CN116903489A - Terphenyl compound, preparation method and application thereof - Google Patents

Terphenyl compound, preparation method and application thereof Download PDF

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CN116903489A
CN116903489A CN202310865168.8A CN202310865168A CN116903489A CN 116903489 A CN116903489 A CN 116903489A CN 202310865168 A CN202310865168 A CN 202310865168A CN 116903489 A CN116903489 A CN 116903489A
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terphenyl compound
compound
terphenyl
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林德良
王淑容
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Beijing Handian Pharmaceutical Co ltd
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
    • C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/36—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
    • C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
    • C07C215/08—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with only one hydroxy group and one amino group bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
    • C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms

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Abstract

The invention relates to the technical field of medicines, in particular to a terphenyl compound, a preparation method and application thereof. Terphenyl compoundsComprising a compound of formula 1:wherein R is 1 Selected from H, R 2 Selected from halogen and C1-C6 alkyl; r is R 3 Selected from substituted secondary amine groups. The compound has good inhibition effect on PD-1/PD-1, can be used as a PD-1/PD-1 small molecule inhibitor, and then has the effect of treating tumors.

Description

Terphenyl compound, preparation method and application thereof
Technical Field
The invention relates to the technical field of medicines, in particular to a terphenyl compound, a preparation method and application thereof.
Background
Cancer immunotherapy has progressed rapidly in recent years. Immune checkpoint inhibitors targeting Programmed cell-death receptor1 (PD-1) and Programmed cell-death ligand 1 (PD-L1) have achieved significant success in clinical applications in the tumor field. In the tumor microenvironment, the combination of PD-1 in tumor infiltrating lymphocytes and PD-L1 expressed on the surfaces of tumor cells can make tumors generate immune escape and promote the growth of the tumors. Currently, 15 antibody drugs targeting PD-1/PD-L1 are approved by the U.S. Food and Drug Administration (FDA) and by the national drug administration to the market, which includes 9 PD-1 monoclonal antibodies and 6 PD-L1 monoclonal antibodies. However, the inherent limitations of antibody drugs include poor tissue and tumor permeability, long half-life, poor oral bioavailability, expensive production costs, and immunogenicity, which severely hampers the effectiveness of immunotherapy. The small molecule inhibitor taking PD-1/PD-L1 as a target spot has been attracting more and more attention because of better pharmacokinetic characteristics and oral availability, and can be combined with antibody drugs or even directly replace the antibody drugs.
However, the development of PD-1/PD-L1 small molecule inhibitors is far behind monoclonal antibodies, and only a few small molecule inhibitors have entered clinical studies. Early due to lack of structural information of targets, reasonable design of PD-1/PD-L1 small molecule inhibitors is limited. Until 2015, hPD-1, hPD-L1 crystal complex structures were published, more and more patents directed to antibodies, cyclic peptides and small molecule inhibitors of PD-1 and PD-L1 were published, of which the most attractive is a class of 2-methyl-3-biphenyl derivatives disclosed by Bai Shi Midshurica (BMS). The Hoalk subject group researches find that the compounds can induce PD-L1 proteins to polymerize, and two PD-L1 monomers can form a cylindrical hydrophobic pocket, so that an easy patent medicine target is provided for the design of small molecular medicines. Therefore, small molecule inhibitors targeting PD-L1 are a hotspot for research. However, no small molecule inhibitors targeting PD-L1 have been approved for sale to date, which also suggests that the development of novel PD-1/PD-1 small molecule inhibitors remains a laborious task and is a clinically unmet need.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to provide a terphenyl compound, a preparation method and application thereof. The terphenyl compound provided by the embodiment of the invention has good inhibition effect on PD-1/PD-1, can be used as a PD-1/PD-1 small molecule inhibitor, and further has the effect of treating tumors.
The invention is realized in the following way:
in a first aspect, the present invention provides a terphenyl compound comprising a compound of formula 1:formula 1, wherein R 1 Selected from H, R 2 Selected from halogen and C1-C6 alkyl; r is R 3 Selected from substituted secondary amine groups.
In an alternative embodiment, R 2 Selected from any one of F, cl, br, I and C1-C3 alkyl.
