, sulfite ion, thiosulfate ion, persulfate ion, selenate ion, phosphate ion, carbonate ion, hexafluorophosphate ion, hexafluorosilicate ion, acetate ion, sulfonate ion, benzoate ion, and polyphosphate ion or consists of it. In some embodiments, the first anion includes at least one selected from the group consisting of hexafluorophosphate ion, hexafluorosilicate ion, chloride ion, and sulfate ion or consists of it. In some embodiments, the first anion is fluoride ion. In some embodiments, the first anion is chloride ion. In some embodiments, the first anion is bromide ion. In some embodiments, the first anion is iodide ion. In some embodiments, the first anion is sulfide ion. In some embodiments, the first anion is nitrate ion. In some embodiments, the first anion is sulfate ion. In some embodiments, the first anion is sulfite ion. In some embodiments, the first anion is a thiosulfate ion. In some embodiments, the first anion is a persulfate ion. In some embodiments, the first anion is a selenate ion. In some embodiments, the first anion is a phosphate ion. In some embodiments, the first anion is a carbonate ion. In some embodiments, the first anion is a hexafluorophosphate ion. In some embodiments, the first anion is a hexafluorosilicate ion. In some embodiments, the first anion is an acetate ion. In some embodiments, the first anion is a sulfonate ion, such as an aminosulfonate ion. In some embodiments, the first anion is a benzoate ion. In some embodiments, the first anion is a polyphosphate ion.

[0088] The value of parameter k is obtained according to the valence of the non-covalent dimer cation and the first anion of the present application. In the case where the non-covalent dimer cation of the present application is positively charged with a single valence, the value of parameter k is equal to the valence of the first anion. In some embodiments, k is 1. In some embodiments, k is 2. In some embodiments, k is 3.

[0089] Preparation method of the non-covalent dimer cation of the present application or the salt of the present application

[0090] In some embodiments, a method for preparing a salt comprising a non-covalent dimer cation of the present application, ie, a salt of the present application, may include the following steps.

[0091] Salt formation of the first reactant

[0092] The first reactant is contacted with the first acid. Then, the first reactant first acid salt is obtained. In some embodiments, the first reactant first acid salt comprises the first reactant and the first acid, and / or the protonated first reactant and the conjugate base of the first acid (the first acid conjugate base), or consists of the same.

[0093] In some embodiments, the first reactant comprises or consists essentially of a compound of formula (C), in particular consisting of the compound of formula (C). In some embodiments, the first reactant, the first acid salt, comprises or consists essentially of a salt of formula (C1), in which A is the first acid conjugate base, a is the valence of the first acid conjugate base, and p is H a The equivalent number of A. R in formula (C) or formula (C1) 1 , R 2 , R 3 , R 4 , R 5 , R 6 , Z 7 , Z 8 , and Z 9 , and R if present 7 , R 8 , and R 9 , which may be consistent with the corresponding parts or parameters of the cation (Formula (A)) and salt (Formula (B)) of the embodiments of the present application to be obtained.

[0094]

[0095] In some embodiments, the first reactant is contacted with the first acid in the presence of a first solvent, particularly in the first solvent. In some embodiments, the first acid is selected from at least one of the group consisting of nitric acid, phosphoric acid, sulfuric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid, particularly hydrochloric acid, i.e., the first acid conjugate base (A ion in formula (C1)) is at least one of the group consisting of nitrate ion, phosphate ion, hydrogen phosphate ion, dihydrogen phosphate ion, sulfate ion, hydrogen sulfate ion, fluoride ion, chloride ion, bromide ion and iodide ion, particularly chloride ion. In some embodiments, the first solvent is water. In formula (C1), parameters p and a are obtained corresponding to the type of the first acid. For example, in some embodiments, the first acid is hydrochloric acid, and p is 1.

[0096] As used herein, the term "conjugate acid", when not further defined, includes and refers to the Bronsted-Lowry conjugate acid of the compound to which the term refers, and includes not only the first conjugate acid obtained by the compound gaining a proton, but also the acid obtained by the compound further gaining more protons, if chemically permitted, such as the second conjugate acid obtained by the first conjugate acid further gaining a proton, the third conjugate acid obtained by the second conjugate acid further gaining a proton, etc. As used herein, the term "conjugate base", when not further defined, includes and refers to the Bronsted-Lowry conjugate base of the compound to which the term refers, and includes not only the first conjugate base obtained by the compound losing a proton, but also the base obtained by the compound further losing more protons, if chemically permitted, such as the second conjugate base obtained by the first conjugate base further losing a proton, the third conjugate base obtained by the second conjugate base further losing a proton, etc. For example, the conjugate base of sulfuric acid described herein, when not further defined, should be deemed to include not only hydrogen sulfate ions, but also sulfate ions. For example, the conjugate base of phosphoric acid described herein, unless further limited, should be considered to include not only hydrogen phosphate ions, but also dihydrogen phosphate ions and phosphate ions.

[0097] In some embodiments, the first acid is in excess relative to the first reactant. In some embodiments, the molar ratio of the first reactant to the first acid is 1:2 to 1:10, particularly 1:2.5 to 1:8, more particularly 1:4 to 1:6, and more particularly about 1:5.

[0098] In some embodiments, the concentration of the first acid in the first solvent is greater than 1 M. In some embodiments, the concentration of the first acid in the first solvent is between 1 M and 5 M. In some embodiments, the concentration of the first acid in the first solvent is about 2 M.

