title: Synthesis and biological evaluation of novel quinazoline-derived human Pin1 inhibitors.
abstract: A series of novel 2,4-disubstituted quinazoline derivatives were prepared and their inhibitory activities on hPin1 were evaluated. Of all the synthesized compounds, eight compounds displayed inhibitory activities with IC(50) value at the level of 10(-6)mol/L. Preliminary structure-activity relationships were analyzed in details and the binding mode of the titled compounds was predicted using FlexX algorithm. The design and optimization of novel small molecule Pin1 inhibitors will be guided by the results of this report.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Chongjing
authors.initials: C
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yanshen
authors.initials: Y
authors.lastname: Guo
authors.forename: Decai
authors.initials: D
authors.lastname: Fu
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
authors.forename: Bailing
authors.initials: B
authors.lastname: Xu
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011799:Quinazolines; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase