Compound for preventing and / or treating ocular diseases, pharmaceutical composition and application thereof

Abstract

The present invention provides a compound for preventing or treating ocular diseases, a pharmaceutical composition, and an application thereof. The compound provided by the present invention is effective in controlling ametropia and axial length elongation, has a good safety profile, with no duration of use restrictions, and is capable of meeting the usage needs of adolescents with myopia.

Description

Compounds, pharmaceutical compositions and their uses for the prevention or treatment of eye diseases

[0001] This application claims priority to the following two earlier applications: Patent Application No. 202410985297.5, filed with the China National Intellectual Property Administration on July 22, 2024, entitled "Compounds, Pharmaceutical Compositions and Uses Thereof for the Prevention or Treatment of Eye Diseases"; and Patent Application No. 202510161612.7, filed with the China National Intellectual Property Administration on February 13, 2025, also entitled "Compounds, Pharmaceutical Compositions and Uses Thereof for the Prevention or Treatment of Eye Diseases". The entire contents of the aforementioned earlier applications are incorporated herein by reference. Technical Field

[0002] This invention belongs to the field of pharmaceuticals, specifically relating to a class of compounds, pharmaceutical compositions and their uses for the prevention or treatment of eye diseases. Background Technology

[0003] There are approximately 2.5 billion people with myopia worldwide, with a higher proportion in East Asians than in Europeans and Americans. In China, the incidence of myopia is as high as 48.5%, affecting as many as 700 million people, with a myopia rate of 52.7% among teenagers. The molecular mechanisms underlying the onset or worsening of myopia have not yet been fully elucidated. Although it can be corrected with glasses or contact lenses, there is currently no cure.

[0004] Myopia is caused by the focal point falling in front of the retina, making it difficult to see objects clearly. It can be broadly divided into two types: 1) Refractive myopia, caused by an excessively high refractive index of the cornea and lens. In refractive myopia, the lens, acting as a lens, cannot adjust its thickness correctly, resulting in focusing in front of the retina; 2) Axial myopia, caused by an excessively long axial length of the eyeball. Even with sufficient lens thinning, axial myopia still focuses in front of the retina. Most myopic patients have axial myopia, which worsens to high myopia. The increased elongation of the axial length stretches the retina and choroid backward, leading to various abnormalities in the fundus. This pathological myopia is one of the main causes of blindness.

[0005] It has been reported that atropine, a non-selective muscarinic antagonist, is effective as a topical 1% eye drop in the treatment of myopia (Chua et al., Ophthalmology, Dec 2006; 113(12):2285-91). In 2022, the Eye Centre of the Chinese University of Hong Kong conducted a two-year clinical trial on the prevention and treatment of myopia with low-concentration atropine in 474 Asian children. Clinical trial data showed that atropine at concentrations of 0.05% and 0.01% had good control effects on axial length and refractive error compared to the placebo group. The treatment effect of high concentration (such as 0.05% atropine) was better than that of low concentration (such as 0.01% atropine), but rebound was easy after discontinuation of the drug. The main side effects were photophobia, mydriasis, and myopic blurred vision caused by cycloplegia (inability to adapt). The incidence of photophobia side effect of low concentration atropine (0.01%) was as high as about 20%.

[0006] In 2024, China approved Xingqi Eye Hospital's low-concentration atropine sulfate (0.01%) for the purpose of slowing the progression of myopia in children and adolescents. Due to the aforementioned side effects of atropine, it is usually prescribed for nighttime use to avoid interfering with daytime work and study; therefore, there is an urgent need to develop a convenient drug for the prevention and treatment of myopia that does not cause photophobia or blurred vision. Summary of the Invention

[0007] To address the aforementioned technical problems, the present invention provides the following compounds, their racemates, stereoisomers, or pharmaceutically acceptable salts thereof:

[0008] According to some implementation schemes, the compound is

[0009] According to some implementation schemes, the pharmaceutically acceptable salt is an alkali metal salt, an alkaline earth metal salt, an addition salt of an amine or a basic amino acid.

[0010] According to some embodiments, the pharmaceutically acceptable salt is a sodium or potassium salt. Preferably, the compound is...

[0011] The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of at least one of the above-described compounds, their racemic mixtures, stereoisomers, or pharmaceutically acceptable salts thereof.

[0012] According to some embodiments, the pharmaceutical composition further includes one or more pharmaceutically acceptable excipients.

[0013] According to some embodiments, the pharmaceutical composition may further contain one or more additional therapeutic agents.

