New Application of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide

Abstract

The present invention relates to the technical field of new uses of compounds, and more specifically, to a novel application of N-(2-(5-(1,2-dithiolane-3-yl)pentanamido)ethyl)nicotinamide. This drug has a favorable therapeutic effect on Alzheimer's disease, not only expanding the drug options for treating Alzheimer's disease but also further broadening the application range of N-(2-(5-(1,2-dithiolane-3-yl)pentanamido)ethyl)nicotinamide.

Description

Technical Field

[0001] The present invention relates to the technical field of new applications of compounds, and in particular to a new application of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide. Background Art

[0002] Alzheimer's disease (AD) is a common neurodegenerative disease, accounting for 60% of dementia patients. With the increasing trend of population aging, AD has become a research hotspot in the medical field both domestically and internationally in recent years. AD pathology mainly affects the hippocampus, amygdala, temporal cortex, and frontal cortex, and clinically manifests as progressive cognitive degeneration, including memory loss, slowed thinking, and decreased language and learning abilities. The occurrence of AD can seriously affect the patient's emotions and cognitive abilities, placing a heavy burden on families and society. Therefore, the prevention and treatment of AD has become a social issue that needs to be urgently addressed. However, the five anti-AD drugs currently recognized in clinical practice can only improve cognitive impairment, but cannot alleviate pathology or cure the disease. Therefore, the development of new AD treatment drugs is of great significance.

[0003] In view of this, the present invention is proposed. Summary of the Invention

[0004] The present invention aims to provide a new application of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide. The embodiments of the present invention provide a new application of the aforementioned drug, which has a favorable therapeutic effect on Alzheimer's disease. This not only expands the drug selection for treating Alzheimer's disease, but also further expands the application range of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide.

[0005] The present invention is achieved in that:

[0006] In a first aspect, the present invention provides use of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide in the preparation of a medicament for treating Alzheimer's disease.

[0007] In an optional embodiment, the drug is a ferroptosis inhibitor.

[0008] In an alternative embodiment, the drug is a drug for improving memory disorders.

[0009] In an optional embodiment, the drug is at least one of the following agents: (1) an inhibitor that reduces the number of Aβ amyloid plaques; (2) an inhibitor that reduces Aβ 1-42 Content of inhibitors.

[0010] In an optional embodiment, the drug is to reduce p-Tau in the hippocampus S396 and p-Tau T231 levels of inhibitors.

[0011] In an optional embodiment, the drug is at least one of the following agents: (1) a promoter that promotes the expression level of PSD95 protein; (2) a promoter that increases the density of dendritic spines of hippocampal neurons.

[0012] In a second aspect, the present invention provides the use of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide as a single active ingredient in the preparation of a drug for treating Alzheimer's disease.

[0013] In a third aspect, the present invention provides the use of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide in the preparation of a drug for improving memory impairment.

[0014] In a fourth aspect, the present invention provides the use of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide in the preparation of an inhibitor for inhibiting ferroptosis.

[0015] The present invention has the following beneficial effects: the compound N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide provided in the embodiments of the present invention has a good therapeutic effect on Alzheimer's disease, can improve patients' memory impairment and olfactory function, provides a wider range of drug options for treating Alzheimer's disease, and also expands the scope of use of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0017] Figure 1 The result diagram provided for Experimental Example 1 of the present invention;

[0018] Figure 2-Figure 5 This is a result diagram provided for Experimental Example 2 of the present invention. DETAILED DESCRIPTION

[0019] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be purchased commercially.

[0020] The present invention provides a novel application of the compound N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide. N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide (hereinafter also referred to as N2L) is a dimer compound of α-lipoic acid and nicotinic acid, and its structural formula is shown below:

[0021]

[0022] The specific application is the treatment of Alzheimer's disease, which can significantly improve patients' memory impairment.

[0023] Furthermore, the drug can inhibit cell ferroptosis and increase the size of mitochondria and the number of mitochondrial cristae in cells.

