ar-9281 has been researched along with Disease-Models--Animal* in 4 studies
4 other study(ies) available for ar-9281 and Disease-Models--Animal
| Article | Year |
|---|---|
Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors.
The soluble epoxide hydrolase (sEH) has been suggested as a pharmacological target for the treatment of several diseases, including pain-related disorders. Herein, we report further medicinal chemistry around new benzohomoadamantane-based sEH inhibitors (sEHI) in order to improve the drug metabolism and pharmacokinetics properties of a previous hit. After an extensive in vitro screening cascade, molecular modeling, and in vivo pharmacokinetics studies, two candidates were evaluated in vivo in a murine model of capsaicin-induced allodynia. The two compounds showed an anti-allodynic effect in a dose-dependent manner. Moreover, the most potent compound presented robust analgesic efficacy in the cyclophosphamide-induced murine model of cystitis, a well-established model of visceral pain. Overall, these results suggest painful bladder syndrome as a new possible indication for sEHI, opening a new range of applications for them in the visceral pain field. Topics: Analgesics; Animals; Capsaicin; Cyclophosphamide; Disease Models, Animal; Enzyme Inhibitors; Epoxide Hydrolases; Humans; Mice; Urea; Visceral Pain | 2022 |
Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis.
Topics: Animals; Binding Sites; Catalytic Domain; Disease Models, Animal; Drug Design; Enzyme Inhibitors; Epoxide Hydrolases; Female; Humans; Lipopolysaccharides; Male; Memantine; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Rats; Sepsis; Structure-Activity Relationship; Survival Rate; Urea | 2021 |
2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors:
Topics: Acute Disease; Animals; Binding Sites; Catalytic Domain; Cell Line; Cell Survival; Disease Models, Animal; Endoplasmic Reticulum Stress; Enzyme Inhibitors; Epoxide Hydrolases; Half-Life; Humans; Mice; Microsomes; Molecular Dynamics Simulation; Pancreatitis; Rats; Solubility; Structure-Activity Relationship; Urea | 2020 |
1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia.
1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea 14a (AR9281), a potent and selective soluble epoxide hydrolase inhibitor, was recently tested in a phase 2a clinical setting for its effectiveness in reducing blood pressure and improving insulin resistance in pre-diabetic patients. In a mouse model of diet induced obesity, AR9281 attenuated the enhanced glucose excursion following an intraperitoneal glucose tolerance test. AR9281 also attenuated the increase in blood pressure in angiotensin-II-induced hypertension in rats. These effects were dose-dependent and well correlated with inhibition of the sEH activity in whole blood, consistent with a role of sEH in the observed pharmacology in rodents. Topics: Adamantane; Administration, Oral; Angiotensin II; Animals; Antihypertensive Agents; Blood Glucose; Disease Models, Animal; Enzyme Inhibitors; Epoxide Hydrolases; Hypertension; Insulin Resistance; Mice; Obesity; Rats; Urea | 2011 |