[0014] The present invention also provides another pharmaceutical composition comprising a therapeutically effective amount of at least one of the compound represented by formula (I), its racemate, stereoisomer, or pharmaceutically acceptable salt thereof;

[0015] in,

[0016] R1 and R2 may be the same or different, and each is independently selected from H and C. 1-3 Alkyl, C 1-3 Alkoxy or halogen.

[0017] According to some embodiments, the compound shown in formula (I) is a compound of formula (Ia) or formula (Ib):

[0018] The definitions of R1 and R2 are as described above.

[0019] According to some implementation schemes, the pharmaceutically acceptable salt is a sodium salt;

[0020] According to some implementation schemes, the compound shown in formula (I) is the same as the compound of formula (II):

[0021] According to some embodiments, the compound represented by formula (I) is a compound of formula (IIA) or formula (IIB):

[0022] According to some implementation schemes, R1 and R2 may be the same or different, and each is independently selected from H, methoxy, fluorine, chlorine or bromine.

[0023] According to some implementation schemes, R1 is selected from H, methoxy, or fluorine.

[0024] According to some implementation schemes, R2 is selected from H or methyl.

[0025] According to some embodiments, the content of the compound of formula (I) is about 1% to 99% based on the weight of the pharmaceutical composition.

[0026] According to some embodiments, the pharmaceutical composition further includes one or more pharmaceutically acceptable excipients.

[0027] According to some embodiments, the pharmaceutical composition further contains one or more additional therapeutic agents.

[0028] According to some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, such as at least one selected from self-solvents, suspending agents, emulsifiers, and antibacterial agents.

[0029] The present invention also provides a method for treating or preventing eye diseases or conditions, comprising administering to a patient a preventive or therapeutically effective amount of at least one of the above-mentioned compounds, their racemates, stereoisomers, or pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof.

[0030] The present invention also provides the use of at least one of the above-mentioned compounds, their racemates, stereoisomers, or pharmaceutically acceptable salts thereof in the preparation of medicaments for the treatment or prevention of eye diseases or conditions.

[0031] According to some embodiments, the compound is a compound of the following formula or a salt thereof;

[0032] According to some implementation schemes, the pharmaceutically acceptable salt is an alkali metal salt, an alkaline earth metal salt, or an addition salt of an amine or a basic amino acid;

[0033] According to some implementation schemes, the pharmaceutically acceptable salt is a sodium salt or a potassium salt;

[0034] Preferably, the compound is

[0035] According to some implementation schemes, the eye diseases or conditions mentioned are: myopia, dry eye syndrome, glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataracts, ocular tumors, and ocular surface diseases.

[0036] According to some implementation schemes, the eye disease or condition is myopia.

[0037] According to some implementation schemes, the myopia is pseudomyopia or transient myopia induced by close work.

[0038] According to some implementation schemes, the myopia is refractive myopia.

[0039] According to some implementation schemes, the myopia is axial myopia.

[0040] According to some implementation schemes, the myopia is in the prodromal stage of myopia, which refers to the stage where the child's hyperopia reserve is lower than the lower limit of the normal age range, that is, the stage of insufficient hyperopia reserve.

[0041] According to some implementation schemes, the myopia is in the myopia development stage, which refers to the stage where the child's myopia progresses by more than 50 degrees per year, but has not yet developed into high myopia. Beneficial effects

[0042] The compound provided by this invention has a good effect on controlling refractive errors and axial elongation, while also having good safety and no time limit for use, which can meet the needs of adolescents with myopia.

[0043] Terminology Definitions and Explanations

[0044] Unless otherwise stated, the definitions of groups and terms recorded in this application specification and claims, including definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, and definitions of specific compounds in the examples, can be arbitrarily combined and combined with each other. Such combinations and combinations of group definitions and compound structures should be understood as being within the scope of this application specification and / or claims.

[0045] The term “optional” (or “optionally”, “optionally”) in the general formula definition of this application means the case of being substituted by zero or one or more substituents. For example, “optionally substituted by one, two or more R” means that it may not be substituted by R (no substitution) or may be substituted by one, two or more R.

[0046] "More than" means three or more, such as 3, 4, 5, 6, 7, 8, 9 or 10.

[0047] Unless otherwise stated, the numerical ranges described in this specification and claims are equivalent to describing at least each specific integer value therein. For example, the numerical range "1-12" is equivalent to describing each integer value in the numerical range "1-12", namely 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.