[0024] The drug can also reduce the number of Aβ amyloid plaques, Aβ 1-42 Content, p-Tau in hippocampus S396 , p-Tau T231 levels, and is a promoter that increases the expression level of PSD95 protein and the density of dendritic spines in hippocampal neurons.

[0025] The features and performance of the present invention are further described in detail below with reference to the embodiments.

[0026] The synthesis of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide is described in Documents 1 and 2 below.

[0027] Literature 1: A, Jiang Y, Jin M, Chen J, Yan J, Liu P, Yao M, Cai W, Pi R. Discovery of a novel niacin-lipoic acid dimer N2L attenuating atherosclerosis and dyslipidemia with non-flushing effects. Eur J Pharmacol.2020Feb5;868:172871.doi:10.1016 / j.ejphar.2019.172871.

[0028] Reference 2: Pi Rongbiao, Jiang Yiming, Chao Xiaojuan, Liu Peiqing, Huang Yan, Yao Meicun, He Xixin. Nicotinic acid derivatives, their preparation methods and pharmaceutical compositions. ZL201110430852.0.2011.12.19.

[0029] Experimental Example 1

[0030] N2L inhibits RSL3-induced ferroptosis in HT22 neuronal cells in vitro

[0031] Agents: N2L provided in Example 1, ferroptosis inducer RSL3, and lipoic acid (hereinafter referred to as LA);

[0032] Experimental methods:

[0033] (1)MTT test

[0034] HT22 cells were cultured in DMEM supplemented with 10% fetal bovine serum, 100 units / ml penicillin, and 100 micrograms / ml streptomycin at 37°C and 5% carbon dioxide. The cells were passaged every other day using trypsin digestion (0.25%). When the HT22 cell density reached 80%, the cells were collected by digestion and centrifugation. HT22 cells were seeded in a 96-well plate at a density of 50,000 / mL and cultured for 24 hours before administration. After the administration treatment, 10 μL of MTT (5 mg / mL) was added to each well and incubated at 37°C for 3-4 hours. The generated formazan crystals were dissolved using DMSO (100 μL per well). After the formazan crystals were fully dissolved, the absorbance was measured at 490 nm using a microplate reader (Bio-Tek, USA), and the relative cell viability was calculated.

[0035] (2) Transmission electron microscopy observation of mitochondrial morphology

[0036] HT22 cells were fixed after treatment with 2.5% glutaraldehyde and 1% osmium tetroxide at 4°C for 24 h and 1 h, respectively. The cells were then dehydrated for 15 min at a range of acetone concentrations (50%, 70%, 80%, 90%, and 100%) and embedded in resin. The samples were sectioned and double-stained with uranyl acetate and lead citrate, and representative images were obtained using a JEM-1400 electron microscope (JEOL Co., Ltd., Japan).

[0037] Data statistical analysis

[0038] Data were analyzed using GraphPad Prism 8.0 software. Unless otherwise indicated, data are presented as mean ± standard error (SEM). Multiple groups were compared using one-way ANOVA (Dunnet t-tests), and two groups were compared using independent sample t-tests. Statistically significant differences were considered to be P < 0.05.

[0039] Experimental results

[0040] It should be noted that CT in the results represents blank control.

[0041] (1) N2L protects HT22 cells from RSL3-induced toxicity and mitochondrial shrinkage

[0042] See the results Figure 1 , among which, #P<0.05 and ##P<0.01*P<0.05, **P<0.01 and ***P<0.001 compared with RSL3 group.

[0043] Figure 1 The results of B are as follows: HT22 cells were exposed to different concentrations of RSL3 (0, 0.01μM, 0.03μM, 0.1μM, 0.3μM, 1μM, 3μM and 10μM) for 24h, and cell viability was detected using the MTT method. Figure 1 As shown in Figure A, RSL3 has a significant effect on HT22 cell viability starting from 0.1 μM, so 0.1 μM was selected as the modeling concentration.

