A library of new 2-substituted pyrrolo[1,2-b]pyridazine derivatives were rapidly assembled and identified as PARP inhibitors. Structure-activity relationship for this class of inhibitor resulted in the discovery of most potent compounds 15a and 15b that exhibited about 29- and 5- fold selective activity against PARP-1 over PARP-2 respectively. The antiproliferative activity of the as-prepared compounds were demonstrated by further celluar assay in BRCA2-deficient V-C8 and BRCA1-deficient MDA-MB-436 cell lines, displaying that compound 15b could robustly reduce the corresponding cell proliferation and growth with CC₅₀s of 340 and 106 nM respectively. The PK property of 15b was also investigated here.

一个新的 2-取代吡咯并[1,2- b ]哒嗪衍生物文库被快速组装并鉴定为 PARP 抑制剂。这类抑制剂的构效关系导致发现了最有效的化合物15a和15b，它们对 PARP-1 的选择性活性分别是 PARP-2 的 29 和 5 倍。通过在 BRCA2 缺陷型 V-C8 和 BRCA1 缺陷型 MDA-MB-436 细胞系中的进一步细胞测定证明了所制备化合物的抗增殖活性，表明化合物15b可以用 CC ₅₀强力降低相应的细胞增殖和生长s 分别为 340 和 106 nM。15b的PK属性 这里也被调查了。