Yang, Ha Yun Tae, Jinsung Seo, Yong Wan Kim, Yoon Jung Im, Hye Yeon Choi, Gil Don Cho, Heeyeong Park, Woo-Kyu Kwon, Oh Seung Cho, Yong Seo Ko, Minkyung Jang, HyunSeo Lee, Jaeick Choi, Kihang Kim, Chan-Hwa Lee, Jiyoun Pae, Ae Nim 2024-01-20T12:31:19Z 2024-01-20T12:31:19Z 2021-09-05 2013-05 0223-5234 https://pubs.kist.re.kr/handle/201004/128092 Obesity is one of the most serious public health problems worldwide in the 21st century. Current therapeutic treatment for obesity is mostly focused on preventive measures involving dietary control and physical exercises in combination with anti-obesity medications. However, most of these anti-obesity medications have little or no effect on weight loss, and some cases have demonstrated fatal side effects. Due to the urgent need for highly potent and selective anti-obesity agents, the serotonin receptors (5-HTR) have been the focus of much interest as a novel therapeutic target. In this report, we have developed pyrimidoazepine analogs targeting the 5-HT2A and 5-HT2C receptors and evaluated their biological activity in vitro and in vivo as novel anti-obesity agents. We were able to identify 6p as the most potent 5-HT2A and 5-HT2C ligand in vitro (IC50 = 3 nM and 2.3 nM, respectively), and this compound also demonstrated the greatest potency in vivo. In an acute obesity model, mice treated with 6p showed significant decrease in body weight gain and food intake over approximately 77-94% compared to a control group. In a chronic obesity model, mice treated with 6p also showed a marked decrease in food intake and body weight gain. (C) 2013 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER Novel pyrimidoazepine analogs as serotonin 5-HT2A and 5-HT2C receptor ligands for the treatment of obesity Article 10.1016/j.ejmech.2013.02.020 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.63, pp.558 - 569 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 63 558 569 N scie scopus 000322855400053 2-s2.0-84875321161 Chemistry, Medicinal Pharmacology & Pharmacy Article ANTAGONIST AGONIST 5-HT2A antagonist 5-HT2C antagonist Obesity Pyrimidoazepine Serotonin receptor ligands