ATAD2 has received attention as one of the potential oncogene with tumor-promoting aspects in many malignancies. ATAD2 is a highly conserved bromodomain family protein that exerts its biological functions by mainly AAA ATPase and bromodomain. Several small molecule inhibitors have been described in the literature. AZ13824374 ( recently reported by Holt and co-workers showed promising in vitro (bio-chemical, cellular) and antiproliferative activity in range of breast cancer models. In this work, we described scalable synthetic route for triazolopyridazine derivative (, a key intermediate of AZ13824374 ( without using CO in the process. Triazolopyridazine helps to attain the bioactive conformation for AZ13824374 ( through its crucial interaction with Tyr 1021 of ATAD2. Additionally, triazolopyridazine is extensively used as an intermediate for anticancer agents. This encouraged us to develop cost-effective and scalable process for it.

中文翻译：

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抗癌剂药效团的替代合成路线：三唑并哒嗪衍生物


ATAD2 作为在许多恶性肿瘤中具有促癌作用的潜在癌基因之一而受到关注。 ATAD2是高度保守的bromodomain家族蛋白，主要通过AAA ATPase和bromodomain发挥其生物学功能。文献中已经描述了几种小分子抑制剂。 AZ13824374（Holt 及其同事最近报道，在一系列乳腺癌模型中显示出有前景的体外（生化、细胞）和抗增殖活性。在这项工作中，我们描述了三唑并哒嗪衍生物（AZ13824374 的关键中间体）的可扩展合成路线（在此过程中不使用 CO。三唑并哒嗪有助于获得 AZ13824374 的生物活性构象（通过其与 ATAD2 的 Tyr 1021 的关键相互作用）。此外，三唑并哒嗪被广泛用作抗癌药物的中间体。这鼓励我们开发具有成本效益和它的可扩展流程。