[0099] In some embodiments, the contacting of the first reactant with the first acid is at a first temperature. In some embodiments, the first temperature is 0°C to 70°C. In some embodiments, the first temperature is 10°C to 40°C, more particularly 20°C to 30°C, more particularly about 25°C. In some embodiments, the first temperature is 20°C to 50°C, more particularly 30°C to 40°C, more particularly about 37°C. In some embodiments, the first temperature is 0°C to 20°C, more particularly 0°C to 10°C, more particularly about 4°C. In some embodiments, the first temperature is 40°C to 70°C, more particularly 50°C to 60°C, more particularly about 60°C.

[0100] In some embodiments, after the first reactant contacts the first acid, the first reactant is further heated and recrystallized to obtain the first acid salt of the first reactant. In some embodiments, the heating temperature is 70°C to 100°C, particularly 80°C to 90°C, and more particularly about 85°C.

[0101] Protonation of the first reactant, the first acid salt

[0102] In a first acidic environment, the first reactant, the first acid salt, is contacted with a first salt including a first anion, particularly a first cation and a first anion, to obtain a first solution including a protonated first reactant, the first acid salt cation, and the first anion, as shown in formula (C2).

[0103]

[0104] X and k in formula (C2) may be consistent with the corresponding parts or parameters of the desired salt (formula (B)) of the embodiment of the present application.

[0105] In some embodiments, the first salt is selected from at least one of the group consisting of ammonium fluoride, ammonium chloride, ammonium bromide, ammonium iodide, ammonium sulfide, ammonium nitrate, ammonium sulfate, ammonium sulfite, ammonium thiosulfate, ammonium persulfate, ammonium selenate, ammonium phosphate, ammonium carbonate, ammonium hexafluorophosphate, ammonium hexafluorosilicate, ammonium acetate, various ammonium sulfonates, ammonium benzoate, and ammonium polyphosphate or consists thereof. In some embodiments, the first salt is selected from at least one of the group consisting of ammonium hexafluorophosphate, ammonium hexafluorosilicate, ammonium chloride, and ammonium sulfate or consists thereof. In some embodiments, the first salt is ammonium fluoride. In some embodiments, the first salt is ammonium chloride. In some embodiments, the first salt is ammonium bromide. In some embodiments, the first salt is ammonium iodide. In some embodiments, the first salt is ammonium sulfide. In some embodiments, the first salt is ammonium nitrate. In some embodiments, the first salt is ammonium sulfate. In some embodiments, the first salt is ammonium sulfite. In some embodiments, the first salt is ammonium thiosulfate. In some embodiments, the first salt is ammonium persulfate. In some embodiments, the first salt is ammonium selenate. In some embodiments, the first salt is ammonium phosphate. In some embodiments, the first salt is ammonium carbonate. In some embodiments, the first salt is ammonium hexafluorophosphate. In some embodiments, the first salt is ammonium hexafluorosilicate. In some embodiments, the first salt is ammonium acetate. In some embodiments, the first salt is various ammonium sulfonates, such as ammonium sulfamate. In some embodiments, the first salt is ammonium benzoate. In some embodiments, the first salt is ammonium polyphosphate.

[0106] In some embodiments, the first reactant, the first acid salt, is contacted with the first salt in the presence of a second solvent, particularly in the second solvent. In some embodiments, the second solvent is water. In some embodiments, the first cation is an ammonium ion. Here, the ammonium ion as the first cation can serve as a hydrogen donor.

[0107] In some embodiments, the first salt is in excess relative to the first reactant first acid salt. In some embodiments, the molar ratio of the first reactant first acid salt to the first salt is 1:2 to 1:10, particularly 1:2.5 to 1:8, more particularly 1:4 to 1:6, and more particularly about 1:5.

[0108] In some embodiments, the first solution further comprises a first acid conjugate base. In some embodiments, the first solution further comprises a first cation. In some embodiments, the first solution further comprises a second solvent. In some embodiments, the first solution consists essentially of, in particular of, the protonated first reactant first acid salt cation, the first cation, the first anion, the first acid conjugate base, and the second solvent.

[0109] In some embodiments, the first reactant, the first acid salt, is contacted with the first salt at a second temperature. In some embodiments, the second temperature is 0°C to 70°C. In some embodiments, the second temperature is 10°C to 40°C, more particularly 20°C to 30°C, more particularly about 25°C. In some embodiments, the second temperature is 20°C to 50°C, more particularly 30°C to 40°C, more particularly about 37°C. In some embodiments, the second temperature is 0°C to 20°C, more particularly 0°C to 10°C, more particularly about 4°C. In some embodiments, the second temperature is 40°C to 70°C, more particularly 50°C to 60°C, more particularly about 60°C. In some embodiments, the first temperature and the second temperature are equal.

[0110] In some embodiments, the first acidic environment has a pH value less than or equal to 6. In some embodiments, the first acidic environment has a pH value of 4 to 6, particularly 4.5 to 5.5, particularly 4.8 to 5.2, particularly 4.9 to 5.1, and more particularly about 5. Generally speaking, for a weaker acidic or more alkaline first anion, a first acidic environment with a lower pH value is selected. In some embodiments, the first anion is a hexafluorophosphate ion, and the first acidic environment has a pH value of 4 to 6, particularly 4.5 to 5.5, particularly 4.8 to 5.2, particularly 4.9 to 5.1, and more particularly about 5.

[0111] In some embodiments, the first acidic environment is obtained by allowing the first salt to be in a second solvent. In some embodiments, the first acidic environment is obtained by allowing the first salt and an acid consisting of a first anion and a hydrogen ion to be in a second solvent.

[0112] Non-covalent bond formation

[0113] In a second acidic environment, the second reactant is added to the first solution, in particular, contacting the protonated first reactant cation in the first solution. Then a bond is formed to obtain a second solution including the cation of the embodiment of the present application, the first acid salt cation, and the first anion, as shown in the structure of formula (B1).

