H3R antagonist 4 

H3R antagonist 4 (compound 11L) was a dual inhibitor of cholinesterase and histamine receptor (H3R), with corresponding IC₅₀ of 7.04 μM (eeAChE), 9.73 μM (hAChE)(reversible) and 1.09 nM (H3R) , respectively. H3R antagonist 4 inhibited the aggregation of Aβ_1-42 induced by itself and Cu²⁺ (95.48% and 88.63%) , and degraded the Aβ_1-42 fibrils induced by itself and Cu²⁺ (80.16% and 89.30%) . H3R antagonist 4 chelate biometals such as Cu²⁺, Zn²⁺, Al³⁺, and Fe²⁺. H3R antagonist 4 significantly reduced tau protein hyperphosphorylation induced by Aβ_1-42 and inhibited RSL-3-induced apoptosis and ferroptosis in PC12 cells. H3R antagonist 4 had the best blood-brain barrier permeability and intestinal absorption in hCMEC/D3 and hPepT1-MDCK cells.H3R antagonist 4 ameliorates learning and memory impairment in a mouse model of Alzheimer's disease induced by scopolamine (HY-N0296) ^[1] .

H3R antagonist 4 (compound 11l) inhibited eeAChE, eqBuChE and hAChE with IC₅₀ values of 7.04 μM, 13.40 μM and 9.73 μM, respectively^[1].
H3R antagonist 4 combines with AChE and occupies CAS, midgorge site and PAS. It interacts with the active site and peripheral anion site of hAChE, and can bind both CAS and PAS sites as two-site AChE inhibitors^[1].
H3R antagonist 4 inhibited the aggregation of Aβ_1-42 induced by itself and Cu²⁺ (95.48% and 88.63%, respectively)(ThT fluorescence assay) , and degraded the Aβ_1-42 fibrils induced by itself and Cu²⁺ (80.16% and 89.30% , respectively)(TEM) ^[1].
The IC₅₀ of H3R antagonist 4 (TRFRET) was 1.09 nM^[1].
H3R antagonist 4 (5 μM, 10 μM and 20 μM)(WB) inhibited abnormal tau phosphorylation in PC12 cells^[1].
H3R antagonist 4 (11 μM) increased the survival rate of PC12 (800 μM H₂O₂) to 75.66%, and decreased the level of ROS. PC12 cells were protected from H₂O₂ by decreasing ROS accumulation, and the percentage of apoptotic cells was significantly increased to 22.9% ± 0.36%^[1].
H3R antagonist 4 (5, 10, 20 μM) inhibited RSL3-induced iron death in PC12 cells and significantly increased cell viability. The induced injury increased the permeability of blood-brain barrier in vitro^[1].
H3R antagonist 4 (UV-vis spectrometry) can sequester Cu ²⁺, Zn ²⁺, Al ³⁺ and Fe ^{2+ [1]}.
H3R antagonist 4 increased PEPT1 protein expression in hPepT1-MDCK cells^[1].
H3R antagonist 4 (0-80 μM, 1h) showed anti-inflammatory effect in BV-2 cells and did not affect proliferation^[1] .

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

H3R antagonist 4 (compound 11l) (2.5 and 5.0 mg/kg) can effectively improve the pathological morphological changes of nerve cells induced by scopolamine（HY-N0296），and could significantly improve the cognitive deficit and spatial memory of AD model mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

568.61

C₃₀H₃₆N₂O₉

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• [1]. Jiao Chen,et al. Scutellarein derivatives with histamine H3 receptor antagonism and cholinesterase inhibitory potency as multi target-directed ligands for possible Alzheimer's disease therapy. Bioorganic Chemistry. 2024 Aug 8;151:107704.  [Content Brief]