[0048] Unless otherwise stated, heterocyclic, hypocyclic, heteroaryl, or hypoaryl includes all possible isomers, such as their positional isomers. Thus, for some illustrative, non-limiting examples, it may include forms in which one, two, or more of the following positions (if present) are substituted or bonded to other groups, including pyridin-2-yl, pyridin-2-yl, pyridin-3-yl, pyridin-3-yl, pyridin-4-yl, and pyridin-4-yl; thiophene or thiophene includes thiophene-2-yl, thiophene-2-yl, thiophene-3-yl, and thiophene-3-yl; pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, and pyrazol-5-yl.

[0049] The compounds disclosed herein may exist in various tautomer forms, and all such forms are included within the scope of this disclosure. The terms "tautomer" or "tautomer form" refer to a structural isomer that exists in equilibrium and readily transforms from one isomer to another. This includes all possible tautomers, i.e., existing as a single isomer or as a mixture of said tautomers in any proportion. Non-limiting examples include: keto-enols, imine-enamines, lactam-lactamimides, etc.

[0050] In the chemical structure of the compound described in this invention, the bond... This indicates that no configuration has been specified. Indicates absolute configuration, that is, if stereoisomers exist in the chemical structure, the bonds... It can be Or simultaneously include Two configurations.

[0051] In this invention, the compounds involved also include isotopically labeled compounds, which are the same as those shown in Formula I, but in which one or more atoms are replaced by atoms with atomic masses or mass numbers different from those normally found in nature. Examples of isotopes that can be incorporated into the compounds of this invention include isotopes of H, C, N, O, S, F, and Cl, respectively such as 2 H, 3 H, 13 C 11 C 14 C 15 N、 18 O、 17 O、 32 P, 35 S, 18 F and 36 Cl. Compounds of the present invention, their prodrugs, or pharmaceutically acceptable salts of said compounds or prodrugs containing the aforementioned isotopes and / or other isotopes are within the scope of the present invention. Certain isotopically labeled compounds of the present invention, such as those doped with radioactive isotopes (e.g.,... 3 H and 14 Compounds in (C) can be used for drug and / or substrate tissue distribution assays. Tritium (i.e., 3 H) and carbon-14 (i.e. 14 C) Isotopes are particularly preferred due to their ease of preparation and detectability. Furthermore, heavier isotopes (such as deuterium, i.e., 2H or D substitutions can provide certain therapeutic advantages derived from greater metabolic stability (e.g., increased in vivo half-life or reduced dose requirements) and are therefore preferred in some cases. The presence of hydrogen in the substituents of this invention, without the separate mention of the terms deuterium or tritium, does not imply the exclusion of deuterium or tritium, but rather may also include deuterium or tritium.

[0052] Those skilled in the art will understand that compounds can exist in the form of various pharmaceutically acceptable salts. If these compounds have a basic center, they can form acid addition salts; if these compounds have an acidic center, they can form base addition salts; and if these compounds contain both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), they can also form internal salts.

[0053] The compounds of the present invention may exist as solvates (such as hydrates), wherein the compounds of the present invention contain a polar solvent, particularly, for example, water, methanol, or ethanol, as a structural element of the lattice of the compound. The amount of the polar solvent, particularly water, may be stoichiometric or non-stoichiometric.

[0054] Depending on their molecular structure, the compounds of the present invention can be chiral, and therefore may exist in various enantiomeric forms. Thus, these compounds can exist in racemic or optically active forms. The compounds of the present invention encompass isomers of each chiral carbon in the R or S configuration, or mixtures thereof, and racemates. The compounds of the present invention or their intermediates can be isolated as enantiomeric compounds by chemical or physical methods known to those skilled in the art, or used in this form for synthesis. In the case of racemic amines, diastereomers are obtained from the mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as tartaric acid in both R and S forms, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (e.g., N-benzoylproline or N-benzenesulfonylproline), or various optically active camphorsulfonic acids. Chromatographic enantiomeric separation can also be advantageously performed using optically active resolving agents (e.g., dinitrobenzoylphenylglycine immobilized on silica gel, cellulose triacetate or other carbohydrate derivatives, or chiral derivatized isobutylene ester polymers). Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, such as hexane / isopropanol / acetonitrile.

[0055] The corresponding stable isomers can be separated using known methods, such as extraction, filtration, or column chromatography.

[0056] The term "patient" refers to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates, with humans being the most preferred.