[0114]

[0115] In some embodiments, the second reactant comprises or consists essentially of, in particular consists of, a compound of formula (D), wherein R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , Z 17 , Z 18 , and Z 19 , and R if present 17 , R 18 , and R 19 , which may be consistent with the desired cation (Formula (A)) and salt (Formula (B)) of the embodiments of the present application.

[0116]

[0117] In some embodiments, the second reactant is in excess relative to the protonated first reactant cation. In some embodiments, the molar ratio of the protonated first reactant cation to the second reactant is 1:1 to 1:2, such as about 1:1.0, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9, or about 1:2.0.

[0118] In some embodiments, the second solution further comprises a first acid conjugate base. In some embodiments, the second solution further comprises a first cation. In some embodiments, the second solution further comprises a second solvent. In some embodiments, the first solution is substantially composed of, in particular, the first acid salt cation of the embodiment of the present application, the first cation, the first anion, the first acid conjugate base, and the second solvent.

[0119] In some embodiments, the adding of the second reactant to the first solution is at a third temperature. In some embodiments, the third temperature is 0°C to 70°C. In some embodiments, the third temperature is 10°C to 40°C, more particularly 20°C to 30°C, more particularly about 25°C. In some embodiments, the third temperature is 20°C to 50°C, more particularly 30°C to 40°C, more particularly about 37°C. In some embodiments, the third temperature is 0°C to 20°C, more particularly 0°C to 10°C, more particularly about 4°C. In some embodiments, the third temperature is 40°C to 70°C, more particularly 50°C to 60°C, more particularly about 60°C. In some embodiments, the first temperature and the third temperature are equal. In some embodiments, the second temperature and the third temperature are equal. In some embodiments, the first temperature, the second temperature, and the third temperature are equal.

[0120] In some embodiments, the second acidic environment has a pH value less than or equal to 6. In some embodiments, the second acidic environment has a pH value of 4 to 6, particularly 4.5 to 5.5, particularly 4.8 to 5.2, particularly 4.9 to 5.1, and more particularly about 5. Generally speaking, for a first anion that is less acidic or more alkaline, a second acidic environment with a lower pH value is selected. In some embodiments, the first anion is a hexafluorophosphate ion, and the second acidic environment has a pH value of 4 to 6, particularly 4.5 to 5.5, particularly 4.8 to 5.2, particularly 4.9 to 5.1, and more particularly about 5. In some embodiments, the pH value of the first acidic environment and the second acidic environment is the same.

[0121] In some embodiments, the second acidic environment is obtained by allowing the first salt to be in a second solvent. In some embodiments, the second acidic environment is obtained by allowing the first salt and the acid composed of the first anion and the hydrogen ion to be in a second solvent. In some embodiments, it also includes adding a reducing agent to the first solution, especially before, after or at the same time as the second reactant is added to the first solution. That is, in some embodiments, the second acidic environment is reducing, especially strongly reducing. Since the non-covalent dimer cation of the present application has a strong reducing power, the addition of a reducing agent helps to reduce the proportion of the non-covalent dimer cation of the present application that is oxidized in the reaction, which is beneficial to improve the yield of the salt of the present application. In some embodiments, the reducing agent includes at least one or more selected from the group consisting of vitamin C, vitamin E and its derivatives.

[0122] In some embodiments, the second solution is also purified to obtain a first intermediate product including a first acid salt cation of the present application embodiment cation and a first anion. In some embodiments, the purification includes dialysis. In some embodiments, the dialysis can be dialyzed by a membrane with a molecular weight cutoff (MWCO) of 50Da to 500Da, particularly about 100Da or 200Da.

[0123] Formation of the salt of the present application

[0124] The first base is added to the second solution or contacted with the first intermediate product to remove the first acid (H in Formula (B1)) in the second solution or the first intermediate product. a A). Then the salt of the present application is obtained.

[0125] In some embodiments, the salt of the present application includes the non-covalent dimer cation of the present application and a first anion. For example, the salt of the present application can be represented by formula (B).

[0126] In some embodiments, the first base includes at least one selected from the group consisting of ammonia, sodium hydroxide, potassium hydroxide, and triethanolamine, or is composed of, but is not limited to this. It should be understood by those skilled in the art that any base that can adjust the pH value to alkalinity and does not undergo further redox reaction can be used as the first base here. In some embodiments, the first base is ammonia, particularly dilute ammonia. In some embodiments, the first base is sodium hydroxide. In some embodiments, the first base is potassium hydroxide. In some embodiments, the first base is triethanolamine.

[0127] In some embodiments, the adding of the first base to the second solution or contacting the first intermediate product is to adjust the pH value of the second solution or the solution including the first intermediate product to alkaline. In some embodiments, the alkalinity is a pH value of 8 or more, particularly a pH value of 8 to 10, particularly 8.5 to 9.5, particularly 8.8 to 9.2, and more particularly about 9.

[0128] In some embodiments, the step of contacting the first intermediate product with the first base comprises contacting the first intermediate product with the first base in water.

[0129] In some embodiments, after adding the first alkali in the second solution, purification is also included to obtain the salt of the present application. In some embodiments, the purification includes dialysis. In some embodiments, the dialysis can be dialyzed by a membrane with a molecular weight cutoff (MWCO) of 50Da to 500Da, particularly about 100Da or 200Da. In some embodiments, the purification includes filtration.

[0130] Use of the non-covalent dimer cation of the present application or the salt of the present application

[0131] In some embodiments, the use of the non-covalent dimer cation of the present application or the salt of the present application in antimicrobial is provided. In some embodiments, the use of the non-covalent dimer cation of the present application or the salt of the present application in the preparation of an antimicrobial agent is provided. In some embodiments, the non-covalent dimer cation of the present application or the salt of the present application for antimicrobial is provided. In some embodiments, an antimicrobial method is provided, comprising applying the non-covalent dimer cation of the present application or the salt of the present application.