[0044] Figure 1 The results in C and D are as follows: HT22 cells were treated with N2L (0.3 μM, 1 μM, 3 μM and 10 μM) and LA (0.3 μM, 1 μM, 3 μM and 10 μM) for 2 h, and then incubated with or without 0.1 μM RSL3 for 24 h. Cell viability was measured using MTT, and morphological changes were observed using a phase contrast microscope (scale bar). Figure 1 As shown in Figures C and D, N2L reduced RSL3-induced cytotoxicity in a dose-dependent manner and had a neuroprotective effect.

[0045] Figure 1 The results in Figure E are: Transmission electron micrographs of the perinuclear region and mitochondria of HT22 cells in the control group (denoted as CT), RSL3, and RSL3+N2L groups (scale bars = μm and 200 nm). The results are expressed as percentages of the values ​​in the untreated control group (mean ± SEM; n = 3-5). Figure 1 As shown in Figure E, the mitochondria of HT22 cells treated with RSL3 were shrunken and the number of cristae was reduced. After pretreatment with N2L, the mitochondrial morphology was significantly improved.

[0046] In summary, the above results indicate that N2L is an effective ferroptosis inhibitor.

[0047] Experimental Example 2

[0048] Experiment on the anti-fAD effect of N2L in APP / PS1 mice

[0049] Experimental methods

[0050] The experimental groups are shown in the table below.

[0051] Table 1. Experimental animal groups

[0052]

[0053] (1) New object recognition experiment

[0054] The novel object recognition test measures recognition memory in mice and is believed to be independent of the hippocampus, involving the medial prefrontal cortex and amygdala. The novel object recognition test consists of three phases: acclimation, familiarization, and testing. During the acclimation phase, each mouse freely explores the experimental box without the object. Subsequently, the mouse is removed from the experimental box and returned to its home cage. During the familiarization phase, two identical objects are placed in the experimental box, and the mouse is allowed to acclimate for 3 to 4 minutes. The objects are identical in color, texture, and shape. After each animal's experiment, the box is cleaned by spraying it with 70% ethanol. During the familiarization and testing phases, the objects are located on either side of the center of the box, equidistant from the walls. Each mouse is placed equidistant from the centerline of the box. Testing is conducted 24 hours after the familiarization phase, a test of long-term memory. The mouse is placed in the box, and object A is replaced with a novel object B. The mouse is allowed to freely explore both objects for 5 minutes. Recognition is considered to occur when the mouse's nose comes within 2 cm of the object, and the software calculates the exploration time of each mouse for objects A and B. Discrimination index = NF / N + F (where N is the time spent exploring the novel object and F is the time spent exploring the familiar object), expressed as a percentage.

[0055] (2) Open field test

[0056] The open field test is a method to evaluate the autonomous behavior, exploratory behavior and tension of experimental animals in a novel environment. The open field box (40cm×40cm×40cm) is an open box without a lid. Before the experiment, the mice were transferred to the laboratory for 2 hours of adaptation, and kept quiet and with stable light to allow them to adapt to the room environment. After the experiment began, each mouse was gently placed in the center of the open field box in turn and allowed to move freely for 5 minutes. The experimenter stayed away from the open field and kept the environment quiet. The movement of the mice (total distance traveled by the animal within 5 minutes, center activity distance, center activity time) and movement speed were recorded and analyzed. To avoid affecting the other mice, the tested mice were temporarily placed in a new cage. After a group of experiments was completed, all the mice were returned to their original cages. After each round of testing, the open box was wiped with 70% alcohol to remove the influence of the mouse odor, and the next round of experiments was carried out after the open box was dry.

