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

doi:10.1016/j.bmcl.2020.127710

	Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors
	Xiang, Hao-Yue 1,2; Chen, Jian-Yang 2; Huan, Xia-Juan 2; Chen, Yi 3; Gao, Zhao-bing 4; Ding, Jian 2; Miao, Ze-Hong 2; Yang, Chun-Hao 2
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.