[0132] In some embodiments, the microorganism is a bacterium and / or a fungus. In some embodiments, the microorganism is a bacterium. In some embodiments, the bacterium is a gram-positive bacterium. In some embodiments, the bacterium is a gram-negative bacterium. In some embodiments, the bacterium is selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Enterococcus faecalis, Streptococcus mutans, Streptococcus thermophilus, Streptococcus lactis, Streptococcus bovis, Corynebacterium diphtheriae, Listeria monocytogenes, Bacillus subtilis, Bacillus cereus, Clostridium perfringens, Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, and Pseudomonas fluorescens. In some embodiments, the bacterium is selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Enterococcus faecalis, Streptococcus mutans, Streptococcus thermophilus, Streptococcus lactis, Streptococcus bovis, Corynebacterium diphtheriae, Listeria monocytogenes, Bacillus subtilis, Bacillus cereus, and Clostridium perfringens. In some embodiments, the bacterium is selected from the group consisting of Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, and Pseudomonas fluorescens. In some embodiments, the bacterium is Staphylococcus aureus. In some embodiments, the bacterium is Staphylococcus epidermidis. In some embodiments, the bacterium is Staphylococcus haemolyticus. In some embodiments, the bacterium is Enterococcus faecalis. In some embodiments, the bacterium is Streptococcus mutans. In some embodiments, the bacterium is Streptococcus thermophilus. In some embodiments, the bacterium is Streptococcus lactis. In some embodiments, the bacterium is Streptococcus bovis. In some embodiments, the bacterium is Corynebacterium diphtheriae. In some embodiments, the bacterium is Listeria monocytogenes. In some embodiments, the bacterium is Bacillus subtilis. In some embodiments, the bacterium is Bacillus cereus. In some embodiments, the bacterium is Clostridium perfringens. In some embodiments, the bacterium is Escherichia coli. In some embodiments, the bacterium is Salmonella enteritidis. In some embodiments, the bacterium is Klebsiella pneumoniae. In some embodiments, the bacterium is Proteus vulgaris. In some embodiments, the bacterium is Yersinia enterocolitica. In some embodiments, the bacterium is Pseudomonas aeruginosa. In some embodiments, the bacterium is Pseudomonas fluorescens. In some embodiments, the microorganism is a fungus. In some embodiments, the fungus is selected from the group consisting of Cryptococcus neoformans, Candida albicans, Trichophyton rubrum, Malassezia sphericalensis, Malassezia furfur, Aspergillus flavus, and Aspergillus niger. In some embodiments, the fungus is Cryptococcus neoformans. In some embodiments, the fungus is Candida albicans. In some embodiments, the fungus is Trichophyton rubrum. In some embodiments, the fungus is Malassezia globosa. In some embodiments, the fungus is Malassezia furfur.In some embodiments, the fungus is Aspergillus flavus. In some embodiments, the fungus is Aspergillus niger.

[0133] Example

[0134] In the following embodiments, if a compound, including the first reactant, the second reactant, the cation of the embodiment, or the salt of the embodiment, has chirality but the chirality is not explicitly specified, the compound may be a chiral mixture, such as a racemic compound.

[0135] Example 1

[0136] The salt of Example 1 is specifically represented by formula (1). 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 1 9 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0137]

[0138] Preparation method

[0139] The preparation method of the salt of this embodiment is as follows.

[0140] - The first reactant is 2,2′-bipyridine;

[0141] - the second reactant is 2,2′-bipyridine; and

[0142] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0143] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0144] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0145] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0146] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0147] Detection of products or intermediates

[0148] The hydrochloride salt of the first reactant in this example is white crystals with a yield of about 0.8 g and a yield of about 80%.

[0149] The salt yield in this example is about 1.6 g, with a yield of about 85%.

[0150] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0151] Example 2

[0152] The salt of Example 2 is specifically shown in formula (2). That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=2, and X is a hexafluorosilicate ion.

[0153]

[0154] Preparation method

[0155] The preparation method of the salt of this embodiment is as follows.

[0156] - The first reactant is 2,2′-bipyridine;

[0157] - the second reactant is 2,2′-bipyridine; and

[0158] - The first salt is ammonium hexafluorosilicate, that is, the first anion is a hexafluorosilicate ion.

[0159] At 37°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0160] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 37° C. for 12 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0161] 0.8 g of the second reactant was added to the first aqueous solution at 37° C. and gently stirred for 12 hours to obtain a second aqueous solution including the cation of this embodiment. 1 M sodium hydroxide solution was added to adjust the pH value to 9, and the solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da, and dried to obtain the product, i.e., the salt of this embodiment.

[0162] Detection of products or intermediates

[0163] The hydrochloride salt of the first reactant in this example is white crystals with a yield of about 0.8 g and a yield of about 80%.

[0164] The salt yield in this example is about 1.2 g, and the yield is about 63%.

[0165] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0166] Example 3

[0167] The salt of Example 3 is specifically shown in formula (3). That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=2, and X is a sulfate ion.

[0168]

[0169] Preparation method

[0170] The preparation method of the salt of this embodiment is as follows.

[0171] - The first reactant is 2,2′-bipyridine;

[0172] - the second reactant is 2,2′-bipyridine; and

[0173] - The first salt is ammonium sulfate, that is, the first anion is a sulfate ion.

