Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors | |
Xiang, Hao-Yue1,2; Chen, Jian-Yang2; Huan, Xia-Juan2; Chen, Yi3; Gao, Zhao-bing4; Ding, Jian2; Miao, Ze-Hong2; Yang, Chun-Hao2 | |
刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS |
2021 | |
卷号 | 31页码:4 |
关键词 | Antiproliferative Cancer PARP inhibitors Pyrrolo[12-b]pyridazine |
ISSN号 | 0960-894X |
DOI | 10.1016/j.bmcl.2020.127710 |
通讯作者 | Miao, Ze-Hong(zhmiao@simm.ac.cn) ; Yang, Chun-Hao(chyang@simm.ac.cn) |
英文摘要 | 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 CC(50)s of 340 and 106 nM respectively. The PK property of 15b was also investigated here. |
资助项目 | Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120185003] ; State Key Laboratory of Drug Research Program[SIMM1903ZZ-03] |
WOS关键词 | POLY(ADP-RIBOSE) POLYMERASE-1 PARP-1 ; DESIGN ; DISCOVERY ; CANCER |
WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
语种 | 英语 |
出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
WOS记录号 | WOS:000602366100002 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/296377] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Miao, Ze-Hong; Yang, Chun-Hao |
作者单位 | 1.Cent South Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Medica, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Medica, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Medica, Key Lab Receptor Res, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Xiang, Hao-Yue,Chen, Jian-Yang,Huan, Xia-Juan,et al. Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2021,31:4. |
APA | Xiang, Hao-Yue.,Chen, Jian-Yang.,Huan, Xia-Juan.,Chen, Yi.,Gao, Zhao-bing.,...&Yang, Chun-Hao.(2021).Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,31,4. |
MLA | Xiang, Hao-Yue,et al."Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 31(2021):4. |
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