Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain

作者：Nam Mina; Kim TaeHun; Kwak Jinsook; Seo Seon Hee; Ko Min Kyung; Lim Eun Jeong; Min Sun Joon; Cho Yong Seo; Keum Gyochang; Baek Du Jong; Lee Jiyoun^*; Pae Ae Nim

来源：European Journal of Medicinal Chemistry, 2015, 97: 245-258.

DOI：10.1016/j.ejmech.2015.04.060

• mGluR1 antagonist
• Metabotropic glutamate receptor
• Neuropathic pain
• Thiophene derivatives

Metabotropic glutamate receptor 1 (mGluR1) has been a prime target for drug discovery due to its heavy involvement in various brain disorders. Recent studies suggested that mGluR1 is associated with chronic pain and can serve as a promising target for the treatment of neuropathic pain. In an effort to develop a novel mGluR1 antagonist, we designed and synthesized a library of compounds with tetrahydrothieno [2,3-c]pyridine scaffold. Among these compounds, compound 9b and 10b showed excellent antagonistic activity in vitro and demonstrated pain-suppressing activity in animal models of pain. Both compounds were orally active, and compound 9b exhibited a favorable pharmacokinetic profile in rats. We believe that these compounds can provide a promising lead compound that is suitable for the potential treatment of neuropathic pain.

• 出版日期2015-6-5