[0174] At 60°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0175] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 2 g of the first salt of this example was added, and stirring was continued at 60° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0176] 0.65 g of the second reactant was added to the first aqueous solution at 60° C. and gently stirred for 36 hours to obtain a second aqueous solution including the cation of this embodiment. 1 M sodium hydroxide solution was added to adjust the pH value to 9, and the solution was fully dialyzed in a dialysis bag with a molecular weight cutoff of 200 Da, and dried to obtain the product, i.e., the salt of this embodiment.

[0177] Detection of products or intermediates

[0178] The hydrochloride salt of the first reactant in this example is white crystals with a yield of about 0.8 g and a yield of about 80%.

[0179] The salt yield in this example is about 0.6 g, and the yield is about 32%.

[0180] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0181] Example 4

[0182] The salt of Example 4 is specifically shown in formula (4). That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 Methyl, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0183]

[0184] Preparation method

[0185] The preparation method of the salt of this embodiment is as follows.

[0186] - The first reactant is 3-methyl-2,2′-bipyridine;

[0187] - the second reactant is 2,2′-bipyridine; and

[0188] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0189] At 4°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0190] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 2 g of the first salt of this example was added, and stirring was continued at 4° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0191] 1 g of the second reactant was added to the first aqueous solution at 4°C and gently stirred for 48 hours to obtain a second aqueous solution including the cation of this embodiment. 1 M sodium hydroxide solution was added to adjust the pH value to 9, and the solution was fully dialyzed in a dialysis bag with a molecular weight cutoff of 200 Da, and the product, i.e., the salt of this embodiment, was obtained by drying.

[0192] Detection of products or intermediates

[0193] The hydrochloride salt of the first reactant in this example is white crystals with a yield of about 0.8 g and a yield of about 80%.

[0194] The salt yield in this example is about 1.6 g, and the yield is about 64%.

[0195] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 21 H 19 N4) + m / z = 327.16.

[0196] Example 5

[0197] The salt of Example 5 is specifically shown in formula (5). That is, Z 7 For carbon, Z 8 For carbon, Z9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 Methyl, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0198]

[0199] Preparation method

[0200] The preparation method of the salt of this embodiment is as follows.

[0201] - The first reactant is 2,2′-bipyridine;

[0202] - the second reactant is 3-methyl-2,2′-bipyridine; and

[0203] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0204] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0205] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0206] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0207] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0208] Detection of products or intermediates

[0209] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 21 H 19 N4) + m / z = 327.16.

[0210] Example 6

[0211] The salt of Example 6 is specifically shown in formula (6). That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 Methyl, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0212]

[0213] Preparation method

[0214] The preparation method of the salt of this embodiment is as follows.

[0215] - The first reactant is 3-methyl-2,2′-bipyridine;

[0216] - the second reactant is 2,2′-bipyridine; and

[0217] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0218] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0219] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0220] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0221] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0222] Detection of products or intermediates

[0223] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 21 H 19 N4) + m / z = 327.16.

[0224] Example 7

[0225] The salt of Example 7 is specifically shown in formula (7). That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is methyl, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0226]

[0227] Preparation method

[0228] The preparation method of the salt of this embodiment is as follows.

[0229] - The first reactant is 2,2′-bipyridine;

[0230] - the second reactant is 3-methyl-2,2′-bipyridine; and

[0231] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0232] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0233] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0234] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0235] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0236] Detection of products or intermediates

[0237] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 21H 19 N4) + m / z = 327.16.

[0238] Example 8

[0239] The salt of Example 8 is specifically shown in formula (8). That is, Z 7 is carbon, z8 is carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydroxyl group, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0240]

[0241] Preparation method

[0242] The preparation method of the salt of this embodiment is as follows.

[0243] - The first reactant is 4-hydroxy-2,2′-bipyridine;

[0244] - the second reactant is 2,2′-bipyridine; and

[0245] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0246] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0247] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0248] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0249] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0250] Detection of products or intermediates

[0251] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4O) + m / z = 329.3.

[0252] Example 9

[0253] The salt of Example 9 is specifically shown in formula (9). That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, z 18 is carbon, and z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydroxyl group, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0254]

[0255] Preparation method

[0256] The preparation method of the salt of this embodiment is as follows.

[0257] - The first reactant is 2,2′-bipyridine;

[0258] - the second reactant is 4-hydroxy-2,2′-bipyridine; and

[0259] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0260] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0261] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0262] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0263] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0264] Detection of products or intermediates

[0265] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4O) + m / z = 329.3.

[0266] Example 10

[0267] The salt of Example 10 is specifically represented by formula (10). 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydroxyl group, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0268]

[0269] Preparation method

[0270] The preparation method of the salt of this embodiment is as follows.

[0271] - The first reactant is 4-hydroxy-2,2′-bipyridine;

[0272] - the second reactant is 2,2'-bipyridine; and

[0273] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0274] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0275] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0276] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0277] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0278] Detection of products or intermediates

[0279] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4O) + m / z = 329.3.

[0280] Embodiment 11

[0281] The salt of Example 11 is specifically represented by formula (11). 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydroxyl group, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0282]

[0283] Preparation method

[0284] The preparation method of the salt of this embodiment is as follows.

[0285] - The first reactant is 2,2′-bipyridine;

[0286] - the second reactant is 4-hydroxy-2,2'-bipyridine; and

[0287] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0288] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0289] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0290] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0291] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0292] Detection of products or intermediates

[0293] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4O) + m / z = 329.3.

[0294] Example 12

[0295] The salt of Example 12 is specifically shown in formula (12). That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 Methyl, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R16 is hydrogen, R 17 is hydroxyl group, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0296]

[0297] Preparation method

[0298] The preparation method of the salt of this embodiment is as follows.