[0057] The term “therapeutic effective amount” refers to the amount of an active compound or drug that researchers, veterinarians, physicians, or other clinicians are searching for in tissues, systems, animals, individuals, or humans to elicit a biological or medical response. It includes one or more of the following: (1) prevention of disease: e.g., prevention of disease, disorder, or condition in individuals susceptible to disease, disorder, or symptom but not yet experiencing or exhibiting the pathology or symptoms of the disease; (2) suppression of disease: e.g., suppression of disease, disorder, or symptom in individuals experiencing or exhibiting the pathology or symptoms of the disease, disorder, or symptom (i.e., prevention of further development of the pathology and / or symptoms); (3) relief of disease: e.g., relief of disease, disorder, or symptom in individuals experiencing or exhibiting the pathology or symptoms of the disease, disorder, or symptom (i.e., reversal of the pathology and / or symptoms). Attached Figure Description

[0058] Figure 1: Line graph of the change in right eye refractive power after drug administration in each group of animals in Test Example 1 (D, Mean±SEM).

[0059] Figure 2: Line graph of changes in axial length of the right eye after drug administration in each group of animals in Test Example 1 (mm, Mean±SEM).

[0060] Figure 3: Changes in body weight (g, Mean±SEM) of animals in each group after drug administration in Test Example 1. Detailed Implementation

[0061] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0062] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0063] The structures of the compounds of this invention were determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer with deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), or deuterated chloroform (CDCl3) as the solvent, and tetramethylsilane (TMS) as the internal standard.

[0064] LC-MS was performed using an Agilent 1200 Infinity Series mass spectrometer. HPLC was performed using an Agilent 1200DAD high-performance liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-performance liquid chromatograph (Gimini C18 150×4.6 mm column).

[0065] Thin-layer chromatography (TLC) uses Yantai Huanghai HSGF254 or Qingdao Haiyang Chemical GF254 silica gel plates. The standard size for TLC is 0.15mm to 0.20mm, while the standard size for TLC separation and purification is 0.4mm to 0.5mm. Column chromatography generally uses Yantai Huanghai 200-300 mesh silica gel as the carrier.

[0066] Unless otherwise specified, all reactions in this invention are carried out under continuous magnetic stirring, in a dry nitrogen or argon atmosphere, using a dry solvent, and the reaction temperature is expressed in degrees Celsius.

[0067] Example 1

[0068] A solution of sodium hydroxide (511.57 mg, 12.789 mmol) in water (1.7 mL) was added to a solution of 2-benzyloxyacetic acid Cpd-23 (commercially available) (2100 mg, 12.789 mmol) in acetonitrile (17 mL), and the mixture was stirred at room temperature for 1 hour. A large amount of product precipitated from the reaction solution. The product was filtered, and the filter cake was washed three times with acetonitrile. The filter cake was then lyophilized to obtain sodium 2-benzyloxyacetate Cpd-23A (2.21 g), yield: 92%.

[0069] 1 H NMR (400MHz, MeOD) δ7.40–7.36(m,2H),7.35–7.29(m,2H),7.28–7.23(m,1H),4.57(s,2H),3.85(s,2H).

[0070] Example 2

[0071] first step

[0072] (4-Fluorophenyl)methanol Cpd-06a (3 g, 0.0237 mol) was dissolved in anhydrous tetrahydrofuran (20 mL), cooled to 0 °C in an ice bath, and then sodium hydride (2.85 g, 0.1185 mol) was slowly added with stirring for 0.5 hours. Bromoacetic acid (2.64 g, 0.01896 mol) was then slowly added, and the mixture was brought back to room temperature. The reaction was continued with stirring for 16 hours. After the reaction was complete, water was added to quench the reaction, followed by extraction with ethyl acetate. The aqueous phase was adjusted to pH 3 with hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain 2-((4-fluorobenzyl)oxy)acetic acid Cpd-06 (2.5 g, colorless oil). MS m / z (ESI): 207.1 (M+Na).

[0073] Step 2

[0074] 2-((4-fluorobenzyl)oxy)acetic acid Cpd-06 (2.5 g, 0.021 mol) was dissolved in acetonitrile (30 mL), and sodium hydroxide aqueous solution (8 M, 2.97 mL) was added dropwise. The mixture was stirred at room temperature for 1 hour. A large amount of product precipitated from the reaction solution. The mixture was filtered, and the filter cake was washed three times with acetonitrile. The filter cake was lyophilized to obtain sodium 2-((4-fluorobenzyl)oxy)acetic acid Cpd-06A (2.72 g). Yield: 63.59%. MS m / z (ESI): 207.1 (M+Na).

[0075] 1 H NMR (400MHz, DMSO) δ7.43–7.25(m,2H),7.14(t,J=8.8Hz,2H),4.47(s,2H),3.55(s,2H).