[0057] (3) Enzyme-linked immunosorbent assay

[0058] For the hippocampus and cortex tissues of mice, 5 mice were selected from each group for homogenization, and then the Aβ1-42 content was measured according to the instructions of the commercial enzyme-linked immunosorbent assay kit. After mincing, the brain tissue was added to 100 mg of tissue in 1 mL of 1× PBS for homogenization and ultrasonic disruption. The tissue homogenate was centrifuged at 12,000×g at 4°C for 10 minutes, and the cells were lysed after repeated freeze-thaw twice to obtain the supernatant. During the test, the sample was dissolved in the standard diluent in the kit according to the instructions. Preliminary experiments were carried out to explore the optimal dilution ratio, and then batch testing was carried out. The cortex was diluted 50 times for the experiment, and the hippocampus was diluted 100 times for the experiment.

[0059] (4) Immunoblotting

[0060] For hippocampal tissue, five mice were selected per group. After anesthesia with 1% sodium pentobarbital (40 mg / kg), the mice were cervically dislocated. The brain tissue was separated from the skull using scissors, and the cerebral cortex and hippocampus were quickly separated on ice. Lysis buffer (10 mg:100 μL) was added at a weight:volume ratio of 1:10, along with equal proportions of protease and phosphatase inhibitors. The tissue was homogenized on ice for six consecutive 3-second intervals. If tissue fragments remained at the bottom of the EP tube, sonication was continued. After lysis on ice for 30 minutes, the cells were centrifuged at 12,000 g for 15 minutes at 4°C, and the supernatant was aspirated into another EP tube. Protein content was determined by the BCA assay according to the kit instructions. A 15 μg sample was loaded for each group. Based on the quantitative results, the volume of each tube was filled up with PBS. The sample was then mixed with 5× loading buffer at a ratio of 4:1. The protein was boiled for 5 minutes and centrifuged briefly before use. Electrophoresis: 12% separating gel, 5% stacking gel, and electrophoresis buffer were prepared according to the recipes. After securing the glass plate, place it in the electrophoresis tank. Remove the comb and load the sample. Run at 70V until the sample reaches the separating gel (approximately 30 minutes). Then, switch to 120V and stop electrophoresis when the bromophenol blue reaches the bottom. Prepare electrotransfer buffer and activate a PVDF membrane of appropriate size by soaking it in methanol. Gently pry the gel up and place it on filter paper. Cover the membrane with the gel and roll out any air bubbles. Secure it with a sponge pad and a mesh plate and insert it into the electrotransfer tank. Electrotransfer at 200mA constant current in an ice bath for 80 minutes. After electrotransfer, remove the membrane and wash it three times with 1× TBST for 5 minutes each. Then, immerse the membrane in blocking buffer containing 5% BSA and block at room temperature for 1.5 hours. Cut the membrane according to protein molecular weight and incubate it with diluted primary antibody overnight at 4°C. Then, incubate with secondary antibody and develop the color using ultrasensitive ECL chemiluminescent solution (Millipore, Germany). The images were exposed using a Tanon-5200 chemiluminescence imaging system (Tanon, China), and the developed bands were photographed by a CCD camera. The optical density of the images was analyzed using ImageJ.

[0061] (4) Golgi staining

[0062] Soak the brain tissue in a mixture of solution AB for 14 days (the solution contains 2.5g potassium dichromate, 2.5g mercuric chloride, and 2g potassium chromate, with a total volume of 240mL). On the 14th day, transfer the brain tissue to an appropriate amount of solution C and soak for 3-7 days. After soaking, perform frozen sections and embed them in TMF at a thickness of 120μm. Transfer the sections to anti-shedding slides. Rinse the sections twice with double-distilled water, each for 4 minutes. Soak the sections in a colorimetric solution consisting of 1 part solution D, 1 part solution E, and 2 parts double-distilled water for 10 minutes. Rinse the sections twice with double-distilled water, each for 4 minutes. Then, dehydrate the sections in a gradient of 50%, 75%, and 95% ethanol, each for 4 minutes. Dehydrate the sections in anhydrous ethanol four times, each for 4 minutes. Clear the sections in xylene three times, each for 4 minutes. Finally, mount the sections with a resin mounting medium and observe under an oil immersion lens.