[0299] - The first reactant is 3-methyl-2,2′-bipyridine;

[0300] - the second reactant is 4-hydroxy-2,2′-bipyridine; and

[0301] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0302] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0303] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0304] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0305] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0306] Detection of products or intermediates

[0307] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 21 H 19 N4O) + m / z = 343.3.

[0308] Example 13

[0309] The salt of Example 13 is specifically shown in formula (13). 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 Methyl, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 Methyl, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 Methyl, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 Methyl, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0310]

[0311] Preparation method

[0312] The preparation method of the salt of this embodiment is as follows.

[0313] - The first reactant is 4,4′-dimethyl-2,2′-bipyridine;

[0314] - the second reactant is 4,4'-dimethyl-2,2'-bipyridine; and

[0315] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0316] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0317] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0318] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0319] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0320] Detection of products or intermediates

[0321] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 24 H 25 N4) + m / z = 369.21.

[0322] Embodiment 14

[0323] The salt of Example 14 is specifically shown in formula (141. That is, Z 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 Chlorine, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 Chlorine, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 Chlorine, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 Chlorine, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0324]

[0325] Preparation method

[0326] The preparation method of the salt of this embodiment is as follows.

[0327] - The first reactant is 4,4′-dichloro-2,2′-bipyridine;

[0328] - the second reactant is 4,4'-dichloro-2,2'-bipyridine; and

[0329] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0330] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0331] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0332] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0333] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0334] Detection of products or intermediates

[0335] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 13 N4Cl4 ) +'s m / z = 448.99.

[0336] Embodiment 15

[0337] The salt of Example 15 is specifically represented by formula (15). 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is amino, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R6 is hydrogen, R 7 is amino, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is amino, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is amino, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0338]

[0339] Preparation method

[0340] The preparation method of the salt of this embodiment is as follows.

[0341] - The first reactant is 4,4′-diamino-2,2′-bipyridine;

[0342] - the second reactant is 4,4'-diamino-2,2'-bipyridine; and

[0343] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0344] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0345] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0346] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0347] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0348] Detection of products or intermediates

[0349] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 21 N8) + m / z = 373.19.

[0350] Example 16

[0351] The salt of Example 16 is specifically shown in formula (16). 7 For carbon, Z 8 Nitrogen, Z 9 For carbon, Z 17 For carbon, Z 18 is nitrogen, and Z 19 is carbon, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 Does not exist, R 9 is hydrogen, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 does not exist, and R 19 is hydrogen, k=1, and X is a hexafluorophosphate ion.

[0352]

[0353] Preparation method

[0354] The preparation method of the salt of this embodiment is as follows.

[0355] - The first reactant is 2,3′-bipyridine;

[0356] - the second reactant is 2,3′-bipyridine; and

[0357] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0358] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0359] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0360] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0361] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0362] Detection of products or intermediates

[0363] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0364] Embodiment 17

[0365] The salt of Example 17 is specifically represented by formula (17). 7 For carbon, Z 8 Nitrogen, Z 9 For carbon, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R does not exist 8 , R 9 is hydrogen, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0366]

[0367] Preparation method

[0368] The preparation method of the salt of this embodiment is as follows.

[0369] - The first reactant is 2,3′-bipyridine;

[0370] - the second reactant is 2,2′-bipyridine; and

[0371] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0372] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0373] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0374] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0375] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0376] Detection of products or intermediates

[0377] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0378] Embodiment 18

[0379] The salt of Example 18 is specifically represented by formula (18). 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 For carbon, Z 18 is nitrogen, and Z 19is carbon, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 does not exist, and R 19 is hydrogen, k=1, and X is a hexafluorophosphate ion.

[0380]

[0381] Preparation method

[0382] The preparation method of the salt of this embodiment is as follows.

[0383] - The first reactant is 2,2′-bipyridine;

[0384] - the second reactant is 2,3′-bipyridine; and

[0385] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0386] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0387] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0388] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0389] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0390] Detection of products or intermediates

[0391] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0392] Embodiment 19

[0393] The salt of Example 19 is specifically represented by formula (19). 7 For carbon, Z 8 For carbon, Z 9 Nitrogen, Z 17 Nitrogen, Z 18 is carbon, and Z 19 is carbon, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 is hydrogen, R 8 is hydrogen, R 9 Does not exist, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 Does not exist, R 18 is hydrogen, and R 19 is hydrogen, k=1, and X is a hexafluorophosphate ion.

[0394]

[0395] Preparation method

[0396] The preparation method of the salt of this embodiment is as follows.

[0397] - The first reactant is 2,2′-bipyridine;

[0398] - the second reactant is 2,4′-bipyridine; and

[0399] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0400] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0401] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0402] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0403] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0404] Detection of products or intermediates

[0405] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0406] Embodiment 20

[0407] The salt of Example 20 is specifically represented by formula (20). 7 Nitrogen, Z 8 For carbon, Z 9 For carbon, Z 17 Nitrogen, Z 18 is carbon, and Z 19 is carbon, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 Does not exist, R 8 is hydrogen, R 9 is hydrogen, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R16 is hydrogen, R 17 Does not exist, R 18 is hydrogen, and R 19 is hydrogen, k=1, and X is a hexafluorophosphate ion.

[0408]

[0409] Preparation method

[0410] The preparation method of the salt of this embodiment is as follows.

