title: Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors.
abstract: We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Ling-xiao
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Xin-bo
authors.initials: XB
authors.lastname: Zhou
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Meng-liang
authors.initials: ML
authors.lastname: Xiao
authors.affiliation: Department of Traditional Chinese Materia Medica and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Traditional Chinese Materia Medica and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Traditional Chinese Materia Medica and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Wen-xia
authors.initials: WX
authors.lastname: Zhou
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China. Electronic address: wxkcaptain@aliyun.com.
authors.forename: Xiao-kui
authors.initials: XK
authors.lastname: Wang
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China. Electronic address: zhengzb@bmi.ac.cn.
authors.forename: Zhi-bing
authors.initials: ZB
authors.lastname: Zheng
authors.affiliation: Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010793:Phthalazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013876:Thiophenes; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: 4-(Thiophen-2-ylmethyl)-2H-phthalazin-1-ones; Antitumor; Biological evaluation; PARP-1 inhibitor; Synthesis