A novel series of benzodihydrofuran derivatives was developed as potent MEK inhibitors through scaffold hopping based on known clinical compounds. Further SAR exploration and optimization led to another benzofuran series with good oral bioavailability in rats. One of the compounds EBI-1051 (28d) demonstrated excellent in vivo efficacy in colo-205 tumor xenograft models in mouse and is suitable for pre-clinical development studies for the treatment of melanoma and MEK associated cancers. Compared to AZD6244, EBI-1051 showed superior potency in some cancer cell lines such as colon-205, A549 and MDA-MB-231.

中文翻译：

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EBI-1051的发现：具有苯并呋喃支架的新型，口服有效的MEK抑制剂

基于已知的临床化合物，通过支架跳跃，开发了一系列新的苯并二氢呋喃衍生物作为有效的MEK抑制剂。SAR的进一步探索和优化导致了另一种在大鼠中具有良好口服生物利用度的苯并呋喃系列。化合物EBI-1051（28d）在小鼠colo-205肿瘤异种移植模型中表现出出色的体内功效，适合用于治疗黑素瘤和与MEK相关的癌症的临床前研究。与AZD6244相比，EBI-1051在某些癌细胞系（例如结肠205，A549和MDA-MB-231）中显示出更高的效力。