[0411] - The first reactant is 2,4′-bipyridine;

[0412] - the second reactant is 2,4′-bipyridine; and

[0413] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0414] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0415] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0416] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0417] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0418] Detection of products or intermediates

[0419] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0420] Embodiment 21

[0421] The salt of Example 21 is specifically represented by formula (21). 7 Nitrogen, Z 8 For carbon, Z 9 For carbon, Z 17 For carbon, Z 18 is carbon, and Z 19 is nitrogen, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen, R 6 is hydrogen, R 7 does not exist, R 8 is hydrogen, R 9 is hydrogen, R 11 is hydrogen, R 12 is hydrogen, R 13 is hydrogen, R 14 is hydrogen, R 15 is hydrogen, R 16 is hydrogen, R 17 is hydrogen, R 18 is hydrogen, and R 19 does not exist, and k=1, and X is a hexafluorophosphate ion.

[0422]

[0423] Preparation method

[0424] The preparation method of the salt of this embodiment is as follows.

[0425] - The first reactant is 2,4′-bipyridine;

[0426] - the second reactant is 2,2′-bipyridine; and

[0427] - The first salt is ammonium hexafluorophosphate, that is, the first anion is a hexafluorophosphate ion.

[0428] At 25°C, place 1g of the first reactant in 10mL of 2M hydrochloric acid and stir vigorously until completely dissolved. Heat to 85°C for 30 minutes and concentrate under reduced pressure to 2mL. After cooling, crystals precipitate. Wash the crystals with ethanol solution 3 times and dry to obtain the hydrochloride of the first reactant.

[0429] 0.8 g of the first reactant hydrochloride was placed in 10 mL of ultrapure water, and stirred vigorously until completely dissolved. 4 g of the first salt of this example was added, and stirring was continued at 25° C. for 6 hours to obtain a first aqueous solution including protonated first reactant hydrochloride cations and first anions.

[0430] 0.8 g of the second reactant was added to the first aqueous solution at 25° C. and gently stirred for 24 hours to obtain a second aqueous solution including the cation of this embodiment. The solution was fully dialyzed using a dialysis bag with a molecular weight cutoff of 200 Da and dried to obtain a first intermediate product.

[0431] The first intermediate product was dissolved in 10 mL of ultrapure water, and dilute ammonia water was added to adjust the pH value to 9 to precipitate a large amount of white precipitate. The precipitate was filtered and the filter cake was washed twice with water and dried to obtain the product, i.e., the salt of this example.

[0432] Detection of products or intermediates

[0433] The salt of this example is subjected to high-resolution mass spectrometry to obtain the cation of this example, (C 20 H 17 N4) + m / z = 313.15.

[0434] Testing of MIC, MBC and MFC

[0435] The antimicrobial activity of the compounds of the present application is detected by the minimum inhibitory concentration MIC (minimal inhibitory concentration) and the minimum bactericide concentration MBC (minimal bactericide concentration) or MFC (minimal fungicidal concentration).

[0436] Count various bacteria and fungi and evenly inoculate them in a 96-well plate, with about 100 bacteria or fungal cells per well. The culture medium uses 100 μL of complete nutrient SDA culture medium. If it is anaerobic bacteria, add 20 μL of paraffin oil to seal it. At the same time, different concentrations of the example salt solution are added to each well according to the group, so that the final concentration of each experimental group is 0.5 mg / mL, 1 mg / mL, 1.5 mg / mL, 2 mg / mL, 2.5 mg / mL, 3 mg / mL, 3.5 mg / mL, 4 mg / mL, 4.5 mg / mL, 5 mg / mL, 5.5 mg / mL, and 6 mg / mL.

[0437] After culturing for 12 hours, the absorbance at 600 nm was measured and the MIC was determined.

[0438] Then, 20 μL of bacterial solution was extracted from each well and added to a new 96-well plate, and 180 μL of complete nutrient SDA medium was added. The culture was continued for 12 hours, and the absorbance at a wavelength of 600 nm was detected for MBC or MFC determination.

[0439] The results of the bacteria group are shown in Table 1, and the results of the fungus group are shown in Table 2. It can be seen that the cations of the examples of the present application have low MIC and MBC for various Gram-positive bacteria and Gram-negative bacteria, that is, they have strong ability to inhibit bacteria; the cations of the examples of the present application have low MIC and MFC for various fungi, that is, they also have strong ability to inhibit fungi.

[0440] Table 1 Antibacterial test results of the compounds in the examples

[0441]

[0442] “-”: The experiment was not conducted.

[0443] Table 2 Antifungal test results of the compounds in the examples

[0444]

[0445] The above-mentioned implementation modes are only preferred implementation modes of the present application and cannot be used to limit the scope of protection of the present application. Any non-substantial changes and substitutions made by technicians in this field on the basis of the present application shall fall within the scope of protection required by the present application.

Claims

1. A non-covalent dimeric cation comprising or consisting of a structure of formula (A), a tautomer thereof, or a stereoisomer thereof, wherein is a non-covalent bond, in, The Z 7 , the Z 8 , and the Z 9 is composed of one nitrogen and two carbons, and said Z 17 , the Z 18 , and the Z 19 It is composed of one nitrogen and two carbons; The Z 7 When R is nitrogen 7 , the Z 8 When R is nitrogen 8 , the Z 9 When R is nitrogen 9 , the Z 17 When R is nitrogen 17 , the Z 18 When R is nitrogen 18 , and the Z 19 When R is nitrogen 19 does not exist; and The R 1 , the R 2 , the R 3 , the R 4 , the R 5 , the R 6 , the Z 7 When R is carbon 7 , the Z 8 When R is carbon 8 , the Z 9 When R is carbon 9 , the R 11 , the R 12 , the R 13 , the R 14 , the R 15 , the R 16 , the Z 17 When R is carbon 17 , the Z 18 When R is carbon 18 , and the Z 19 When R is carbon 19 , which are each independently selected from the group consisting of hydrogen, methyl, phenyl, cyano, hydroxyl, amino, nitro, and chlorine.