In an alternative embodiment, R 2 Selected from any one of Cl, br, methyl and ethyl.
In an alternative embodiment, the substituted secondary amine group is selected fromWherein n represents any integer of 1 to 5, R 4 Selected from hydroxyl, acetamido, and piperazinone groups.
In an alternative embodiment, the terphenyl compound is selected from any one of the compounds represented by the following structural formulas:
in a second aspect, the present invention provides a method for preparing a terphenyl compound according to the foregoing embodiment, including: the synthesis was performed with reference to the following synthesis route:
in an alternative embodiment, the method comprises: in the step a, the molar ratio of 1-bromo-3-iodo-2-methylbenzene to phenylboronic acid is 1:1-2, the adopted catalyst is a palladium catalyst, the temperature is 80-100 ℃, and the time is 8-12 hours;
the conditions of step b include: the catalyst is palladium catalyst, the temperature is 70-90 ℃ and the time is 10-16 hours;
the conditions of step c include: the catalyst is palladium catalyst, the temperature is 80-100 ℃ and the time is 8-12 hours;
the step d comprises the following steps: the temperature is 20-30 ℃ and the time is more than 12 hours.
In a third aspect, the present invention provides a PD-1/PD-L1 inhibitor, which comprises a terphenyl compound according to the previous embodiment, a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof.
In a fourth aspect, the present invention provides an application of the terphenyl compound, the pharmaceutically acceptable salt, the hydrate, the solvent compound or the prodrug thereof according to the previous embodiment in preparing a PD-1/PD-L1 inhibitor.
In a fifth aspect, the present invention provides an application of the terphenyl compound, the pharmaceutically acceptable salt, the hydrate, the solvent compound or the prodrug thereof in preparing an anti-tumor drug.
The invention has the following beneficial effects: the terphenyl compound provided by the embodiment of the invention has good inhibition effect on PD-1/PD-L1, can be used as a PD-1/PD-1 small molecule inhibitor, and further has the effect of treating tumors.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
The invention is trueEmbodiments provide terphenyl compounds including compounds of formula 1:formula 1, wherein R 1 Selected from H, R 2 Selected from halogen and C1-C6 alkyl; r is R 3 Selected from substituted secondary amine groups.
Specifically, R 2 Selected from any one of F, cl, br, I and C1-C3 alkyl. The C1-C6 alkyl group may be any of alkyl groups such as methyl, ethyl, n-propyl, isopropyl, tert-butyl, etc.
Substituted secondary amine groups selected fromWherein n represents any integer of 1 to 5, R 4 Selected from hydroxyl, acetamido, and piperazinone groups.
Specifically, the terphenyl compound is selected from any one of compounds shown in the following structural formulas:
further, the invention provides a preparation method of the terphenyl compound in the previous embodiment, which comprises the following steps: taking 1-bromo-3-iodo-2-methylbenzene and phenylboronic acid as starting materials, and carrying out 3-step Suzuki-Miyaura coupling reaction to obtain a key intermediate 4; intermediate 4 reacts with corresponding amine through Schiff base, and finally the target product is obtained through reduction.
The synthesis is carried out with specific reference to the following synthesis routes:
reagents and conditions in the synthetic route: (a) Phenylboronic acid, pd (PPh) 3 ) 4 Equal palladium catalyst, K 2 CO 3 Isocarbonates, organic solvents, such as toluene/water (v/v=2:1), nitrogen at 80-100 ℃,8-12h; (b) B (B) 2 Pin 2 ，PdCl 2 Palladium catalyst such as (dtbpf), CH 3 COOK, 70-90 ℃ under nitrogen, 10-16h; (c) Pd (PPh) 3 ) 4 Equal palladium catalyst, K 2 CO 3 Isocarbonates, organic solvents, such as toluene/water (V: v=2:1), nitrogen at 80-100 ℃,8-12h; (d) i-starting materials containing secondary amine groups, organic solvents, e.g. CH 2 Cl 2 /CH 3 OH (v/v=1:1), glacial acetic acid, room temperature, 2h; ii: boron-based substances such as NaCNBH 3 Overnight at normal temperature.
In a third aspect, the present invention provides a PD-1/PD-L1 inhibitor, which comprises a terphenyl compound according to the previous embodiment, a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof.
