{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:24:07Z","timestamp":1789079047730,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>A series of bis\u20103, 4\u2010dimethoxy\u2010fibrate derivatives was designed using structural simplification and bioisosteric principles. The hypolipidemic effects of these compounds were initially evaluated in a Triton WR 1339\u2010induced hyperlipidemic mouse model. The results indicated that compound T4 significantly reduced in levels of triglycerides (TG) and total cholesterol (TC). The dosage\u2010dependent results show that reductions in TG and TC are greater as the T4 dosage increases. In the high\u2010fat diet\u2010induced hyperlipidemia model, T4 was found to significantly lower TG, TC, and LDL\u2010C levels. Moreover, T4 exhibited hepatoprotective effects by substantially reducing levels of aspartate transaminase (AST) and alanine transaminase (ALT) in the liver. Histopathological examination indicated that T4 could inhibit hepatic lipid deposition and alleviate liver injury. Mechanistic investigations indicate that T4 upregulates hepatic peroxisome proliferator\u2010activated receptor\u2010alpha (PPAR\u2010\u03b1) protein expression, contributing to its lipid\u2010lowering effects. Molecular docking research has indicated a strong affinity between T4 and the active site of PPAR\u2010\u03b1. Furthermore, T4 has demonstrated antioxidant and anti\u2010inflammatory properties. These results suggest T4 could function as both an effective lipid\u2010lowering compound and a potential hepatoprotective agent.<\/jats:p>","DOI":"10.1002\/ddr.70271","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:07:39Z","timestamp":1774926459000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design and Synthesis of Bis\u20103,4\u2010Dimethoxybenzene\u2010Fibrate Derivatives as Potential Lipid\u2010Lowering and Hepatoprotective Agents Based on the Principles of Structural Simplification and Bioisosterism"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7550-4862","authenticated-orcid":false,"given":"Ling","family":"Ding","sequence":"first","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010Xianyang New Economic Zone  Shaanxi Province People's Republic of 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