Kim, Jihye Cha, Eunji Park, Woo Kyu Lee, Hye Yeon Lim, Sang Min Kim, Hak Joong Pae, Ae Nim 2024-01-19T18:03:22Z 2024-01-19T18:03:22Z 2021-09-05 2020-02-15 0960-894X https://pubs.kist.re.kr/handle/201004/118950 Development of highly effective, safe, and fast-acting anti-depressants is urgently required for the treatment of major depressive disorder. It has been suggested that targeting 5-HT2A and 5-HT2C in addition to inhibition of serotonin reuptake may be beneficial in generating anti-depressant agents with better pharmacology and less adverse effects. We have developed phthalazinone-based compounds that potently bind to 5-HT2A, 5-HT2C, and the serotonin transporter. The representative compounds 11j and 11l displayed strong binding affinities against these targets, and showed favorable toxicity profiles as determined by hERG binding and CYP inhibition assays. Furthermore, these compounds presented promising anti-depressant effects comparable to fluoxetine and also synergistic effects with fluoxetine in forced swimming test, which implicates these compounds can be developed to help the treatment of major depressive disorder. English Pergamon Press Ltd. TRAZODONE Evaluation of anti-depressant effects of phthalazinone-based triple-acting small molecules against 5-HT2A, 5-HT2C, and the serotonin transporter Article 10.1016/j.bmcl.2019.126882 1 Bioorganic & Medicinal Chemistry Letters, v.30, no.4 Bioorganic & Medicinal Chemistry Letters 30 4 scie scopus 000507987200006 2-s2.0-85077164490 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article TRAZODONE Major depressive disorder Serotonin Selective serotonin reuptake inhibitor 5-HT2A 5-HT2C