In a fourth aspect, the present invention provides an application of the terphenyl compound, the pharmaceutically acceptable salt, the hydrate, the solvent compound or the prodrug thereof according to the previous embodiment in preparing a PD-1/PD-L1 inhibitor.
In a fifth aspect, the present invention provides an application of the terphenyl compound, the pharmaceutically acceptable salt, the hydrate, the solvent compound or the prodrug thereof in preparing an anti-tumor drug.
The features and capabilities of the present invention are described in further detail below in connection with the examples.
Example 1
The embodiment of the invention provides a terphenyl compound, which has the following structural formula:
the embodiment also provides a synthesis method of the terphenyl compound, which comprises the following steps:
(1) Synthesis of 3-bromo-2-methyl-1, 1' -biphenyl
1-bromo-3-iodo-2-methylbenzene (1.18 g,4.0 mmol), phenylboronic acid (0.59 g,4.8 mmol) and tetrakis triphenylphosphine palladium (0.23 g,0.2 mmol) were dissolved in 30ml of a mixed solution of toluene and water (volume ratio 2:1), then potassium carbonate (1.1 g,8.0 mmol) was added to the mixture, reacted under nitrogen at 90℃for 9 hours,TLC detection reaction was complete. The reaction mixture was extracted three times with ethyl acetate (30 ml), and the organic phases were combined, washed 2 times with 5ml of water and 5ml of saturated brine, respectively, followed by anhydrous Na 2 SO 4 And (5) drying. After filtration, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to give 0.82g of a colorless liquid, yield 83.2%.
The product characterization data are as follows: 1 H NMR(400MHz，DMSO)δ7.86-7.61(m，3H)，7.48-7.37(m，4H)，7.21(t，J＝8.4Hz，1H)，2.31(s，3H)。
(2) Synthesis of 4, 5-tetramethyl-2- (2-methyl- [1,1' -biphenyl ] -3-yl) -1,3, 2-dioxaborane
3-bromo-2-methyl-1, 1 '-biphenyl (0.82 g,3.33 mmol), pinacol biborate (1.0 g,4.0 mmol) and 1,1' -bis (di-tert-butylphosphonate) ferrocene dichloropalladium (0.1 g,0.167 mmol) were dissolved in 15ml DMSO solution, followed by potassium acetate (0.962 g,9.8 mmol) and reacted at 80℃under nitrogen for 12h, TLC detection was complete. The reaction mixture was extracted three times with ethyl acetate (30 ml), and the organic phases were combined, washed twice with 5ml of water, 5ml of saturated brine, and then with anhydrous Na 2 SO 4 And (5) drying. After filtration, the solvent was removed under reduced pressure, and 0.645g of a colorless liquid was purified by silica gel column chromatography to obtain a residue, which was 66.5% in yield.
The product characterization data are as follows: 1 H NMR(400MHz，DMSO)δ7.92-7.60(m，4H)，7.49-7.45(m，3H)，7.15(dd，J＝7.4,1.7Hz，1H)，2.33(s，3H)，1.37(d，J＝8.0Hz，12H)。
(3) Synthesis of 3-chloro-2 '-methyl- [1,1':3', 1' -triphenyl ] -4-carbaldehyde
4, 5-tetramethyl-2- (2-methyl- [1,1' -biphenyl)]-3-yl) -1,3, 2-dioxaborane (0.645 g2.19 mmol), 4-bromo-2-chlorobenzaldehyde (0.41 g,1.9 mmol) and tetrakis triphenylphosphine palladium (0.11 g,0.095 mmol) were dissolved in 30ml toluene and water (volume ratio 2: 1) To the mixture was then added potassium carbonate (0.650 g,4.75 mmol) and the reaction was completed by TLC under nitrogen at 90℃for 12 h. The reaction mixture was extracted three times with ethyl acetate (30 ml), and the organic phases were combined, washed 2 times with 5ml of water and 5ml of saturated brine, respectively, followed byBy anhydrous Na 2 SO 4 And (5) drying. After filtration, the solvent was removed under reduced pressure to give a residue of 0.34g as a white solid purified by silica gel column chromatography in 58.5% yield.
