Novel pyrimidoazepine analogs as serotonin 5-HT2A and 5-HT 2C receptor ligands for the treatment of obesity

Ha Yun Yang, Jinsung Tae, Yong Wan Seo, Yoon Jung Kim, Hye Yeon Im, Gil Don Choi, Heeyeong Cho, Woo Kyu Park, Oh Seung Kwon, Yong Seo Cho, Minkyung Ko, Hyunseo Jang, Jaeick Lee, Kihang Choi, Chan Hwa Kim, Jiyoun Lee, Ae Nim Pae

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


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-HT 2C 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.

Original languageEnglish
Pages (from-to)558-569
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 2013

Bibliographical note

Funding Information:
This work was supported by Korea Institute of Science and Technology .

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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