[0076] Sodium salt compounds, as shown in Table 1 below, were prepared using conditions similar to those in the examples described above. The structural characterization data of these compounds are listed in Table 1.

[0077] Table 1

[0078] Biological evaluation

[0079] Test Example 1

[0080] 1.1 Experimental Objective: To evaluate the preventive and therapeutic effects of the compounds disclosed in this invention on the eyes using a form deprivation myopia (FDM) model in myopic guinea pigs.

[0081] 1.2 Experimental Methods: Sixty healthy male spotted guinea pigs were selected, and 26 animals were randomly divided into three groups based on the axial length and refractive power of their right eyes: normal control group, model control group, and experimental group. The normal control group consisted of 6 animals, and the other two groups each contained 10 animals. Starting on day 1, the right eyes of animals in groups 2 and 3 underwent FDM modeling for 4 weeks. The right eyes of animals in groups 2 and 3 were administered phosphate-buffered saline (PBS) and the compound of this invention (2%) (eye drops, once daily, 20 μL / eye) daily.

[0082] During the experiment, animals underwent routine clinical observation daily and were weighed weekly. Refractive error and axial length were measured in the right eye of each group of animals before modeling, on days 14 and 28. Refractive error and axial length were measured in the left eye of each group of animals on day 29. All surviving animals were euthanized at the end of the experiment.

[0083] 1.3 Experimental Results

[0084] The results of refractive error and axial length measurements of the right eye of each group of animals are shown in Tables 2 and 3.

[0085] Table 2. Refractive index data of animals in each group (D, Mean±SEM)

[0086] Note: Compared with the normal control group at the same time period. a This means P ≤ 0.05. aa This means P ≤ 0.01. aaa This indicates that P ≤ 0.001; compared with the control group of the same period, b This means P ≤ 0.05. bb This means P ≤ 0.01. bbb This means P ≤ 0.001.

[0087] Table 3. Axial length data of animals in each group (mm, Mean±SEM)

[0088] Note: Compared with the normal control group at the same time period. a This means P ≤ 0.05. aa This means P ≤ 0.01. aaa This indicates that P ≤ 0.001; compared with the control group of the same period, b This means P ≤ 0.05. bb This means P ≤ 0.01. bbb This indicates that P ≤ 0.001. Experimental conclusion:

[0089] Under the experimental conditions, the model group data showed that form deprivation successfully induced a myopia model in FDM guinea pigs. The compound of the present invention, when administered continuously as eye drops (once a day, 20 μL / eye) for 28 days, could slow down the decrease in refractive power in FDM model guinea pigs, and the compound of the present invention had a good control effect on the decrease in refractive power (as shown in Table 2 and Figure 1). Continuous eye drops for 28 days could significantly slow down the axial elongation of FDM model guinea pigs, and the compound of the present invention had a good control effect on the axial elongation (as shown in Table 3 and Figure 2). The trend of weight change in guinea pigs after continuous administration of the compound of the present invention for 28 days was consistent with that of the normal group (as shown in Figure 3). There was no weight loss or other adverse reactions in the guinea pigs, indicating that the compound of the present invention has good safety.

[0090] Test Example 2

[0091] 2.1 Experimental Objective: To evaluate the preventive and therapeutic effects of the compounds disclosed in this invention on the eyes using a form deprivation myopia (FDM) model in myopic guinea pigs.

[0092] 2.2 Experimental Methods: Sixty healthy male spotted guinea pigs were selected, and 35 animals were randomly divided into 5 groups based on the axial length and refractive power of their right eyes: normal control group, model control group, experimental group 1, experimental group 2, and experimental group 3. The normal control group consisted of 3 animals, the model group consisted of 8 animals, and each experimental group consisted of 8 animals. Starting on day 1, the right eyes of the model and experimental groups underwent FDM modeling for 4 weeks. The right eyes of the model group animals were given phosphate-buffered saline (PBS) solution (20 μL / eye, once daily) daily, while the right eyes of the experimental group animals were given the compound of this invention (2%) (20 μL / eye, once daily).

[0093] During the experiment, animals underwent routine clinical observation daily and were weighed weekly. Refractive error and axial length were measured in the right eye of each group of animals before modeling, on day 14, and day 28. All surviving animals were euthanized at the end of the experiment.

[0094] 2.3 Experimental Results

[0095] The results of refractive error and axial length measurements of the right eye of each group of animals are shown in Tables 4 and 5.

