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Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors

文献类型：期刊论文

作者Xiang, Hao-Yue2,3; Chen, Jian-Yang3; Huan, Xia-Juan3; Chen, Yi1; Gao, Zhao-bing4; Ding, Jian3; Miao, Ze-Hong3; Yang, Chun-Hao3
刊名BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
出版日期2021
卷号31页码:4
关键词Antiproliferative Cancer PARP inhibitors Pyrrolo[12-b]pyridazine
ISSN号0960-894X
DOI10.1016/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.
WOS关键词POLY(ADP-RIBOSE) POLYMERASE-1 PARP-1 ; DESIGN ; DISCOVERY ; CANCER
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研究方向Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:000602366100002
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/296377]  
专题新药研究国家重点实验室
通讯作者Miao, Ze-Hong; Yang, Chun-Hao
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Medica, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
2.Cent South Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Medica, State Key Lab Drug Res, 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.

入库方式： OAI收割

来源：上海药物研究所

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