The product characterization data are as follows: 1 H NMR(400MHz，DMSO)δ10.08(s，1H),8.46(d，J＝1.7Hz，1H)，7.98-7.60(m，4H),7.56-7.46(m，6H),2.31(s，3H)。
(4) Synthesis of N- (2- (((3-chloro-2 '-methyl- [1,1':3', 1' -triphenyl ] -4-yl) methyl) amino) ethyl) acetamide
3-chloro-2 '-methyl- [1,1':3', 1' -triphenyl ] -4-carbaldehyde (0.34 g,1.1 mmol), N-acetyl ethylenediamine (0.135 g,1.32 mmol) were dissolved in 10ml of a mixed solution of dichloromethane and methanol (volume ratio 1:1), followed by addition of 0.07ml of glacial acetic acid. After 2h at room temperature, sodium cyanoborohydride (0.242, 3.85 mmol) was added and the reaction was stirred overnight at room temperature, and the completion of the reaction was detected by TLC. The solvent was distilled off under reduced pressure, and the obtained residue was purified by a silica gel column to obtain 0.33g of a white solid, yield 76.6%.
The product characterization data are as follows: 1 H NMR(400MHz，DMSO)δ8.47(d，J＝1.8Hz，1H),7.71(d，J＝8.5Hz，2H)7.68-7.63(m，3H),7.52(t，J＝8.5Hz，1H)，7.49-7.45(m，3H),7.38(d，J＝8.4Hz，1H),4.06(s，2H)，3.48(t，J＝7.1Hz，2H)，2.82(t，J＝7.1Hz，2H)，2.23(s，3H)，1.86(s，3H)。
examples 2 to 6
The corresponding terphenyl compound was synthesized by the synthetic method of example 1, and the structure and characterization data of the prepared terphenyl compound were as follows:
example 2: 1 H NMR(400MHz，DMSO)δ8.21(d，J＝1.9Hz，1H),7.72(d，J＝8.5Hz，2H)7.68-7.63(m，3H),7.52(t，J＝8.5Hz，1H)，7.48-7.45(m，3H),7.36(d，J＝8..3Hz，1H),4.02(s，2H)，3.48(t，J＝7.1Hz，2H)，2.82(t，J＝7.1Hz，2H)，2.23(s，3H)，1.86(s，3H)。
example 3: 1 H NMR(400MHz，DMSO)δ8.47(d，J＝1.8Hz，1H),7.71(d，J＝8.5Hz，2H)7.64-7.61(m，3H),7.52(t，J＝8.5Hz，1H)，7.48-7.45(m，3H),7.38(d，J＝8..4Hz，1H),4.05(s，2H)，3.51(t，J＝6.7Hz，2H)，2.79(t，J＝6.7Hz，2H)，2.23(s，3H)。
example 4: 1 H NMR(400MHz，DMSO)δ8.21(d，J＝1.9Hz，1H),7.72-7.70(m，2H)7.65-7.61(m，3H),7.52(t，J＝8.5Hz，1H)，7.48-7.45(m，3H),7.36(d，J＝8.3Hz，1H),4.00(s，2H)，3.51(t，J＝6.7Hz，2H)，2.78(t，J＝6.7Hz，2H)，2.23(s，3H)。
example 5: 1 H NMR(400MHz，DMSO)δ8.47(d，J＝1.8Hz，1H),7.72-7.70(m，2H)7.65-7.61(m，3H),7.52(t，J＝8.5Hz，1H)，7.48-7.45(m，3H),7.38(d，J＝8.4Hz，1H),4.06(s，2H)，3.55(d，J＝15.8Hz，2H)，3.40-3.12(m，2H)，2.95-2.57(m，6H)，2.23(s，3H)。
example 6: 1 H NMR(400MHz，DMSO)δ8.21(d，J＝1.9Hz，1H),7.74-7.70(m，2H)7.65-7.61(m，3H),7.52(t，J＝8.5Hz，1H)，7.48-7.46(m，3H),7.36(d，J＝8.3Hz，1H),4.02(s，2H)，3.55(d，J＝15.8Hz，2H)，3.40-3.13(m，2H)，2.95-2.57(m，6H)，2.23(s，3H)。
detection example 1
Autodock Vina molecular docking experiments were performed on the following compounds, and the binding energy between the following compounds and PD-L1 proteins was examined, and the results are shown in Table 1.