[0063] Experimental results

[0064] It should be noted that: Note: D, DON = Donepezil group; N2L-L / H = N2L low / high dose group; D+N2L-L / H = Donepezil combined with N2L low / high dose group.

[0065] (1) N2L or donepezil alone or in combination improves memory impairment in APP / PS1 mice

[0066] (i) N2L or donepezil alone or in combination improves spatial learning and memory in APP / PS1 mice

[0067] Results see Figure 2 , among which, #P<0.05, ##P<0.001 compared with WT, *P<0.05 compared with APP / PS1. The details are as follows:

[0068] Figure 2 The results in Figure E show the swimming trajectories of eight groups of mice during the probe test. The circle in the upper left quadrant indicates the location of the hidden platform, and the curves represent the different swimming strategies of the mice.

[0069] Figure 2 The results in Figure B show the average escape latency of mice in six groups (WT, APP / PS1, DON, D+N2L-L, D+N2 LH, LA) in the hidden platform test performed on 5 consecutive days.

[0070] Figure 2 The results in Figure D show the platform crossing time of the six groups of mice in the probe test. Data are presented as mean ± SEM and analyzed using two-way ANOVA and Tukey's post hoc test (n = 8-9).

[0071] In the training experiment, it was found that ( Figure 2 Middle A), WT mice had the best learning and memory ability, and the time to find the platform (latency) shortened with the training time (from 30s to 15s); the APP / PS1 group had the worst learning ability, and the latency did not improve significantly during the 5-day training (from 55s to 40s); the latency of each drug treatment group gradually shortened during the 5-day training. Among them, the latency of the positive drug DON group on the 1st and 2nd days was statistically different from that of the APP / PS1 group (P<0.05, P<0.05). The latency of the N2L-H group gradually shortened, and on the 5th day, there was a significant difference in latency between the N2L-L and LA groups and the APP / PS1 model group (P<0.05); in comparison, the latency of the N2L-L and LA groups did not change significantly with that of the APP / PS1 model group ( Figure 2 A and B). In the space exploration experiment on the 6th day, we removed the escape platform. The swimming paths of the mice in each group in the space exploration experiment showed that the mice in the WT group had formed a memory of the location of the platform through training, and their swimming trajectories were relatively concentrated in the target quadrant. The swimming trajectories of the mice in the APP / PS1 group were aimless and distributed in other quadrants. At the same time, the number of times the mice in the APP / PS1 group crossed the platform decreased significantly. Compared with the APP / PS1 group, the DON group, N2L-L / H and LA groups recovered in the number of times they crossed the platform, and the difference in the N2L-H group was statistically significant (P<0.05) ( Figure 2 C and D).

[0072] (2) N2L improves olfactory impairment in APP / PS1

[0073] See the results Figure 3 APP / PS1 mice exhibit olfactory impairment in the buried food tray test (BFPT). Latency in the BFPT for six mouse groups (WT, APP / PS1, DON, N2L-L, N2L-H, LA). Data are shown as mean ± SEM, n = 7-10. *P < 0.05 compared with APP / PS1 model mice, P < 0.001 compared with WT.

[0074] The results showed that WT mice were faster at locating the buried food pellets, and their latency decreased daily, while the latency of the APP / PS1 group remained unchanged. Following treatment, starting from the second day of the experiment, the latency of each treatment group decreased to varying degrees. On the third day of the experiment, the latency of the N2L-H group decreased significantly compared to the APP / PS1 group (P < 0.05). The latency of the other treatment groups showed no statistically significant difference compared to the APP / PS1 group. This suggests that N2L alone can improve olfactory impairment in APP / PS1 mice.

[0075] (3) N2L improves Aβ and Tau pathology in APP / PS1 mice

[0076] See the results Figure 4 , ***P<0.001, **P<0.01, *P<0.05 compared with the APP / PS1 mouse group, ***P<0.001 compared with WT.

[0077] Figure 4 The results in panel A show: representative brain sections stained with antibodies against Aβ. Scale bar = 100 μm.