[0096] Table 4. Refractive index data of animals in each group (D, Mean±SEM)

[0097] Note: Compared with the normal control group at the same time period. a This means P ≤ 0.05. aa This means P ≤ 0.01. aaa This indicates that P ≤ 0.001; compared with the control group of the same period, b This means P ≤ 0.05. bbThis means P ≤ 0.01. bbb This means P ≤ 0.001.

[0098] Table 5. Axial length data of animals in each group (mm, Mean±SEM)

[0099] Note: Compared with the normal control group at the same time period. a This means P ≤ 0.05. aa This means P ≤ 0.01. aaa This indicates that P ≤ 0.001; compared with the control group of the same period, b This means P ≤ 0.05. bb This means P ≤ 0.01. bbb This means P ≤ 0.001.

[0100] Experimental conclusion:

[0101] Under the conditions of this experiment, the model group data showed that form deprivation successfully induced the FDM guinea pig myopia model. The compound of the present invention could slow down the decrease in refractive power of FDM model guinea pigs after continuous eye drops (1 time / day, 20 μL / eye) for 28 days. The compound of the present invention has a good control effect on the decrease in refractive power (as shown in Table 4). Continuous eye drops for 28 days could significantly slow down the axial elongation of FDM model guinea pigs. The compound of the present invention has a good control effect on the axial elongation (as shown in Table 5).

[0102] The embodiments of the technical solution of the present invention have been described above by way of example. It should be understood that the protection scope of the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made by those skilled in the art within the spirit and principles of the present invention should be included within the protection scope of the claims of this application.

Claims

1. A compound as described below, racemate, stereoisomer thereof, or a pharmaceutically acceptable salt thereof: Preferably, the compound is Preferably, the pharmaceutically acceptable salt is an alkali metal salt, an alkaline earth metal salt, an amine or a basic amino acid addition salt; Preferably, the pharmaceutically acceptable salt is a sodium salt or a potassium salt; Preferably, the compound is 2. A pharmaceutical composition comprising a therapeutically effective amount of at least one of the compound of claim 1, a racemate, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof; Preferably, the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients; Preferably, the pharmaceutical composition further comprises one or more additional therapeutic agents.

3. A method for treating or preventing an ocular disease or disorder, comprising administering to a patient a prophylactically or therapeutically effective amount of at least one of the compound of claim 1, a racemate, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 2; Preferably, the compound is a compound described by the following formula or a salt thereof; Preferably, the pharmaceutically acceptable salt is an alkali metal salt, an alkaline earth metal salt, an amine or a basic amino acid addition salt; Preferably, the pharmaceutically acceptable salt is a sodium salt or a potassium salt; Preferably, the compound is Preferably, the ocular disease or disorder is myopia, dry eye, glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataract, ocular tumor, ocular surface disease; Preferably, the ocular disease or disorder is myopia; Preferably, the myopia is pseudomyopia or short-distance work-induced transient myopia; Preferably, the myopia is refractive myopia; Preferably, the myopia is axial myopia; Preferably, the myopia is in the pre-mycopic stage, which refers to a stage in which the hyperopia reserve of children has fallen below the lower limit of the normal age range, i.e., a stage of insufficient hyperopia reserve; Preferably, the myopia is in the myopic development stage, which refers to a stage in which the myopic progression speed of children exceeds 50 degrees per year, but has not yet developed into high myopia.

4. Use of at least one of the compound of claim 1, a racemate, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 2 in the manufacture of a medicament for treating or preventing an ocular disease or disorder; Preferably, the compound is a compound described by the following formula or a salt thereof; Preferably, the pharmaceutically acceptable salt is an alkali metal salt, an alkaline earth metal salt, an amine or a basic amino acid addition salt; Preferably, the pharmaceutically acceptable salt is a sodium salt or a potassium salt; Preferably, the compound is Preferably, the ocular disease or disorder is myopia, dry eye, glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataract, ocular tumor, ocular surface disease; Preferably, the ocular disease or disorder is myopia; Preferably, the myopia is pseudomyopia or short-distance work-induced transient myopia; Preferably, the myopia is refractive myopia; Preferably, the myopia is axial myopia; Preferably, the myopia is in the pre-mycopic stage, which refers to a stage in which the hyperopia reserve of children has fallen below the lower limit of the normal age range, i.e., a stage of insufficient hyperopia reserve; Preferably, the myopia is in the myopic development stage, which refers to a stage in which the myopic progression speed of children exceeds 50 degrees per year, but has not yet developed into high myopia.

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