2. The cation according to claim 1, characterized in that The R 1 , the Z 8 When R is carbon 8 , the R 11 , and the Z 18 When R is carbon 18 , are each independently selected from the group consisting of hydrogen and methyl; The R 2 , the Z 7 When R is carbon 7 , the R 12 , and the Z 17 When R is carbon 17 , are each independently selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine; and The R 3 , the R 4 , the R 5 , the R 6 , the Z 9 When R is carbon 9 , the R 13 , the R 14 , the R 15 , the R 16 , and the Z 19 When R is carbon 19 , is hydrogen.

3. The cation according to claim 1 or 2, characterized in that The R 1 , the R 3 , the R 4 , the R 5 , the R 6 , the Z 8 When R is carbon 8 , the Z 9 When R is carbon 9 , the R 11 , the R 13 , the R 14 , the R 15 , the R 16 , the Z 18 When R is carbon 18 , and the Z 19 When R is carbon 19 , is hydrogen; and The R 2 , the Z 7 When R is carbon 7 , the R 12 , and the Z 17 When R is carbon 17 , are each independently selected from the group consisting of hydrogen, hydroxyl, amino, and chlorine, and at least one of them is selected from the group consisting of hydroxyl, amino, and chlorine.

4. The cation according to any one of claims 1 to 3, characterized in that The R 1 , the R 2 , the R 3 , the R 4 , the R 5 , the R 6 , the Z 7 When R is carbon 7 , the Z 8 When R is carbon 8 , the Z 9 When R is carbon 9 , the R 11 , the R 12 , the R 13 , the R 14 , the R 15 , the R 16 , the Z 17 When R is carbon 17 , the Z 18 When R is carbon 18 , and the Z 19 When R is carbon 19 , is hydrogen.

5. The cation according to any one of claims 1 to 4, characterized in that The Z 7 , the Z 8 , the Z 17 , and the Z 18 for carbon; The Z 9 and the Z 19 for nitrogen; The R 9 and the R 19 does not exist; and The R 1 , the R 2 , the R 3 , the R 4 , the R 5 , the R 6 , the R 7 , the R 8 , the R 11 , the R 12 , the R 13 , the R 14 , the R 15 , the R 16 , the R 17 , and the R 18 Each is independently selected from the group consisting of hydrogen, methyl, hydroxyl, amino, and chlorine.

6. A salt, characterized in that include: The cation according to any one of claims 1 to 5; and The first anion, The first anion includes at least one selected from the group consisting of fluoride ion, chloride ion, bromide ion, iodide ion, sulfide ion, nitrate ion, sulfate ion, sulfite ion, thiosulfate ion, persulfate ion, selenate ion, phosphate ion, carbonate ion, hexafluorophosphate ion, hexafluorosilicate ion, acetate ion, sulfonate ion, benzoate ion, and polyphosphate ion.

7. The salt according to claim 6, characterized in that The first anion includes at least one selected from the group consisting of hexafluorophosphate ions, hexafluorosilicate ions, chloride ions, and sulfate ions.

8. A method for preparing a cation according to any one of claims 1 to 5 or a salt according to claim 6 or 7, characterized in that: include: contacting the first reactant with a first acid to obtain a first acid salt of the first reactant; In a first acidic environment, contacting the first reactant, the first acid salt, with a first salt including a first anion to obtain a first solution including a protonated first reactant, the first acid salt cation, and the first anion; Under a second acidic environment, adding a second reactant to the first solution to obtain a second solution or a first intermediate product; as well as adding a first base to the second solution or contacting the first intermediate product, wherein the first reactant comprises a compound of formula (C), and the second reactant comprises a compound of formula (D), 9. The preparation method according to claim 8, characterized in that: The first acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, and hydroiodic acid; and The first salt consists of a first cation and the first anion, and the first cation is an ammonium ion; and / or The contacting of the first reactant with the first acid is at a first temperature, wherein the first temperature is 0° C. to 70° C.; The first reactant, the first acid salt, is contacted with the first salt at a second temperature, wherein the second temperature is 0° C. to 70° C.; and The adding of the second reactant to the first solution is at a third temperature, wherein the third temperature is 0° C. to 70° C.; and / or The molar ratio of the first reactant to the first acid is 1:2 to 1:10; The molar ratio of the first reactant first acid salt to the first salt is 1:2 to 1:10; and The molar ratio of the protonated first reactant cation to the second reactant is 1:1 to 1:2; and / or The first acidic environment has a pH value less than or equal to 6; and The second acidic environment has a pH value less than or equal to 6; and / or The first base includes at least one selected from the group consisting of aqueous ammonia, sodium hydroxide, potassium hydroxide, and triethanolamine; and The step of adding the first base to the second solution or contacting the first intermediate product is to adjust the pH value of the second solution or the solution including the first intermediate product to be above 8.

10. Use of the cation according to any one of claims 1 to 5, or the salt according to claim 6 or 7, or the cation or salt prepared by the method according to claim 8 or 9 in antimicrobial treatment or in the preparation of an antimicrobial agent; Optionally, the microorganism is a bacterium and / or a fungus; Optionally, the bacterium is selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Enterococcus faecalis, Streptococcus mutans, Streptococcus thermophilus, Streptococcus lactis, Streptococcus bovis, Corynebacterium diphtheriae, Listeria monocytogenes, Bacillus subtilis, Bacillus cereus, Clostridium perfringens, Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, and Pseudomonas fluorescens; Optionally, the fungus is selected from the group consisting of Cryptococcus neoformans, Candida albicans, Trichophyton rubrum, Malassezia sphaeroides, Malassezia furfur, Aspergillus flavus, and Aspergillus niger.

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