[0078] Figure 4 Results in panel B show quantification of amyloid plaques in the frontal cortex and hippocampus.

[0079] Figure 4 The results in Figures C and D show the concentrations of Aβ1-42 in the hippocampus and cortex of 9-month-old mice.

[0080] Figure 4 Results in Figure E: Western blot analysis and quantification of hippocampal APP and p-Tau231 / 396 levels. Data are presented as mean ± SEM and analyzed using one-way ANOVA with Tukey's post hoc test. Each dot represents a single mouse, with n = 5 mice per group, except for the LA group.

[0081] The above results showed that the number of plaques in the hippocampus and cortex of APP / PS1 mice was significantly increased compared with WT mice (P<0.001). The number of amyloid plaques in the cortex and hippocampus of DON mice was not significantly different from that of APP / PS1 group. N2L-L / H and LA treatment could significantly reduce Aβ plaques in the hippocampus (P<0.05, P<0.01, P<0.05) and cortex (P<0.01, P<0.001, P<0.001) of APP / PS1 mice. Among them, N2L-H (150 mg / kg) had an effect similar to that of LA (100 mg / kg) of approximately the same amount of substance, and reduced more plaques in the cortex than LA ( Figure 4 A and B). At the same time, Aβ1-42 levels in the cortex of APP / PS1 mice increased significantly (P<0.05). N2L could reduce the concentration of Aβ1-42, but the difference was not statistically significant. WB results showed that both N2L-H and LA could reduce the levels of APP and p-Tau231 / 396 in the hippocampus of APP / PS1 mice ( Figure 4 Middle C to E), improving Tau hyperphosphorylation pathology.

[0082] (6) N2L alleviates synaptic damage in APP / PS1 mice

[0083] Results see Figure 5 , among which, *P<0.05 compared with APP / PS1, #P<0.05 compared with WT.

[0084] The details are as follows:

[0085] Figure 5 Results in A and B represent Golgi-Cox staining of dendritic spines in six groups of DG neurons. Photos were taken with a 100X phase contrast microscope. Scale bar: 10 μm.

[0086] Figure 5 Results in C and D show Western blot and quantification of hippocampal PSD95, SV2a, and SYN1 levels in six groups (WT, APP / PS1, DON, N2L-L, N2L-H, LA). Data are presented as mean ± SEM and analyzed using one-way ANOVA followed by Tukey's post hoc test. n = 3-5 mice per group.

[0087] Golgi-Cox staining results showed that ( Figure 5 In Figures A and B), N2L-H and LA significantly restored the number of dendritic spines in APP / PS1 mice (P<0.01, P<0.05). The results of synaptic-related proteins showed that the expression level of PSD95 in APP / PS1 mice was decreased (P<0.05), while N2L-H and LA restored the expression of PSD95 protein (P<0.01, P<0.05) and increased the expression level of SYN-1 protein ( Figure 5 C and D).

Claims

1. Use of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide in the preparation of a drug for treating Alzheimer's disease.

2. The use according to claim 1, characterized in that The drug is a ferroptosis inhibitor.

3. The use according to claim 1, characterized in that The medicine is a medicine for improving memory impairment.

4. The use according to claim 1, characterized in that The Alzheimer's disease includes sporadic Alzheimer's disease and familial Alzheimer's disease.

5. The use according to claim 1, characterized in that The drug is at least one of the following agents: (1) an inhibitor that reduces the number of Aβ amyloid plaques; (2) an inhibitor that reduces the number of Aβ amyloid plaques; 1-42 Content of inhibitors.

6. The use according to claim 1, characterized in that The drug is used to reduce p-Tau in the hippocampus S396 and p-Tau T231 levels of inhibitors.

7. The use according to claim 1, characterized in that The drug is at least one of the following agents: (1) a promoter that promotes the expression level of PSD95 protein; (2) a promoter that increases the density of dendritic spines of hippocampal neurons.

8. Use of N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide as a single active ingredient in the preparation of a drug for treating Alzheimer's disease.

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