The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4. Optimization efforts were aided by X-ray crystal structures of inhibitors bound to IRAK4. Structure activity relationship (SAR) studies led to the identification of compound 29 which exhibited sub-micromolar potency in a LTA stimulated cellular assay.

中文翻译：

---

发现和基于结构的设计作为有效和选择性IRAK4抑制剂的4,6-二氨基烟酰胺

识别用于治疗自身免疫性疾病的IRAK4的小分子抑制剂一直是研究的热点。我们发现了有效抑制IRAK4的新型4，6-二氨基烟酰胺。与IRAK4结合的抑制剂的X射线晶体结构有助于优化工作。结构活性关系（SAR）研究导致鉴定了在LTA刺激的细胞分析中表现出亚微摩尔效价的化合物29。