Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Chemistry, College of Natural Sciences, Sangmyung University, Hong-ji moon 2-gil 20, Jongno-gu, Seoul 110-743, Republic of Korea.
Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Biological Chemistry, Korea University of Science and Technology, Yuseong-Gu, Daejon 305-350, Republic of Korea.
Eur J Med Chem. 2015 Jun 5;97:245-58. doi: 10.1016/j.ejmech.2015.04.060. Epub 2015 Apr 30.
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.
代谢型谷氨酸受体 1（mGluR1）由于其在各种脑部疾病中的重要作用，一直是药物发现的主要靶点。最近的研究表明，mGluR1 与慢性疼痛有关，并且可以作为治疗神经性疼痛的有前途的靶标。为了开发新型的 mGluR1 拮抗剂，我们设计并合成了具有四氢噻吩并[2,3-c]吡啶骨架的化合物库。在这些化合物中，化合物 9b 和 10b 在体外表现出优异的拮抗活性，并在疼痛动物模型中表现出镇痛活性。这两种化合物均具有口服活性，化合物 9b 在大鼠中表现出良好的药代动力学特性。我们相信这些化合物可以提供有前途的先导化合物，适合用于治疗神经性疼痛。
