Synthesis and biological evaluation of novel quinazoline-derived human Pin1 inhibitors

Lina Zhu; Jing Jin; Chang Liu; Chongjing Zhang; Yan Sun; Yanshen Guo; Decai Fu; Xiaoguang Chen; Bailing Xu

doi:10.1016/j.bmc.2011.03.058

Synthesis and biological evaluation of novel quinazoline-derived human Pin1 inhibitors

Bioorg Med Chem. 2011 May 1;19(9):2797-807. doi: 10.1016/j.bmc.2011.03.058. Epub 2011 Mar 29.

Authors

Lina Zhu¹, Jing Jin, Chang Liu, Chongjing Zhang, Yan Sun, Yanshen Guo, Decai Fu, Xiaoguang Chen, Bailing Xu

Affiliation

¹ Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

PMID: 21504850
DOI: 10.1016/j.bmc.2011.03.058

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Binding Sites
Catalytic Domain
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Humans
NIMA-Interacting Peptidylprolyl Isomerase
Peptidylprolyl Isomerase / antagonists & inhibitors*
Peptidylprolyl Isomerase / metabolism
Protein Structure, Tertiary
Quinazolines / chemical synthesis
Quinazolines / chemistry*
Quinazolines / pharmacology
Structure-Activity Relationship

Substances

Enzyme Inhibitors
NIMA-Interacting Peptidylprolyl Isomerase
Quinazolines
PIN1 protein, human
Peptidylprolyl Isomerase