TABLE 1
From Table 1, it is understood that the compounds of the examples of the present invention were modified to provide groups having reduced binding ability, which were unable to perform good binding, and thus were unable to effectively inhibit PD-1/PD-L1 binding.
Detection example 2
1. Test of Compounds for PD-1/PD-L1 inhibitory Activity
The in vivo antitumor activity of the partial compounds was tested using Homogeneous Time Resolved Fluorescence (HTRF) method. The terphenyl derivative provided by the embodiment of the invention is tested for the inhibition effect on PD-1/PD-L1 by using an HTRF PD-1/PD-L1binding assay kit kit developed by Cisbio company according to the operation of a specification.
The experimental process comprises the following steps: in 96-well plate, adding 2 μl of diluent or target compound diluted with diluent, adding 4 μl of PD-1 protein and 4 μl of PD-L1 protein, incubating at room temperature for 15min, and adding 10 μl of anti-Tag1-Eu 3+ And anti-Tag2-XL665, fluorescence signals at 665nm and 620nm were detected after incubation for 1h at room temperature. HRTR rate= (665 nm/620 nm) ×10 4 . Each compound was assayed at 8 concentrations of 3 secondary wells per concentration. Then calculate the inhibition rate and IC 50 Experimental data are shown in table 2.
Inhibitory Activity of the Compounds of Table 2 on PD-1/PD-L1
Compounds of formula (I) IC 50 (nM)
Example 1 7.3
Example 2 6.8
Example 3 15.4
Example 4 13.1
Example 5 4.5
Example 6 2.5
BMS202 24.3
According to Table 2, the inhibition effect of the terphenyl derivative provided by the embodiment of the invention on PD-1/PD-L1 is measured according to a standard operation procedure by adopting the HTRF technology, and the result shows that the terphenyl derivative provided by the embodiments 1-6 of the invention has an obvious inhibition effect on PD-1/PD-L1 by taking the compound BMS202 as a reference. The compounds provided by the embodiments of the present invention are useful for the treatment of immune-based disorders such as hepatitis, HIV and tumors.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A terphenyl compound characterized by comprising a compound represented by formula 1:
wherein R is 1 Selected from H, R 2 Selected from halogen and C1-C6 alkyl; r is R 3 Selected from substituted secondary amine groups.
2. The terphenyl compound of claim 1, wherein R 2 Selected from any one of F, cl, br, I and C1-C3 alkyl.
3. The terphenyl compound of claim 2, wherein R 2 Selected from any one of Cl, br, methyl and ethyl.
4. The terphenyl compound of claim 1, wherein the substituted secondary amine group is selected from the group consisting ofWherein n represents any integer of 1 to 5, R 4 Selected from hydroxyl, acetamido, and piperazinone groups.
5. The terphenyl compound according to claim 1, wherein the terphenyl compound is selected from any one of the compounds represented by the following structural formulas:
6. a method for preparing the terphenyl compound of claim 1, comprising: the synthesis was performed with reference to the following synthesis route:
7. the method of manufacturing according to claim 6, comprising: in the step a, the molar ratio of 1-bromo-3-iodo-2-methylbenzene to phenylboronic acid is 1:1-2, the adopted catalyst is a palladium catalyst, the temperature is 80-100 ℃, and the time is 8-12 hours;
the conditions of step b include: the catalyst is palladium catalyst, the temperature is 70-90 ℃ and the time is 10-16 hours;
the conditions of step c include: the catalyst is palladium catalyst, the temperature is 80-100 ℃ and the time is 8-12 hours;
the step d comprises the following steps: the temperature is 20-30 ℃ and the time is more than 12 hours.
8. A PD-1/PD-L1 inhibitor, comprising the terphenyl compound of claim 1, a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof.
9. Use of a terphenyl compound of claim 1, a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof, in the preparation of a PD-1/PD-L1 inhibitor.
10. Use of a terphenyl compound of claim 1, a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof, in the preparation of an anti-neoplastic drug.
CN202310865168.8A 2023-07-14 2023-07-14 Terphenyl compound, preparation method and application thereof Pending CN116903489A (en)

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